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Huether KM, Lamb JM, Skelly J, Brigham E, McCormack MC, Bose S, Garrow OJ, Dixon AE. Omega-3 fatty acid intake potentiates bronchodilator response in patients with obesity and poorly controlled asthma. Respir Med 2025; 243:108131. [PMID: 40294806 DOI: 10.1016/j.rmed.2025.108131] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/04/2024] [Revised: 04/14/2025] [Accepted: 04/25/2025] [Indexed: 04/30/2025]
Abstract
RATIONALE Obesity is linked to poorly controlled asthma and may impair bronchodilator response. This study examines dietary factors affecting asthma symptoms, control, and lung function. METHODS In a multi-center, cross-sectional study of 102 individuals with obesity and poorly controlled asthma, we assessed dietary intake (Arizona Food Frequency Questionnaire), asthma symptoms and control (standardized questionnaires), and lung function (spirometry and bronchodilator response). Correlations between omega-3 and -6 fatty acids with asthma outcomes and lung function were examined using Pearson correlations and multivariate regression. RESULTS Median age was 56 (IQR 41-64) years, and median BMI was 37 (35-42) kg/m2. Fifty-four percent were African American and 75 % were female. Median total calorie intake was 2029 (1199-3837) kcal, median total omega-3 intake was 1.07 (0.63-2.04) g, and median omega-6 intake was 24.54 (13.31-45.35) g. No significant relationship was found between fatty acid intake and asthma symptoms, asthma control, or baseline lung function. However, percent bronchodilator response was positively correlated with omega-3 fatty acids (r = 0.273, p = 0.0074). After adjusting for caloric intake, for every 1 g increase in omega-3 intake, there was a 4 % increase in percent bronchodilator response. CONCLUSIONS Dietary intake of omega-3 fatty acids may influence bronchodilator response in patients with poorly controlled asthma and obesity. Interventions to improve overall dietary quality, such as increased omega-3 intake, may improve medication response in people with obesity and poorly controlled asthma. Future research is needed to better understand this association and determine if additional dietary factors might affect medication responses.
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Affiliation(s)
| | | | | | | | - Meredith C McCormack
- Center for Clinical Trials, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA.
| | - Sonali Bose
- Icahn School of Medicine, New York, NY, USA.
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2
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Takeda Y, Furuhashi M, Sakuma I, Hiramitsu S, Okada M, Ueda S, Kumashiro N, Sakurai M. Comparison of the effects of pemafibrate and omega-3 fatty acid ethyl on fatty liver index in patients with dyslipidemia treated with statin: a sub-analysis from the PROUD48 study. Front Endocrinol (Lausanne) 2025; 16:1549687. [PMID: 40375947 PMCID: PMC12078148 DOI: 10.3389/fendo.2025.1549687] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/21/2024] [Accepted: 04/02/2025] [Indexed: 05/18/2025] Open
Abstract
Background Fatty liver index (FLI) calculated by using body mass index, waist circumference and levels of triglycerides and γ-glutamyl transpeptidase is a noninvasive biomarker for diagnosis of metabolic dysfunction-associated steatotic liver disease (MASLD), which is one of the high-risk conditions of atherosclerotic cardiovascular diseases. To compare the effects of pemafibrate and omega-3 fatty acid ethyl on FLI, we conducted a sub-analysis study of the Pemafibrate Reduction of triglyceride-rich lipoproteins compared with Omega-3 fatty acid ethyl for Unmet needs in Dyslipidemic patients on target to apoB-48 (PROUD48) study. Methods 57 participants in the pemafibrate 0.4 mg per day treatment group (PEMA, men/women: 37/20, mean 64 years) and 60 participants in the omega-3 fatty acid ethyl 4 g per day treatment group (OMEGA-3, men/women: 35/25, mean 63 years) in the PROUD48 study were included in the present study. Changes in FLI and prevalence of MASLD from baseline to week 16 in PEMA and OMEGA-3 were investigated. Results Median FLI was significantly decreased by both PEMA (69.7 to 47.6, P < 0.001) and OMEGA-3 (64.8 to 59.5, P < 0.001). There was a significant difference in change in FLI between PEMA and OMEGA-3 (-18.3 ± 14.1 vs. -5.5 ± 9.4, P < 0.001). The proportions of MASLD estimated by FLI (baseline/week 16) in PEMA and OMEGA-3 were 93.0/68.4% (P = 0.002) and 90.0/85.0% (P = 0.582), respectively. Conclusions Pemafibrate is superior to omega-3 fatty acid ethyl in lowering effects of FLI and MASLD in patients with dyslipidemia receiving statin treatment, suggesting that pemafibrate is a beneficial agent for hypertriglyceridemia and reduction of the risk for MASLD.
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Affiliation(s)
- Yasutaka Takeda
- Department of Diabetology & Endocrinology, Kanazawa Medical University, Uchinada, Japan
| | - Masato Furuhashi
- Department of Cardiovascular, Renal and Metabolic Medicine, Sapporo Medical University School of Medicine, Sapporo, Japan
| | - Ichiro Sakuma
- Caress Sapporo Hokko Memorial Clinic, Sapporo, Japan
| | | | | | - Shinichiro Ueda
- Department of Clinical Pharmacology and Therapeutics, University of the Ryukyus, Nishihara, Japan
| | - Naoki Kumashiro
- Department of Diabetology & Endocrinology, Kanazawa Medical University, Uchinada, Japan
| | - Masaru Sakurai
- Department of Social and Environmental Medicine, Kanazawa Medical University, Uchinada, Japan
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Yang J, Shrestha A, Ramalingam L. Fishing for Solutions: How Pre-Conceptional Fish Oil Supplementation in Obese Fathers Reduces Risk of Non-Alcoholic Fatty Liver Disease in Offspring Mice. Mol Nutr Food Res 2025; 69:e202400452. [PMID: 39910853 PMCID: PMC11874265 DOI: 10.1002/mnfr.202400452] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/12/2024] [Revised: 11/30/2024] [Accepted: 01/03/2025] [Indexed: 02/07/2025]
Abstract
Metabolic dysfunction associated fatty liver disease (MAFLD) is a chronic condition with hepatic fat accumulation. The intergenerational effect of obesity has predominantly focused on mothers, with limited studies on paternal obesity. Nutritional intervention with fish oil (FO) has beneficial effects in reducing markers of obesity. We hypothesized that supplementing obese fathers with FO before conception could enhance the metabolic health of their offspring liver. Male mice were assigned to low-fat (LF), high fat (HF), or HF supplemented with FO for 10 weeks. Subsequently, these males were mated with females on a chow diet. Offspring were sacrificed at 8 weeks, and liver tissues were analyzed for gene expression and histology. Offspring body weight was not significantly impacted by paternal diet. However, male offspring of HF fathers had higher levels of markers of inflammation and fatty acid synthesis compared to offspring of LF fed fathers. Paternal FO supplementation significantly reduced fatty acid synthesis and glucose metabolism, while increasing fatty acid oxidation in male offspring, with a less pronounced effect in female offspring. These findings suggest that FO supplementation in obese fathers prior to conception attenuates the development of MAFLD in male offspring. This data underscores the significance of paternal nutritional intervention in promoting offspring health.
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Affiliation(s)
- Junhui Yang
- Department of Nutrition and Food StudiesSyracuse UniversitySyracuseNew YorkUSA
| | - Akriti Shrestha
- Department of Nutrition and Food StudiesSyracuse UniversitySyracuseNew YorkUSA
| | - Latha Ramalingam
- Department of Nutrition and Food StudiesSyracuse UniversitySyracuseNew YorkUSA
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4
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Ciobârcă D, Cătoi AF, Gavrilaș L, Banc R, Miere D, Filip L. Natural Bioactive Compounds in the Management of Type 2 Diabetes and Metabolic (Dysfunction)-Associated Steatotic Liver Disease. Pharmaceuticals (Basel) 2025; 18:279. [PMID: 40006091 PMCID: PMC11859434 DOI: 10.3390/ph18020279] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/18/2024] [Revised: 02/11/2025] [Accepted: 02/13/2025] [Indexed: 02/27/2025] Open
Abstract
Type 2 diabetes (T2D) and metabolic (dysfunction)-associated steatotic liver disease (MASLD) affect a growing number of individuals worldwide. T2D and MASLD often coexist and substantially elevate the risk of adverse hepatic and cardiovascular clinical outcomes. Several common pathogenetic mechanisms are responsible for T2D and MASLD onset and progression, including insulin resistance, oxidative stress, and low-grade inflammation, among others. The latter can also be induced by gut microbiota and its derived metabolites. Natural bioactive compounds (NBCs) have been reported for their therapeutic potential in both T2D and MASLD. A large amount of evidence obtained from clinical trials suggests that compounds like berberine, curcumin, soluble fibers, and omega-3 fatty acids exhibit significant hypoglycemic, hypolipidemic, and hepatoprotective activity in humans and may be employed as adjunct therapy in T2D and MASLD management. In this review, the role of the most studied NBCs in the management of T2D and MASLD is discussed, emphasizing recent clinical evidence supporting these compounds' efficacy and safety. Also, prebiotics that act against metabolic dysfunction by modulating gut microbiota are evaluated.
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Affiliation(s)
- Daniela Ciobârcă
- Department 2, Faculty of Nursing and Health Sciences, “Iuliu Hatieganu” University of Medicine and Pharmacy, 23 Gheorghe Marinescu Street, 400337 Cluj-Napoca, Romania; (D.C.); (L.G.)
| | - Adriana Florinela Cătoi
- Department of Pathophysiology, Faculty of Medicine, “Iuliu Hatieganu” University of Medicine and Pharmacy, 2-4 Victor Babes Street, 400012 Cluj-Napoca, Romania
| | - Laura Gavrilaș
- Department 2, Faculty of Nursing and Health Sciences, “Iuliu Hatieganu” University of Medicine and Pharmacy, 23 Gheorghe Marinescu Street, 400337 Cluj-Napoca, Romania; (D.C.); (L.G.)
| | - Roxana Banc
- Department of Bromatology, Hygiene, Nutrition, Faculty of Pharmacy, “Iuliu Hatieganu” University of Medicine and Pharmacy, 6 Louis Pasteur Street, 400349 Cluj-Napoca, Romania; (R.B.); (D.M.); (L.F.)
| | - Doina Miere
- Department of Bromatology, Hygiene, Nutrition, Faculty of Pharmacy, “Iuliu Hatieganu” University of Medicine and Pharmacy, 6 Louis Pasteur Street, 400349 Cluj-Napoca, Romania; (R.B.); (D.M.); (L.F.)
| | - Lorena Filip
- Department of Bromatology, Hygiene, Nutrition, Faculty of Pharmacy, “Iuliu Hatieganu” University of Medicine and Pharmacy, 6 Louis Pasteur Street, 400349 Cluj-Napoca, Romania; (R.B.); (D.M.); (L.F.)
- Academy of Romanian Scientists (AOSR), 3 Ilfov Street, 050044 Bucharest, Romania
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5
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Ando M, Lee-Okada HC, Yokomizo T. [Molecular Mechanisms by Which Polyunsaturated Fatty Acids Suppress the Pathogenesis and Progression of NAFLD]. YAKUGAKU ZASSHI 2025; 145:177-182. [PMID: 40024729 DOI: 10.1248/yakushi.24-00177-2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 03/04/2025]
Abstract
In recent years, the number of people suffering from lifestyle diseases such as hyperlipidemia and fatty liver disease has increased rapidly due to westernization of dietary patterns. Among fatty liver diseases, those that are not caused by alcohol are referred to as nonalcoholic fatty liver disease (NAFLD). Some NAFLD can progress to nonalcoholic steatohepatitis (NASH), and further progression of NAFLD can lead to cirrhosis and liver cancer. Although numerous studies have demonstrated the efficacy of dietary polyunsaturated fatty acids (PUFAs), particularly omega-3 PUFAs eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), against NAFLD, the detailed mechanisms by which these PUFAs exert their protective effects on the pathogenesis and progression of NAFLD are not well understood. Recent studies using knockout mouse models and genome-wide association studies have suggested a potential role for the enzymes responsible for the biosynthesis of PUFAs (FADS1, FADS2, ELOVL2, and ELOVL5) and their incorporation into phospholipids (LPCAT3/MBOAT5/LPLAT12 and LPIAT1/MBOAT7/LPLAT11) in the development of NAFLD. In this review, we summarize recent findings on the association of NAFLD and PUFAs with a focus on PUFA biosynthetic and metabolic enzymes to discuss the potential role of PUFAs in the prevention of NAFLD.
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Affiliation(s)
- Misa Ando
- Department of Biochemistry, Juntendo University Graduate School of Medicine
- Department of Breast Oncology, Juntendo University School of Medicine
| | | | - Takehiko Yokomizo
- Department of Biochemistry, Juntendo University Graduate School of Medicine
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Worthmann A, Ridder J, Piel SYL, Evangelakos I, Musfeldt M, Voß H, O'Farrell M, Fischer AW, Adak S, Sundd M, Siffeti H, Haumann F, Kloth K, Bierhals T, Heine M, Pertzborn P, Pauly M, Scholz JJ, Kundu S, Fuh MM, Neu A, Tödter K, Hempel M, Knippschild U, Semenkovich CF, Schlüter H, Heeren J, Scheja L, Kubisch C, Schlein C. Fatty acid synthesis suppresses dietary polyunsaturated fatty acid use. Nat Commun 2024; 15:45. [PMID: 38167725 PMCID: PMC10762034 DOI: 10.1038/s41467-023-44364-y] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/19/2023] [Accepted: 12/11/2023] [Indexed: 01/05/2024] Open
Abstract
Dietary polyunsaturated fatty acids (PUFA) are increasingly recognized for their health benefits, whereas a high production of endogenous fatty acids - a process called de novo lipogenesis (DNL) - is closely linked to metabolic diseases. Determinants of PUFA incorporation into complex lipids are insufficiently understood and may influence the onset and progression of metabolic diseases. Here we show that fatty acid synthase (FASN), the key enzyme of DNL, critically determines the use of dietary PUFA in mice and humans. Moreover, the combination of FASN inhibition and PUFA-supplementation decreases liver triacylglycerols (TAG) in mice fed with high-fat diet. Mechanistically, FASN inhibition causes higher PUFA uptake via the lysophosphatidylcholine transporter MFSD2A, and a diacylglycerol O-acyltransferase 2 (DGAT2)-dependent incorporation of PUFA into TAG. Overall, the outcome of PUFA supplementation may depend on the degree of endogenous DNL and combining PUFA supplementation and FASN inhibition might be a promising approach to target metabolic disease.
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Affiliation(s)
- Anna Worthmann
- Department of Biochemistry and Molecular Cell Biology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
| | - Julius Ridder
- Institute of Human Genetics, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
| | - Sharlaine Y L Piel
- Institute of Human Genetics, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
| | - Ioannis Evangelakos
- Institute of Human Genetics, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
| | - Melina Musfeldt
- Institute of Human Genetics, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
| | - Hannah Voß
- Section / Core Facility Mass Spectrometry and Proteomics, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
| | - Marie O'Farrell
- Sagimet Biosciences Inc., 155 Bovet Rd., San Mateo, CA, 94402, USA
| | - Alexander W Fischer
- Department of Biochemistry and Molecular Cell Biology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
- Department of Molecular Metabolism, Harvard T. H. Chan School of Public Health, Harvard University, Boston, MA, USA
- Department of Cell Biology, Harvard Medical School, Boston, MA, USA
| | - Sangeeta Adak
- Division of Endocrinology, Metabolism & Lipid Research, Department of Medicine, Washington University, St. Louis, MO, USA
| | - Monica Sundd
- National Institute of Immunology, New Delhi, India
| | - Hasibullah Siffeti
- Institute of Human Genetics, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
| | - Friederike Haumann
- Institute of Human Genetics, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
| | - Katja Kloth
- Institute of Human Genetics, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
| | - Tatjana Bierhals
- Institute of Human Genetics, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
| | - Markus Heine
- Department of Biochemistry and Molecular Cell Biology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
| | - Paul Pertzborn
- Department of Biochemistry and Molecular Cell Biology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
| | - Mira Pauly
- Department of Biochemistry and Molecular Cell Biology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
| | - Julia-Josefine Scholz
- Institute of Human Genetics, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
| | - Suman Kundu
- Department of Biochemistry, University of Delhi South Campus, New Delhi 110021 and Department of Biological Sciences, Birla Institute of Technology and Science Pilani, K K Birla Goa Campus, Goa, 403726, India
| | - Marceline M Fuh
- Department of Biochemistry and Molecular Cell Biology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
| | - Axel Neu
- Department of Pediatrics, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
| | - Klaus Tödter
- Department of Biochemistry and Molecular Cell Biology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
| | - Maja Hempel
- Institute of Human Genetics, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
- Institute of Human Genetics, University Hospital Heidelberg, Im Neuenheimer Feld 440, 69120, Heidelberg, Germany
| | - Uwe Knippschild
- Department of General and Visceral Surgery, University Hospital Ulm, Ulm, Germany
| | - Clay F Semenkovich
- Division of Endocrinology, Metabolism & Lipid Research, Department of Medicine, Washington University, St. Louis, MO, USA
| | - Hartmut Schlüter
- Section / Core Facility Mass Spectrometry and Proteomics, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
| | - Joerg Heeren
- Department of Biochemistry and Molecular Cell Biology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
| | - Ludger Scheja
- Department of Biochemistry and Molecular Cell Biology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
| | - Christian Kubisch
- Institute of Human Genetics, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
| | - Christian Schlein
- Institute of Human Genetics, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
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Hao L, Chen CY, Nie YH, Kaliannan K, Kang JX. Differential Interventional Effects of Omega-6 and Omega-3 Polyunsaturated Fatty Acids on High Fat Diet-Induced Obesity and Hepatic Pathology. Int J Mol Sci 2023; 24:17261. [PMID: 38139090 PMCID: PMC10743920 DOI: 10.3390/ijms242417261] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/30/2023] [Revised: 12/01/2023] [Accepted: 12/04/2023] [Indexed: 12/24/2023] Open
Abstract
Current Dietary Guidelines for Americans recommend replacing saturated fat (SFA) intake with polyunsaturated fatty acids (PUFAs) and monosaturated fatty acids (MUFAs) but do not specify the type of PUFAs, which consist of two functionally distinct classes: omega-6 (n-6) and omega-3 (n-3) PUFAs. Given that modern Western diets are already rich in n-6 PUFAs and the risk of chronic disease remains high today, we hypothesized that increased intake of n-3 PUFAs, rather than n-6 PUFAs, would be a beneficial intervention against obesity and related liver diseases caused by high-fat diets. To test this hypothesis, we fed C57BL/6J mice with a high-fat diet (HF) for 10 weeks to induce obesity, then divided the obese mice into three groups and continued feeding for another 10 weeks with one of the following three diets: HF, HF+n-6 (substituted half of SFA with n-6 PUFAs), and HF+n-3 (substituted half of SFA with n-3 PUFAs), followed by assessment of body weight, fat mass, insulin sensitivity, hepatic pathology, and lipogenesis. Interestingly, we found that the HF+n-6 group, like the HF group, had a continuous increase in body weight and fat mass, while the HF+n-3 group had a significant decrease in body weight and fat mass, although all groups had the same calorie intake. Accordingly, insulin resistance and fatty liver pathology (steatosis and fat levels) were evident in the HF+n-6 and HF groups but barely seen in the HF+n-3 group. Furthermore, the expression of lipogenesis-related genes in the liver was upregulated in the HF+n-6 group but downregulated in the HF+n-3 group. Our findings demonstrate that n-6 PUFAs and n-3 PUFAs have differential effects on obesity and fatty liver disease and highlight the importance of increasing n-3 PUFAs and reducing n-6 PUFAs (balancing the n-6/n-3 ratio) in clinical interventions and dietary guidelines for the management of obesity and related diseases.
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Affiliation(s)
- Lei Hao
- Laboratory for Lipid Medicine and Technology (LLMT), Department of Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02129, USA; (L.H.); (C.-Y.C.)
- Department of Nursing and Allied Health Professions, Indiana University of Pennsylvania, Indiana, PA 15705, USA
| | - Chih-Yu Chen
- Laboratory for Lipid Medicine and Technology (LLMT), Department of Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02129, USA; (L.H.); (C.-Y.C.)
- Emory School of Medicine, Emory University, Atlanta, GA 30322, USA
| | - Yong-Hui Nie
- Laboratory for Lipid Medicine and Technology (LLMT), Department of Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02129, USA; (L.H.); (C.-Y.C.)
| | - Kanakaraju Kaliannan
- Laboratory for Lipid Medicine and Technology (LLMT), Department of Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02129, USA; (L.H.); (C.-Y.C.)
| | - Jing X. Kang
- Laboratory for Lipid Medicine and Technology (LLMT), Department of Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02129, USA; (L.H.); (C.-Y.C.)
- Omega-3 and Global Health Institute, Boston, MA 02129, USA
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Das A, Tang YLM, Althumiri NA, Garcia-Larsen V, Schattenberg JM, Alqahtani SA. Fatty acid composition but not quantity is an important indicator of non-alcoholic fatty liver disease: a systematic review. Eur J Clin Nutr 2023; 77:1113-1129. [PMID: 37661229 DOI: 10.1038/s41430-023-01335-2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/03/2023] [Revised: 08/14/2023] [Accepted: 08/17/2023] [Indexed: 09/05/2023]
Abstract
BACKGROUND There is still paucity on the effects of dietary and supplemental fatty acid on non-alcoholic fatty liver disease (NAFLD). The aim of this review is to systematically review and summarise the effect of fatty acids intake on liver-related outcomes in adult patients with NAFLD. METHODS The review was conducted using Cochrane CENTRAL Library, Scopus, Embase, MEDLINE, PubMed, and Web of Science. A total of 2786 records were identified, and of these, 36 studies (31 were randomised control trials (RCTs), and 5 were case-control studies) were included. Quality assessment was conducted using the Revised Cochrane Risk of Bias tool and Joanna Briggs Institute checklists. RESULTS Of 36 articles, 79% of RCTs and 66% of case-control studies had a low risk of bias. Potential heterogeneity has been observed in assessment of liver-related outcomes. According to the RCTs, there was moderate evidence (3/6 studies) that a diet characterised by a high MUFA, PUFA and low SFA showed reduced liver fat and stiffness. The using of culinary fats that are high in MUFA (4/6 studies) reduces liver steatosis. n-3 PUFA supplementation in combination with a hypocaloric or heart healthy diet with a low SFA improved liver enzyme level (5/14 studies) and steatosis score (3/14 studies). CONCLUSIONS Effects on NAFLD parameters, including liver fat content (assessed via magnetic resonance imaging/spectroscopy), stiffness and steatosis score (assessed by ultrasonography), were primarily related to fatty acid composition independent of energy intake. Further investigation is needed to determine the mechanism of specific fatty acid on the accumulation of liver fat.
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Affiliation(s)
- Arpita Das
- Department of Nutrition and Dietetics, Charles Perkins Centre, The University of Sydney, Sydney, NSW, Australia.
| | - Yu Lung Malcolm Tang
- Department of Nutrition and Dietetics, Charles Perkins Centre, The University of Sydney, Sydney, NSW, Australia
| | | | - Vanessa Garcia-Larsen
- Program in Human Nutrition, Department of International Health, The Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA
| | - Jörn M Schattenberg
- Metabolic Liver Research Program, I. Department of Medicine, University Medical Centre, Mainz, Germany
| | - Saleh A Alqahtani
- Division of Gastroenterology and Hepatology, Johns Hopkins University, Baltimore, MD, USA
- Liver Transplantation Centre, King Faisal Specialist Hospital & Research Centre, Riyadh, Saudi Arabia
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Reddy A, Gatta PD, Mason S, Nicoll AJ, Ryan M, Itsiopoulos C, Abbott G, Johnson NA, Sood S, Roberts SK, George ES, Tierney AC. Adherence to a Mediterranean diet may improve serum adiponectin in adults with nonalcoholic fatty liver disease: The MEDINA randomized controlled trial. Nutr Res 2023; 119:98-108. [PMID: 37801761 DOI: 10.1016/j.nutres.2023.09.005] [Citation(s) in RCA: 9] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/01/2023] [Revised: 09/06/2023] [Accepted: 09/07/2023] [Indexed: 10/08/2023]
Abstract
Nonalcoholic fatty liver disease (NAFLD) affects approximately 30% of adults worldwide, with chronic low-grade inflammation being a key pathophysiological feature of progression. The Mediterranean diet (MedDiet) is recognized for improving metabolic and hepatic outcomes in people with diabetes and NAFLD, in part, via anti-inflammatory properties. The aim of this study was to determine the effect of an ad libitum MedDiet versus low-fat diet (LFD) on inflammatory markers in adults with NAFLD. It was hypothesized that the MedDiet, and its individual components, would improve inflammation. This multicenter, randomized controlled trial, randomized participants to a MedDiet or LFD intervention for 12 weeks. Primary outcomes included change from baseline to 12 weeks for serum high-sensitivity C-reactive protein, interleukin-6, tumor necrosis factor-α, adiponectin, leptin, and resistin. Forty-two participants (60% female; age 52.3 ± 12.6 years; body mass index, 32.2 ± 6.2 kg/m²) were randomized to the MedDiet (n = 19) or low-fat diet (n = 23). At 12 weeks, the LFD showed a greater decrease in leptin compared with the MedDiet (-1.20 ± 3.9 ng/mL vs 0.64 ± 3.5 ng/mL, P = .010). Adiponectin significantly improved within the MedDiet (13.7 ± 9.2 µg/mL to 17.0 ± 12.5 µg/mL, P = .016), but not within the LFD group. No statistically significant changes were observed for other inflammatory markers following the MedDiet or LFD. Adherence to the MedDiet significantly improved in both study arms, although greater improvements were seen in the MedDiet group. Adiponectin significantly improved following a Mediterranean diet intervention, in the absence of weight loss. The low-fat diet did not elicit improvements in inflammatory markers. High-quality clinical trials appropriately powered to inflammatory markers are required in this population.
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Affiliation(s)
- Anjana Reddy
- School of Allied Health, Human Services and Sport, La Trobe University, Australia; Monash Centre for Health Research and Implementation, School of Public Health and Preventative Medicine, Monash University, Melbourne, VIC, Australia
| | - Paul Della Gatta
- Institute for Physical Activity and Nutrition, School of Exercise and Nutrition Sciences, Deakin University, Geelong, Australia
| | - Shaun Mason
- Institute for Physical Activity and Nutrition, School of Exercise and Nutrition Sciences, Deakin University, Geelong, Australia
| | - Amanda J Nicoll
- Department of Gastroenterology, Eastern Health, Box Hill, Australia
| | - Marno Ryan
- Department of Gastroenterology and Hepatology, St Vincent's Hospital, Fitzroy, Australia
| | - Catherine Itsiopoulos
- School of Allied Health, Human Services and Sport, La Trobe University, Australia; School of Health and Biomedical Sciences, RMIT University, Melbourne, Australia
| | - Gavin Abbott
- Monash Centre for Health Research and Implementation, School of Public Health and Preventative Medicine, Monash University, Melbourne, VIC, Australia
| | - Nathan A Johnson
- The Boden Collaboration for Obesity, Nutrition, Exercise and Eating Disorders, The University of Sydney, Sydney, New South Wales, Australia
| | - Siddharth Sood
- Department of Gastroenterology, Melbourne Health, Melbourne, Australia; Department of Medicine, University of Melbourne, Parkville, Australia
| | - Stuart K Roberts
- Department of Gastroenterology, Alfred Health, Prahran, Australia; Central Clinical School, Monash University, Clayton, Australia
| | - Elena S George
- School of Allied Health, Human Services and Sport, La Trobe University, Australia; Institute for Physical Activity and Nutrition, School of Exercise and Nutrition Sciences, Deakin University, Geelong, Australia.
| | - Audrey C Tierney
- School of Allied Health, Human Services and Sport, La Trobe University, Australia; School of Allied Health, Health Implementation Science and Technology Research Cluster, Health Research Institute, University of Limerick, Ireland
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Jafari N, Bahreini N, Dehghani A, Lak Y, Mirmohammadali SN, Samavat S, Shami A, Karimizand M, Goudarzi MA, Asbaghi O. The effects of purslane consumption on lipid profile and C-reactive protein: A systematic review and dose-response meta-analysis. Food Sci Nutr 2023; 11:6728-6748. [PMID: 37970383 PMCID: PMC10630813 DOI: 10.1002/fsn3.3555] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/21/2023] [Revised: 06/21/2023] [Accepted: 06/24/2023] [Indexed: 11/17/2023] Open
Abstract
Earlier investigations into the impact of purslane, Portulaca oleracea, on lipid profile and C-reactive protein (CRP) produced contradictory findings. The effect of purslane consumption on lipid profiles and CRP was assessed in this comprehensive review and meta-analysis. We conducted a thorough literature search in online databases, including PubMed, Scopus, the Cochrane library, and ISI Web of Science to find relevant randomized controlled trials up to June 2023. By incorporating 14 effect sizes from 13 RCTs, we were able to show that purslane consumption significantly decreases serum triglyceride (TG) (WMD: -16.72, 95% CI: -22.49, -10.96 mg/dL, p < .001), total cholesterol (TC) (WMD: -9.97, 95% CI: -19.86, -0.07 mg/dL, p = .048), and CRP (WMD: -1.22, 95% CI: -1.63, -0.80 mg/L, p < .001) levels in patients compared to the control group. In addition, purslane consumption significantly increases high-density lipoprotein (HDL-C) (WMD: 4.09, 95% CI: 1.77, 6.41 mg/dL, p = .001) levels. However, purslane consumption did not affect low-density lipoprotein (LDL-C) levels. According to a suggested optimal dosage, purslane consumption is considered to be safe up to 30 g/day. Purslane consumption can significantly improve cardiovascular health by improving lipid profile and inflammation status.
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Affiliation(s)
- Naser Jafari
- University of Applied Science and Technology – Allameh Tabarsi CenterTehranIran
| | - Nazgol Bahreini
- Student Research CommitteeTabriz University of Medical SciencesTabrizIran
- Nutrition Research Center, School of Nutrition and Food SciencesTabriz University of Medical SciencesTabrizIran
| | - Azadeh Dehghani
- Nutrition Research Center, Department of Community Nutrition, Faculty of Nutrition and Food ScienceTabriz University of Medical SciencesTabrizIran
| | | | | | - Simin Samavat
- Department of Cellular and Molecular Nutrition, School of Nutrition Sciences and DieteticsTehran University of Medical SciencesTehranIran
| | - Amirhossein Shami
- Student of Cellular Molecular Biology, Faculty of ScienceArdabil Branch, Islamic Azad UniversityArdabilIran
| | | | | | - Omid Asbaghi
- Cancer Research CenterShahid Beheshti University of Medical sciencesTehranIran
- Student Research CommitteeShahid Beheshti University of Medical SciencesTehranIran
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11
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Barroso LN, Salarini J, Leite NC, Villela-Nogueira CA, Dávalos A, Carmo MDGT, Ferreira Peres WA. Effect of fish oil supplementation on the concentration of miRNA-122, FGF-21 and liver fibrosis in patients with NAFLD: Study protocol for a randomized, double-blind and placebo-controlled clinical trial. Clin Nutr ESPEN 2023; 57:117-125. [PMID: 37739645 DOI: 10.1016/j.clnesp.2023.06.027] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/17/2023] [Revised: 06/22/2023] [Accepted: 06/25/2023] [Indexed: 09/24/2023]
Abstract
BACKGROUND & AIMS To date, no specific drugs are available for non-alcoholic fatty liver disease (NAFLD), though the effect of fish oil supplementation on improving fibrosis in patients with NAFLD has been evaluated. N-3 polyunsaturated fatty acids (n-3 PUFA) may modulate the concentration of microRNAs (miRNAs) and fibroblast growth factor (FGF)-21, which have been identified as non-invasive markers of liver fibrosis. The present study aims to evaluate whether n-3 PUFA supplementation can modulate miRNA-122 and FGF-21 and improve liver fibrosis and steatosis, measured by transient hepatic elastography (THE), in individuals with NAFLD. METHODS A randomized, double-blind, placebo-controlled clinical trial will be conducted to evaluate the effect of 4 g/day supplementation of fish oil (2100 mg EPA and 924 mg DHA) in patients with NAFLD over a 6-month period. Fifty-two patients aged >19 years will be randomly assigned to either a placebo (olive oil) or treatment (fish oil) group. Anthropometric data, food intake, physical activity, body composition, resting energy expenditure (evaluated using indirect calorimetry), liver enzymes, platelets, lipids and glucose profile, inflammatory markers (such as C-reactive protein, neutrophil/lymphocyte, platelet/lymphocyte, and monocyte/lymphocyte ratios), miRNA-122 and FGF-21 concentration, and incorporation of fatty acids into the erythrocyte membrane (analyzed using gas chromatography) as well as the degree of liver fibrosis and steatosis assessed using THE (Fibroscan® Touch 502, Paris, France) and liver biomarkers Steato-Brazilian Longitudinal Study of Adult Health, Fatty Liver Index, NAFLD Fibrosis Score, Fibrosis-4 score, and FibroScan-AST score will be evaluated at the beginning and end of the treatment. Continuous variables with normal distribution will be compared between placebo and intervention groups using Student's T test for independent samples; continuous non-parametric variables will be compared using Dunn or Mann-Whitney test. Associations between categorical variables will be analyzed using the chi-square test, and within-group differences will be evaluated using the Wilcoxon signed-ranks test. The criterion for determining significance will be set at 5%. CONCLUSION The present study protocol will investigate the supplementation of EPA-rich fish oil as an alternative treatment for NAFLD and its feasibility in affecting the concentration of miRNA-122 and FGF-21 markers. Its findings will offer valuable contributions to the literature. REGISTRATION ReBEC number RBR-8dp876.
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Affiliation(s)
- Lygia N Barroso
- Josué de Castro Nutrition Institute, Federal University of Rio de Janeiro, Carlos Chagas Filho Avenue, 367/CCS - Block J2, University City-Ilha Do Fundão, Rio de Janeiro, RJ, Brazil; School of (M)edicine, Clementino Fraga Filho University Hospital, Federal University of Rio de Janeiro, Prof. Rodolpho Paulo Rocco Street, 255 - University City-Ilha Do Fundão, Rio de Janeiro, RJ, Brazil
| | - Jessica Salarini
- Josué de Castro Nutrition Institute, Federal University of Rio de Janeiro, Carlos Chagas Filho Avenue, 367/CCS - Block J2, University City-Ilha Do Fundão, Rio de Janeiro, RJ, Brazil; School of (M)edicine, Clementino Fraga Filho University Hospital, Federal University of Rio de Janeiro, Prof. Rodolpho Paulo Rocco Street, 255 - University City-Ilha Do Fundão, Rio de Janeiro, RJ, Brazil
| | - Nathalie Carvalho Leite
- School of (M)edicine, Clementino Fraga Filho University Hospital, Federal University of Rio de Janeiro, Prof. Rodolpho Paulo Rocco Street, 255 - University City-Ilha Do Fundão, Rio de Janeiro, RJ, Brazil
| | - Cristiane A Villela-Nogueira
- School of (M)edicine, Clementino Fraga Filho University Hospital, Federal University of Rio de Janeiro, Prof. Rodolpho Paulo Rocco Street, 255 - University City-Ilha Do Fundão, Rio de Janeiro, RJ, Brazil
| | - Alberto Dávalos
- Laboratory of Epigenetics of Lipid Metabolism, Madrid Institute for Advanced Studies (IMDEA), Madrid, Spain
| | - Maria das Graças Tavares Carmo
- Josué de Castro Nutrition Institute, Federal University of Rio de Janeiro, Carlos Chagas Filho Avenue, 367/CCS - Block J2, University City-Ilha Do Fundão, Rio de Janeiro, RJ, Brazil
| | - Wilza Arantes Ferreira Peres
- Josué de Castro Nutrition Institute, Federal University of Rio de Janeiro, Carlos Chagas Filho Avenue, 367/CCS - Block J2, University City-Ilha Do Fundão, Rio de Janeiro, RJ, Brazil.
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12
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Vachliotis ID, Polyzos SA. The Role of Tumor Necrosis Factor-Alpha in the Pathogenesis and Treatment of Nonalcoholic Fatty Liver Disease. Curr Obes Rep 2023; 12:191-206. [PMID: 37407724 PMCID: PMC10482776 DOI: 10.1007/s13679-023-00519-y] [Citation(s) in RCA: 33] [Impact Index Per Article: 16.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 06/20/2023] [Indexed: 07/07/2023]
Abstract
PURPOSE OF REVIEW To summarize experimental and clinical evidence on the association between tumor necrosis factor-α (TNF-α) and nonalcoholic fatty liver disease (NAFLD) and discuss potential treatment considerations. RECENT FINDINGS Experimental evidence suggests that TNF-α is a cytokine with a critical role in the pathogenesis of NAFLD. Although, the production of TNF-α may be an early event during the course of nonalcoholic fatty liver (NAFL), TNF-α may play a more substantial role in the pathogenesis of nonalcoholic steatohepatitis (NASH) and NAFLD-associated fibrosis. Moreover, TNF-α may potentiate hepatic insulin resistance, thus interconnecting inflammatory with metabolic signals and possibly contributing to the development of NAFLD-related comorbidities, including cardiovascular disease, hepatocellular carcinoma, and extra-hepatic malignancies. In clinical terms, TNF-α is probably associated with the severity of NAFLD; circulating TNF-α gradually increases from controls to patients with NAFL, and then, to patients with NASH. Given this potential association, various therapeutic interventions (obeticholic acid, peroxisome proliferator-activated receptors, sodium-glucose co-transporter 2 inhibitors, glucagon-like peptide-1 receptor agonists, probiotics, synbiotics, rifaximin, vitamin E, pentoxifylline, ursodeoxycholic acid, fibroblast growth factor-21, n-3 polyunsaturated fatty acids, statins, angiotensin receptor blockers) have been evaluated for their effect on TNF-α and NAFLD. Interestingly, anti-TNF biologics have shown favorable metabolic and hepatic effects, which may open a possible therapeutic window for the management of advanced NAFLD. The potential key pathogenic role of TNF-α in NAFLD warrants further investigation and may have important diagnostic and therapeutic implications.
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Affiliation(s)
- Ilias D. Vachliotis
- First Department of Pharmacology, Medical School, Aristotle University of Thessaloniki, 54124 Thessaloniki, Greece
- Second Department of Internal Medicine, 424 General Military Hospital, Thessaloniki, Greece
| | - Stergios A. Polyzos
- First Department of Pharmacology, Medical School, Aristotle University of Thessaloniki, 54124 Thessaloniki, Greece
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13
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Anwar SD, Foster C, Ashraf A. Lipid Disorders and Metabolic-Associated Fatty Liver Disease. Endocrinol Metab Clin North Am 2023; 52:445-457. [PMID: 37495336 DOI: 10.1016/j.ecl.2023.01.003] [Citation(s) in RCA: 15] [Impact Index Per Article: 7.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/28/2023]
Abstract
Dyslipidemia has been linked metabolic-associated fatty liver disease (MAFLD). Several genes and transcription factors involved in lipid metabolism can increase susceptibility to MAFLD. Multiple parallel 'hits' have been proposed for developing hepatic steatosis, NASH, and MAFLD, including insulin resistance and subsequent free fatty acid excess, de novo lipogenesis, and excessive hepatic triglyceride and cholesterol deposition in the liver. This lead to defective beta-oxidation in the mitochondria and VLDL export and increased inflammation. Given the significant cardiovascular risk, dyslipidemia associated with MAFLD should be managed by lifestyle changes and lipid-lowering agents such as statins, fenofibrate, and omega-3 fatty acids, with judicious use of insulin-sensitizing agents, and adequate control of dysglycemia.
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Affiliation(s)
- Shima Dowla Anwar
- Department of Pediatrics, Boston Children Hospital, Harvard Medical School, Boston, MA, USA
| | - Christy Foster
- University of Alabama at Birmingham, 1601, 4th Avenue South, CPP M 30, Birmingham, AL 35233, USA
| | - Ambika Ashraf
- University of Alabama at Birmingham, 1601, 4th Avenue South, CPP M 30, Birmingham, AL 35233, USA.
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Dong Y, Wei Y, Wang L, Song K, Zhang C, Lu K, Rahimnejad S. Dietary n-3/n-6 polyunsaturated fatty acid ratio modulates growth performance in spotted seabass ( Lateolabrax maculatus) through regulating lipid metabolism, hepatic antioxidant capacity and intestinal health. ANIMAL NUTRITION (ZHONGGUO XU MU SHOU YI XUE HUI) 2023; 14:20-31. [PMID: 37234947 PMCID: PMC10208799 DOI: 10.1016/j.aninu.2023.04.005] [Citation(s) in RCA: 11] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 08/11/2022] [Revised: 01/12/2023] [Accepted: 04/04/2023] [Indexed: 05/28/2023]
Abstract
An 8-week feeding experiment was carried out to explore the effects of dietary n-3/n-6 polyunsaturated fatty acid (PUFA) ratio on growth performance, lipid metabolism, hepatic antioxidant status, and gut flora of spotted seabass (Lateolabrax maculatus). Six experimental diets were formulated to contain different levels of two purified oil sources including docosahexaenoic and eicosapentaenoic acids enriched oil (n-3) and linoleic acid-enriched oil (n-6) leading to n-3/n-6 PUFA ratios of 0.04, 0.35, 0.66, 1.35, 2.45 and 16.17. Each diet was fed to triplicate groups of juvenile L. maculatus (11.06 ± 0.20 g, 30 fish/tank). Final body weight (FBW), weight gain (WG), specific growth rates (SGR), protein efficiency ratio (PER) and feed utilization efficiency increased as n-3/n-6 PUFA ratio increased up to a certain level, and then decreased thereafter. Fish fed the diet with n-3/n-6 PUFA ratio of 0.66 exhibited the highest FBW, WG, SGR and PER and the lowest feed conversion ratio. Lower n-3/n-6 PUFA ratios induced up-regulated expression of lipid synthesis-related genes (fas, acc2 and srebp-1c) and down-regulated expression of lipolysis related genes (atgl, pparα, cpt-1 and aox). Higher expression of lipolysis-related genes (atgl, pparα and cpt-1) was recorded at moderate n-3/n-6 PUFA ratios (0.66 to 1.35). Moreover, inappropriate n-3/n-6 PUFA ratios triggered up-regulation of pro-inflammatory genes (il-6 and tnf-α) and down-regulation of anti-inflammatory genes (il-4 and il-10) in the intestine. The diet with n-3/n-6 PUFA ratio of 0.66 inhibited intestine inflammation, improved intestinal flora richness, increased the abundance of beneficial bacteria such as Lactobacillus, Alloprevotella and Ruminococcus, and reduced the abundance of harmful bacteria including Escherichia-Shigella and Enterococcus. In summary, it could be suggested that a dietary n-3/n-6 PUFA ratio of 0.66 can improve growth performance and feed utilization in L. maculatus, as is deemed to be mediated through regulation of lipid metabolism and intestinal flora.
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Affiliation(s)
- Yanzou Dong
- Key Laboratory of Healthy Mariculture for the East China Sea, Ministry of Agriculture and Rural Affairs, Fisheries College, Jimei University, Xiamen 361021, China
| | - Yu Wei
- Key Laboratory of Healthy Mariculture for the East China Sea, Ministry of Agriculture and Rural Affairs, Fisheries College, Jimei University, Xiamen 361021, China
| | - Ling Wang
- Key Laboratory of Healthy Mariculture for the East China Sea, Ministry of Agriculture and Rural Affairs, Fisheries College, Jimei University, Xiamen 361021, China
| | - Kai Song
- Key Laboratory of Healthy Mariculture for the East China Sea, Ministry of Agriculture and Rural Affairs, Fisheries College, Jimei University, Xiamen 361021, China
| | - Chunxiao Zhang
- Key Laboratory of Healthy Mariculture for the East China Sea, Ministry of Agriculture and Rural Affairs, Fisheries College, Jimei University, Xiamen 361021, China
| | - Kangle Lu
- Key Laboratory of Healthy Mariculture for the East China Sea, Ministry of Agriculture and Rural Affairs, Fisheries College, Jimei University, Xiamen 361021, China
| | - Samad Rahimnejad
- Faculty of Fisheries and Protection of Waters, University of South Bohemia in České Budějovice, South Bohemian Research Centre of Aquaculture and Biodiversity of Hydrocenoses, Vodňany, Zátiší 728, Vodňany 389 25, Czech Republic
- Fish Innate Immune System Group, Department of Cell Biology and Histology, Faculty of Biology, Regional Campus of International Excellence “Campus Mare Nostrum”, University of Murcia, Murcia 30100, Spain
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15
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Khorshidi M, Hazaveh ZS, Alimohammadi-kamalabadi M, Jamshidi S, Moghaddam OM, Olang B, Hatefi S, Hosseini A, Jamilian P, Zarezadeh M, Kohansal P, Heshmati J, Jamilian P, Sayyari A. Effect of omega-3 supplementation on lipid profile in children and adolescents: a systematic review and meta-analysis of randomized clinical trials. Nutr J 2023; 22:9. [PMID: 36765362 PMCID: PMC9912483 DOI: 10.1186/s12937-022-00826-5] [Citation(s) in RCA: 6] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/24/2021] [Accepted: 11/10/2022] [Indexed: 02/12/2023] Open
Abstract
PURPOSE Dyslipidemia is considered as a known risk factor for cardiovascular disease. Yet various trials with wide ranges of doses and durations have reported contradictory results. We undertook this meta-analysis of randomized controlled trials (RCTs) to determine whether omega-3 supplementation can affect lipid profile in children and adolescents. METHODS Cochrane Library, Embase, PubMed, and Scopus databases were searched up to March 2021. Meta-analysis was performed using random-effect method. Effect size was expressed as weighted mean difference (WMD) and 95% confidence interval (CI). Heterogeneity was assessed using the I2 index. In order to identification of potential sources of heterogeneity, predefined subgroup and meta-regression analysis was conducted. RESULTS A total of 14 RCTs with 15 data sets were included. Based on the combination of effect sizes, there was a significant reduction in TG levels (WMD: -15.71 mg/dl, 95% CI: -25.76 to -5.65, P=0.002), with remarkable heterogeneity (I2=88.3%, P<0.001). However, subgroup analysis revealed that omega-3 supplementation significantly decreased TG only in studies conducted on participants ≤13 years old (WMD=-25.09, 95% CI: -43.29 to -6.90, P=0.007), (I2=84.6%, P<0.001) and those with hypertriglyceridemia (WMD=-28.26, 95% CI: -39.12 to -17.41, P<0.001), (I2=0.0%, P=0.934). Omega-3 supplementation had no significant effect on total cholesterol, HDL, and LDL levels. Also, results of nonlinear analysis showed significant effect of treatment duration on HDL status (Pnon-linearity=0.047). CONCLUSION Omega-3 supplementation may significantly reduce TG levels in younger children and those with hypertriglyceridemia. Also, based on the HDL-related results, clinical trials with longer duration of intervention are recommended in this population.
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Affiliation(s)
- Masoud Khorshidi
- grid.411600.2Pediatric Gastroenterology, Hepatology and Nutrition Research Center, Research Institute for Children’s Health, Shahid Beheshti University of Medical Sciences, Tehran, Iran ,grid.411746.10000 0004 4911 7066Department of Nutrition, School of Public Health, Iran University of Medical Sciences, Tehran, Iran
| | - Zohreh Sajadi Hazaveh
- grid.411600.2Cancer Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Malek Alimohammadi-kamalabadi
- grid.411705.60000 0001 0166 0922Department of Clinical Nutrition, School of nutrition sciences and dietetics, Tehran University of Medical Sciences, Tehran, Iran
| | - Sanaz Jamshidi
- grid.411746.10000 0004 4911 7066Department of Nutrition, School of Public Health, Iran University of Medical Sciences, Tehran, Iran
| | - Omid Moradi Moghaddam
- grid.411746.10000 0004 4911 7066Trauma and Injury Research Center, Critical Care Medicine Department, Iran University of Medical Sciences, Tehran, Iran
| | - Beheshteh Olang
- grid.411600.2Pediatric Gastroenterology, Hepatology and Nutrition Research Center, Research Institute for Children’s Health, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Sayeh Hatefi
- grid.411600.2Pediatric Gastroenterology, Hepatology and Nutrition Research Center, Research Institute for Children’s Health, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Amirhossein Hosseini
- grid.411600.2Pediatric Gastroenterology, Hepatology and Nutrition Research Center, Research Institute for Children’s Health, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Parsa Jamilian
- grid.9757.c0000 0004 0415 6205Keele Medical School, Keele University, Staffordshire, UK
| | - Meysam Zarezadeh
- grid.412888.f0000 0001 2174 8913Student Research Committee, Tabriz University of Medical Sciences, Tabriz, Iran ,grid.412888.f0000 0001 2174 8913Nutrition Research Center, School of Nutrition and Food Sciences, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Parichehr Kohansal
- grid.411463.50000 0001 0706 2472Department of Toxicology & Pharmacology, Faculty of Pharmacy, Tehran Medical Sciences, Islamic Azad University, Tehran, Iran
| | - Javad Heshmati
- grid.412112.50000 0001 2012 5829Songhor Healthcare Center, Kermanshah University of Medical Sciences, Kermanshah, Iran
| | - Parmida Jamilian
- grid.9757.c0000 0004 0415 6205School of Pharmacy and Bio engineering, Keele University, Staffordshire, UK
| | - Aliakbar Sayyari
- Pediatric Gastroenterology, Hepatology and Nutrition Research Center, Research Institute for Children's Health, Shahid Beheshti University of Medical Sciences, Tehran, Iran. .,Mofid Children Hospital, Tehran, 1546815514, Iran.
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16
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Monirujjaman M, Renani LB, Isesele P, Dunichand-Hoedl AR, Mazurak VC. Increased Expression of Hepatic Stearoyl-CoA Desaturase (SCD)-1 and Depletion of Eicosapentaenoic Acid (EPA) Content following Cytotoxic Cancer Therapy Are Reversed by Dietary Fish Oil. Int J Mol Sci 2023; 24:ijms24043547. [PMID: 36834959 PMCID: PMC9962117 DOI: 10.3390/ijms24043547] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/30/2022] [Revised: 02/03/2023] [Accepted: 02/07/2023] [Indexed: 02/12/2023] Open
Abstract
Cancer treatment evokes impediments to liver metabolism that culminate in fatty liver. This study determined hepatic fatty acid composition and expression of genes and mediators involved in lipid metabolism following chemotherapy treatment. Female rats bearing the Ward colon tumor were administered Irinotecan (CPT-11) +5-fluorouracil (5-FU) and maintained on a control diet or a diet containing eicosapentaenoic acid (EPA) + docosahexaenoic acid (DHA) (2.3 g/100 g fish oil). Healthy animals provided with a control diet served as a reference group. Livers were collected one week after chemotherapy. Triacylglycerol (TG), phospholipid (PL), ten lipid metabolism genes, leptin, and IL-4 were measured. Chemotherapy increased TG content and reduced EPA content in the liver. Expression of SCD1 was upregulated by chemotherapy, while dietary fish oil downregulated its expression. Dietary fish oil down-regulated expression of the fatty acid synthesis gene FASN, while restoring the long chain fatty acid converting genes FADS2 and ELOVL2, and genes involved in mitochondrial β-oxidation (CPT1α) and lipid transport (MTTP1), to values similar to reference animals. Neither leptin nor IL-4 were affected by chemotherapy or diet. Depletion of EPA is associated with pathways evoking enhanced TG accumulation in the liver. Restoring EPA through diet may pose a dietary strategy to attenuate chemotherapy-associated impediments in liver fatty acid metabolism.
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Hall RL, George ES, Tierney AC, Reddy AJ. Effect of Dietary Intervention, with or without Cointerventions, on Inflammatory Markers in Patients with Nonalcoholic Fatty Liver Disease: A Systematic Review and Meta-Analysis. Adv Nutr 2023; 14:475-499. [PMID: 36796436 DOI: 10.1016/j.advnut.2023.01.001] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/04/2022] [Revised: 12/21/2022] [Accepted: 01/06/2023] [Indexed: 02/04/2023] Open
Abstract
Nonalcoholic fatty liver disease (NAFLD) encompasses a spectrum of disease from simple steatosis to nonalcoholic steatohepatitis, with inflammatory cytokines and adipokines identified as drivers of disease progression. Poor dietary patterns are known to promote an inflammatory milieu, although the effects of specific diets remain largely unknown. This review aimed to gather and summarize new and existing evidence on the effect of dietary intervention on inflammatory markers in patients with NAFLD. The electronic databases MEDLINE, EMBASE, CINAHL, and Cochrane were searched for clinical trials which investigated outcomes of inflammatory cytokines and adipokines. Eligible studies included adults >18 y with NAFLD, which compared a dietary intervention with an alternative diet or control (no intervention) group or were accompanied by supplementation or other lifestyle interventions. Outcomes for inflammatory markers were grouped and pooled for meta-analysis where heterogeneity was allowed. Methodological quality and risk of bias were assessed using the Academy of Nutrition and Dietetics Criteria. Overall, 44 studies with a total of 2579 participants were included. Meta-analyses indicated intervention with an isocaloric diet plus supplement was more effective in reducing C-reactive protein (CRP) [standard mean difference (SMD): 0.44; 95% CI: 0.20, 0.68; P = 0.0003] and tumor necrosis factor-alpha (TNF-α) (SMD: 0.74; 95% CI: 0.02, 1.46; P = 0.03) than an isocaloric diet alone. No significant weighting was shown between a hypocaloric diet with or without supplementation for CRP (SMD: 0.30; 95% CI: -0.84, 1.44; P = 0.60) and TNF-α (SMD: 0.01; 95% CI: -0.43, 0.45; P = 0.97). In conclusion, hypocaloric and energy-restricted diets alone or with supplementation, and isocaloric diets with supplementation were shown to be most effective in improving the inflammatory profile of patients with NAFLD. To better determine the effectiveness of dietary intervention alone on a NAFLD population, further investigations of longer durations, with larger sample sizes are required.
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Affiliation(s)
- Renate L Hall
- School of Allied Health, Human Services and Sport, La Trobe University, Bundoora, Australia
| | - Elena S George
- School of Allied Health, Human Services and Sport, La Trobe University, Bundoora, Australia; Institute for Physical Activity and Nutrition, School of Exercise and Nutrition Sciences, Deakin University, Geelong, Australia
| | - Audrey C Tierney
- School of Allied Health, Human Services and Sport, La Trobe University, Bundoora, Australia; School of Allied Health, Health Implementation Science and Technology Research Cluster, Health Research Institute, University of Limerick, Limerick, Ireland
| | - Anjana J Reddy
- School of Allied Health, Human Services and Sport, La Trobe University, Bundoora, Australia; Exercise and Nutrition Research Program, Mary MacKillop Institute for Health Research, Australian Catholic University, Fitzroy, Australia.
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Chew NW, Muthiah MD, Sanyal AJ. Nonalcoholic fatty liver disease and nonalcoholic steatohepatitis: pathophysiology and implications for cardiovascular disease. CARDIOVASCULAR ENDOCRINOLOGY AND METABOLISM 2023:137-173. [DOI: 10.1016/b978-0-323-99991-5.00003-6] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/03/2025]
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19
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Gutiérrez-Cuevas J, Lucano-Landeros S, López-Cifuentes D, Santos A, Armendariz-Borunda J. Epidemiologic, Genetic, Pathogenic, Metabolic, Epigenetic Aspects Involved in NASH-HCC: Current Therapeutic Strategies. Cancers (Basel) 2022; 15:23. [PMID: 36612019 PMCID: PMC9818030 DOI: 10.3390/cancers15010023] [Citation(s) in RCA: 27] [Impact Index Per Article: 9.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/02/2022] [Revised: 12/12/2022] [Accepted: 12/14/2022] [Indexed: 12/24/2022] Open
Abstract
Hepatocellular carcinoma (HCC) is the most common primary liver cancer and is the sixth most frequent cancer in the world, being the third cause of cancer-related deaths. Nonalcoholic steatohepatitis (NASH) is characterized by fatty infiltration, oxidative stress and necroinflammation of the liver, with or without fibrosis, which can progress to advanced liver fibrosis, cirrhosis and HCC. Obesity, metabolic syndrome, insulin resistance, and diabetes exacerbates the course of NASH, which elevate the risk of HCC. The growing prevalence of obesity are related with increasing incidence of NASH, which may play a growing role in HCC epidemiology worldwide. In addition, HCC initiation and progression is driven by reprogramming of metabolism, which indicates growing appreciation of metabolism in the pathogenesis of this disease. Although no specific preventive pharmacological treatments have recommended for NASH, dietary restriction and exercise are recommended. This review focuses on the molecular connections between HCC and NASH, including genetic and risk factors, highlighting the metabolic reprogramming and aberrant epigenetic alterations in the development of HCC in NASH. Current therapeutic aspects of NASH/HCC are also reviewed.
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Affiliation(s)
- Jorge Gutiérrez-Cuevas
- Department of Molecular Biology and Genomics, Institute for Molecular Biology in Medicine and Gene Therapy, University of Guadalajara, CUCS, Guadalajara 44340, Jalisco, Mexico
| | - Silvia Lucano-Landeros
- Department of Molecular Biology and Genomics, Institute for Molecular Biology in Medicine and Gene Therapy, University of Guadalajara, CUCS, Guadalajara 44340, Jalisco, Mexico
| | - Daniel López-Cifuentes
- Department of Molecular Biology and Genomics, Institute for Molecular Biology in Medicine and Gene Therapy, University of Guadalajara, CUCS, Guadalajara 44340, Jalisco, Mexico
| | - Arturo Santos
- Tecnologico de Monterrey, EMCS, Campus Guadalajara, Zapopan 45201, Jalisco, Mexico
| | - Juan Armendariz-Borunda
- Department of Molecular Biology and Genomics, Institute for Molecular Biology in Medicine and Gene Therapy, University of Guadalajara, CUCS, Guadalajara 44340, Jalisco, Mexico
- Tecnologico de Monterrey, EMCS, Campus Guadalajara, Zapopan 45201, Jalisco, Mexico
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20
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Abdallah M, Brown L, Provenza J, Tariq R, Gowda S, Singal AK. Safety and efficacy of dyslipidemia treatment in NAFLD patients: a meta-analysis of randomized controlled trials. Ann Hepatol 2022; 27:100738. [PMID: 35781090 DOI: 10.1016/j.aohep.2022.100738] [Citation(s) in RCA: 10] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/28/2022] [Revised: 06/24/2022] [Accepted: 06/24/2022] [Indexed: 02/07/2023]
Abstract
INTRODUCTION AND OBJECTIVES Practicing physicians often hesitate to use statins and/or other lipid-lowering therapies in NAFLD due to concern for hepatotoxicity. The aim of this study is to examine the safety of lipid lowering therapies in NAFLD patients. MATERIALS AND METHODS Data from randomized control trials (RCT) among NAFLD patients were pooled to examine the effect of lipid-lowering therapies on liver chemistry, lipid profile, and liver histology. Results are reported as the mean difference of the change (pretreatment-posttreatment) between the treatment and control group. RESULTS A total of 21 placebo-controlled RCT on 1900 patients (304 receiving statins, 520 other lipid-lowering therapies, and 61 combinations) were treated for 26 weeks [Interquartile range (IQR): 17.5-52 weeks]. Pooled data showed an improved lipid profile without any worsening of ALT, AST, total bilirubin, or alkaline phosphatase at the end of the treatment period. NAFLD activity score improved with other lipid-lowering agents but not with statins. There was no change in individual components of NAFLD activity score or fibrosis stage. CONCLUSION This meta-analysis of randomized controlled trials examining statins and/or other lipid-lowering therapies in NAFLD patients showed no evidence of worsening liver chemistry. Studies with longer use of lipid-lowering therapies are suggested to examine the benefit of liver histology among patients with NAFLD.
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Affiliation(s)
- Mohamed Abdallah
- Department of Medicine, University of South Dakota Sanford School of Medicine, Sioux Falls, SD, United States
| | - Landon Brown
- Department of Medicine, University of Alabama at Birmingham, Birmingham, AL, United States
| | - John Provenza
- Department of Medicine, University of Alabama at Birmingham, Birmingham, AL, United States
| | - Raseen Tariq
- Department of Medicine, University of Rochester, NY, United States
| | - Smitha Gowda
- Department of Medicine, University of South Dakota Sanford School of Medicine, Sioux Falls, SD, United States
| | - Ashwani K Singal
- Department of Medicine, University of South Dakota Sanford School of Medicine, Sioux Falls, SD, United States; Division of Transplant Hepatology, Avera Transplant Institute, Sioux Falls, SD, United States.
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21
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Mäkelä TNK, Tuomainen TP, Hantunen S, Virtanen JK. Associations of serum n-3 and n-6 polyunsaturated fatty acids with prevalence and incidence of nonalcoholic fatty liver disease. Am J Clin Nutr 2022; 116:759-770. [PMID: 35648467 PMCID: PMC9437980 DOI: 10.1093/ajcn/nqac150] [Citation(s) in RCA: 28] [Impact Index Per Article: 9.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/01/2021] [Accepted: 05/19/2022] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Nonalcoholic fatty liver disease (NAFLD) is a major cause of liver diseases worldwide, and lifestyle and diet are significant factors in its development. Recent studies have suggested that dietary fat quality is associated with the development of NAFLD. OBJECTIVES Our purpose was to investigate the cross-sectional and longitudinal associations of serum n-3 (ω-3) and n-6 (ω-6) PUFAs with NAFLD among middle-aged and older men and women from eastern Finland. We also investigated the associations of estimated Δ5-desaturase and Δ6-desaturase activities, enzymes involved in PUFA metabolism, with NAFLD. METHODS After exclusions, the cross-sectional analyses included 1533 men examined in 1984-1989 and 674 men and 870 women examined in 1998-2001 in the Kuopio Ischaemic Heart Disease Risk Factor Study. The longitudinal analyses included 520 men examined in 1991-1993 and 301 men and 466 women examined in 2005-2008. Fatty liver index (FLI) was used as a surrogate for NAFLD. Hepatic steatosis was defined as FLI >60. ANCOVA and logistic regression were used for analyses. RESULTS In the longitudinal analyses, participants with higher serum concentrations of total n-6 PUFA and linoleic acid, the major n-6 PUFA, had markedly lower FLI and lower odds for hepatic steatosis (e.g., odds ratios for incident hepatic steatosis in the highest compared with lowest quartiles were ≤0.41), whereas serum γ-linolenic acid concentration was associated with a higher FLI and higher odds for hepatic steatosis. The associations with the other PUFAs were generally weaker and nonsignificant. In the cross-sectional analyses, also the long-chain n-3 PUFAs had inverse associations. In most analyses, high estimated Δ5-desaturase activity was associated with lower risk and high estimated Δ6-desaturase activity with higher risk for NAFLD. CONCLUSIONS In middle-aged and older Finnish adults, higher serum concentrations of total n-6 PUFAs and linoleic acid were associated with lower odds for future NAFLD.
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Affiliation(s)
- Tiia N K Mäkelä
- Institute of Clinical Medicine, University of Eastern Finland, Finland
| | - Tomi-Pekka Tuomainen
- Institute of Public Health and Clinical Nutrition, University of Eastern Finland, Kuopio, Finland
| | - Sari Hantunen
- Institute of Public Health and Clinical Nutrition, University of Eastern Finland, Kuopio, Finland
| | - Jyrki K Virtanen
- Institute of Public Health and Clinical Nutrition, University of Eastern Finland, Kuopio, Finland
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22
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Ding X, Xu Y, Nie P, Zhong L, Feng L, Guan Q, Song L. Changes in the serum metabolomic profiles of subjects with NAFLD in response to n-3 PUFAs and phytosterol ester: a double-blind randomized controlled trial. Food Funct 2022; 13:5189-5201. [PMID: 35438091 DOI: 10.1039/d1fo03921k] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
Nonalcoholic fatty liver disease (NAFLD) has become the most common cause of chronic liver disease and threatens human health worldwide. As shown in our previous study, co-supplementation with phytosterol ester (PSE) (3.3 g day-1) and n-3 polyunsaturated fatty acids (PUFAs) (450 mg eicosapentaenoic acid (EPA) + 1500 mg docosahexaenoic acid (DHA) per day) was more effective at ameliorating hepatic steatosis than treatment with PSE or n-3 PUFAs alone. In the present study, we further investigated the changes in the serum metabolic profiles of subjects with NAFLD in response to n-3 PUFAs and PSE. Thirty-one differentially altered serum metabolites were annotated using the nontargeted ultra-performance liquid chromatography-quadrupole/time-of-flight mass spectrometry (UPLC-Q-TOF-MSE) analysis technique. Multivariable statistical and clustering analyses showed that co-supplementation of n-3 PUFAs and PSE was more effective at improving metabolic disorders in patients with NAFLD than treatment with n-3 PUFAs or PSE alone. The regulated metabolic pathways included metabolism of retinol, linoleic acid, arachidonic acid, glycerophospholipid, sphingolipid, and steroid hormone biosynthesis. Overall, the co-supplementation of n-3 PUFAs and PSE significantly increased the serum levels of PUFA-containing phosphatidylcholine (PC), lysophosphatidylcholine (LysoPC), perillyl alcohol and retinyl ester in patients with NAFLD after 12 weeks of intervention, and the levels of PC (14:0/20:5, 15:0/20:5), LysoPC (20:5, 22:6) and retinyl ester correlated negatively with the degree of hepatic steatosis. The regulatory effect of co-supplementation of n-3 PUFAs and PSE on metabolomic profiles may explain their potential role in alleviating hepatic steatosis in patients with NAFLD.
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Affiliation(s)
- Xinwen Ding
- School of Agriculture and Biology, Shanghai Jiao Tong University, Shanghai 200240, China.
| | - Yinfei Xu
- The First People's Hospital of Ningyang County, Tai'an City 270018, Shandong Province, People's Republic of China
| | - Pan Nie
- School of Agriculture and Biology, Shanghai Jiao Tong University, Shanghai 200240, China.
| | - Lingyue Zhong
- School of Agriculture and Biology, Shanghai Jiao Tong University, Shanghai 200240, China.
| | - Lei Feng
- Instrumental Analysis Center, Shanghai Jiao Tong University, Shanghai 200240, People's Republic of China
| | - Qi Guan
- School of Agriculture and Biology, Shanghai Jiao Tong University, Shanghai 200240, China.
| | - Lihua Song
- School of Agriculture and Biology, Shanghai Jiao Tong University, Shanghai 200240, China.
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23
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Comprehensive Review and Updates on Holistic Approach Towards Non-Alcoholic Fatty Liver Disease Management with Cardiovascular Disease. Curr Atheroscler Rep 2022; 24:515-532. [PMID: 35507280 DOI: 10.1007/s11883-022-01027-5] [Citation(s) in RCA: 25] [Impact Index Per Article: 8.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 04/01/2022] [Indexed: 02/06/2023]
Abstract
PURPOSE OF REVIEW The global prevalence of non-alcoholic fatty liver disease (NAFLD) presents an unmet need in treating these, often asymptomatic, individuals. In this review, we summarised NAFLD management and described recent developments in non-alcoholic steatohepatitis (NASH) therapeutics that can shape the future of NAFLD. RECENT FINDINGS A multi-disciplinary effort in promoting sustainable lifestyle measures is paramount, with the goal of either limiting energy surplus alone or in combination with targeting downstream pathways of inflammation and fibrosis. Several antidiabetic medications like PPAR-γ agonist and glucagon-like peptide receptor agonists have beneficial effects on the metabolic profile as well as NASH histology. Vitamin E has shown promise in specific groups of patients with the haptoglobin2 allele protein. Newer drugs have demonstrated promising results in NASH resolution and fibrosis improvement such as obeticholic acid, resmetirom, aramchol, efruxifermin, aldafermin and lanifibranor. Apart from discussing the results of late stage clinical trials and the possible challenges in managing these patients with limited approved therapies, we also discussed the specific management of comorbidities (diabetes, hypertension, hyperlipidaemia, cardiovascular diseases) in NAFLD patients. Treatment strategy needs to target improvements in liver-related outcomes and cardiometabolic profile.
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24
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Tzanaki I, Agouridis AP, Kostapanos MS. Is there a role of lipid-lowering therapies in the management of fatty liver disease? World J Hepatol 2022; 14:119-139. [PMID: 35126843 PMCID: PMC8790403 DOI: 10.4254/wjh.v14.i1.119] [Citation(s) in RCA: 15] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/17/2021] [Revised: 08/30/2021] [Accepted: 12/07/2021] [Indexed: 02/06/2023] Open
Abstract
Atherogenic dyslipidemia is characterized by increased triglyceride-rich lipoproteins and low high-density lipoprotein cholesterol concentrations. It is highly prevalent in non-alcoholic fatty liver disease (NAFLD) and contributes to the increased cardiovascular risk associated with this condition. Alongside insulin resistance it plays an important pathogenetic role in NAFLD/non-alcoholic steatohepatitis (NASH) development and progression. It has been shown that cholesterol-lowering reduces cardiovascular risk more in NAFLD vs non-NAFLD high-risk individuals. This evidence highlights the importance of effective lipid modulation in NAFLD. In this narrative review the effects of the most commonly used lipid-lowering therapies on liver outcomes alongside their therapeutic implications in NAFLD/NASH are critically discussed. Preclinical and clinical evidence suggests that statins reduce hepatic steatosis, inflammation and fibrosis in patients with NAFLD/NASH. Most data are derived from observational and small prospective clinical studies using changes in liver enzyme activities, steatosis/fibrosis scores, and imaging evidence of steatosis as surrogates. Also, relevant histologic benefits were noted in small biopsy studies. Atorvastatin and rosuvastatin showed greater benefits, whereas data for other statins are scarce and sometimes conflicting. Similar studies to those of statins showed efficacy of ezetimibe against hepatic steatosis. However, no significant anti-inflammatory and anti-fibrotic actions of ezetimibe have been shown. Preclinical studies showed that fibrates through peroxisome proliferator-activated receptor (PPAR)α activation may have a role in NAFLD prevention and management. Nevertheless, no relevant benefits have been noted in human studies. Species-related differences in PPARα expression and its activation responsiveness may help explain this discrepancy. Omega-3 fatty acids reduced hepatic steatosis in numerous heterogeneous studies, but their benefits on hepatic inflammation and fibrosis have not been established. Promising preliminary data for the highly purified eicosapentaenoic acid require further confirmation. Observational studies suggest that proprotein convertase subtilisin/kexin9 inhibitors may also have a role in the management of NAFLD, though this needs to be established by future prospective studies.
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Affiliation(s)
- Ismini Tzanaki
- School of Medicine, European University Cyprus, Nicosia, Cyprus, Nicosia 2404, Cyprus
| | - Aris P Agouridis
- School of Medicine, European University Cyprus, Nicosia 2404, Cyprus
| | - Michael S Kostapanos
- General Medicine, Addenbrooke's Hospital, Cambridge University Hospitals, Cambridge CB20QQ, United Kingdom.
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25
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Son HK, Kim BH, Lee J, Park S, Oh CB, Jung S, Lee JK, Ha JH. Partial Replacement of Dietary Fat with Krill Oil or Coconut Oil Alleviates Dyslipidemia by Partly Modulating Lipid Metabolism in Lipopolysaccharide-Injected Rats on a High-Fat Diet. INTERNATIONAL JOURNAL OF ENVIRONMENTAL RESEARCH AND PUBLIC HEALTH 2022; 19:843. [PMID: 35055664 PMCID: PMC8775371 DOI: 10.3390/ijerph19020843] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 11/30/2021] [Revised: 01/06/2022] [Accepted: 01/08/2022] [Indexed: 02/04/2023]
Abstract
This study investigated the effects of partial replacement of dietary fat with krill oil (KO) or coconut oil (CO) on dyslipidemia and lipid metabolism in rats fed with a high-fat diet (HFD). Sprague Dawley rats were divided into three groups as follows: HFD, HFD + KO, and HFD + CO. The rats were fed each diet for 10 weeks and then intraperitoneally injected with phosphate-buffered saline (PBS) or lipopolysaccharide (LPS) (1 mg/kg). The KO- and CO-fed rats exhibited lower levels of serum lipids and aspartate aminotransferases than those of the HFD-fed rats. Rats fed with HFD + KO displayed significantly lower hepatic histological scores and hepatic triglyceride (TG) content than rats fed with HFD. The KO supplementation also downregulated the adipogenic gene expression in the liver. When treated with LPS, the HFD + KO and HFD + CO groups reduced the adipocyte size in the epididymal white adipose tissues (EAT) relative to the HFD group. These results suggest that KO and CO could improve lipid metabolism dysfunction.
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Affiliation(s)
- Hee-Kyoung Son
- Research Center for Industrialization of Natural Neutralization, Dankook University, Cheonan 31116, Korea; (H.-K.S.); (J.L.); (S.P.); (S.J.)
| | - Bok-Hee Kim
- Department of Food and Nutrition, Chosun University, Gwangju 61452, Korea;
| | - Jisu Lee
- Research Center for Industrialization of Natural Neutralization, Dankook University, Cheonan 31116, Korea; (H.-K.S.); (J.L.); (S.P.); (S.J.)
- Department of Food Science and Nutrition, Dankook University, Cheonan 31116, Korea
| | - Seohyun Park
- Research Center for Industrialization of Natural Neutralization, Dankook University, Cheonan 31116, Korea; (H.-K.S.); (J.L.); (S.P.); (S.J.)
- Department of Food Science and Nutrition, Dankook University, Cheonan 31116, Korea
| | - Chung-Bae Oh
- Office of Technical Liaison, Industry Support Team, Gyeongnam Branch Institute, Korea Institute of Toxicology, Jinju 52834, Korea;
| | - Sunyoon Jung
- Research Center for Industrialization of Natural Neutralization, Dankook University, Cheonan 31116, Korea; (H.-K.S.); (J.L.); (S.P.); (S.J.)
- Department of Food Science and Nutrition, Dankook University, Cheonan 31116, Korea
| | - Jennifer K. Lee
- Food Science and Human Nutrition Department, University of Florida, Gainesville, FL 32611, USA
| | - Jung-Heun Ha
- Research Center for Industrialization of Natural Neutralization, Dankook University, Cheonan 31116, Korea; (H.-K.S.); (J.L.); (S.P.); (S.J.)
- Department of Food Science and Nutrition, Dankook University, Cheonan 31116, Korea
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26
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Satiya J, Snyder HS, Singh SP, Satapathy SK. Narrative review of current and emerging pharmacological therapies for nonalcoholic steatohepatitis. Transl Gastroenterol Hepatol 2021; 6:60. [PMID: 34805582 PMCID: PMC8573363 DOI: 10.21037/tgh-20-247] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/14/2020] [Accepted: 09/25/2020] [Indexed: 12/28/2022] Open
Abstract
Nonalcoholic steatohepatitis (NASH) is the most common cause of chronic liver disease today, and it has now emerged as the leading etiology of end-stage liver disease requiring liver transplantation. It is a progressive form of non-alcoholic fatty liver disease which can not only progress to cirrhosis of liver and hepatocellular carcinoma (HCC), but is associated with increased cardiovascular risks too. Despite all the advances in the understanding of the risk factors and the pathogenetic pathways involved in the pathogenesis and progression of NASH, an effective therapy for NASH has not been developed yet. Although lifestyle modifications including dietary modifications and physical activity remain the mainstay of therapy, there is an unmet need to develop a drug or a combination of drugs which can not only reduce the fatty infiltration of the liver, but also arrest the development and progression of fibrosis and advancement to cirrhosis of liver and HCC. The pharmacologic therapies which are being developed target the various components believed to be involved in the pathogenesis of nonalcoholic fatty liver disease (NAFLD)/NASH which includes insulin resistance, lipid metabolism oxidative stress, lipid peroxidation, inflammatory and cell death pathways, and fibrosis. In this review, we summarize the current state of knowledge on pharmacotherapy of NASH, and also highlight the recent developments in the field, for optimizing the management and treatment of NASH.
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Affiliation(s)
- Jinendra Satiya
- Division of Gastroenterology and Hepatology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA
| | | | - Shivaram Prasad Singh
- Department of Gastroenterology, S.C.B. Medical College, Cuttack, India
- Kalinga Gastroenterology Foundation, Beam Diagnostics Centre, Cuttack, India
| | - Sanjaya K. Satapathy
- Division of Hepatology, Sandra Atlas Bass Center for Liver Diseases and Transplantation, Northwell Health, Manhasset, NY, USA
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27
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Herrera Vielma F, Valenzuela R, Videla LA, Zúñiga-Hernández J. N-3 Polyunsaturated Fatty Acids and Their Lipid Mediators as A Potential Immune-Nutritional Intervention: A Molecular and Clinical View in Hepatic Disease and Other Non-Communicable Illnesses. Nutrients 2021; 13:3384. [PMID: 34684386 PMCID: PMC8539469 DOI: 10.3390/nu13103384] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/14/2021] [Revised: 09/11/2021] [Accepted: 09/14/2021] [Indexed: 02/06/2023] Open
Abstract
In recent years, the beneficial effect of n-3 polyunsaturated fatty acids (n-3 PUFAs) intake on human health has been widely accepted in the field of immunonutrition. Today, we find a diversity of supplements based on n-3 PUFAs and/or minerals, vitamins and other substances. The main objective of this review is to discuss the importance of n-3 PUFAs and their derivatives on immunity and inflammatory status related to liver disease and other non-communicable illnesses. Based on the burden of liver diseases in 2019, more than two million people die from liver pathologies per year worldwide, because it is the organ most exposed to agents such as viruses, toxins and medications. Consequently, research conducted on n-3 PUFAs for liver disease has been gaining prominence with encouraging results, given that these fatty acids have anti-inflammatory and cytoprotective effects. In addition, it has been described that n-3 PUFAs are converted into a novel species of lipid intermediaries, specialized pro-resolving mediators (SPMs). At specific levels, SPMs improve the termination of inflammation as well as the repairing and regeneration of tissues, but they are deregulated in liver disease. Since evidence is still insufficient to carry out pharmacological trials to benefit the resolution of acute inflammation in non-communicable diseases, there remains a call for continuing preclinical and clinical research to better understand SPM actions and outcomes.
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Affiliation(s)
- Francisca Herrera Vielma
- Department of Biomedical Basic Sciences, School of Health Sciences, University of Talca, Talca 3460000, Chile;
| | - Rodrigo Valenzuela
- Department of Nutrition, Faculty of Medicine, University of Chile, Santiago 8380000, Chile;
| | - Luis A. Videla
- Molecular and Clinical Pharmacology Program, Institute of Biomedical Science, Faculty of Medicine, University of Chile, Santiago 8380000, Chile;
| | - Jessica Zúñiga-Hernández
- Department of Biomedical Basic Sciences, School of Health Sciences, University of Talca, Talca 3460000, Chile;
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Komolafe O, Buzzetti E, Linden A, Best LM, Madden AM, Roberts D, Chase TJ, Fritche D, Freeman SC, Cooper NJ, Sutton AJ, Milne EJ, Wright K, Pavlov CS, Davidson BR, Tsochatzis E, Gurusamy KS. Nutritional supplementation for nonalcohol-related fatty liver disease: a network meta-analysis. Cochrane Database Syst Rev 2021; 7:CD013157. [PMID: 34280304 PMCID: PMC8406904 DOI: 10.1002/14651858.cd013157.pub2] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/30/2023]
Abstract
BACKGROUND The prevalence of non-alcohol-related fatty liver disease (NAFLD) varies between 19% and 33% in different populations. NAFLD decreases life expectancy and increases risks of liver cirrhosis, hepatocellular carcinoma, and the requirement for liver transplantation. Uncertainty surrounds relative benefits and harms of various nutritional supplements in NAFLD. Currently no nutritional supplement is recommended for people with NAFLD. OBJECTIVES • To assess the benefits and harms of different nutritional supplements for treatment of NAFLD through a network meta-analysis • To generate rankings of different nutritional supplements according to their safety and efficacy SEARCH METHODS: We searched the Cochrane Central Register of Controlled Trials, MEDLINE, Embase, Science Citation Index Expanded, Conference Proceedings Citation Index-Science, the World Health Organization International Clinical Trials Registry Platform, and trials registers until February 2021 to identify randomised clinical trials in people with NAFLD. SELECTION CRITERIA We included only randomised clinical trials (irrespective of language, blinding, or status) for people with NAFLD, irrespective of method of diagnosis, age and diabetic status of participants, or presence of non-alcoholic steatohepatitis (NASH). We excluded randomised clinical trials in which participants had previously undergone liver transplantation. DATA COLLECTION AND ANALYSIS We performed a network meta-analysis with OpenBUGS using Bayesian methods whenever possible and calculated differences in treatments using hazard ratios (HRs), odds ratios (ORs), and rate ratios with 95% credible intervals (CrIs) based on an available-case analysis, according to National Institute of Health and Care Excellence Decision Support Unit guidance. MAIN RESULTS We included in the review a total of 202 randomised clinical trials (14,200 participants). Nineteen trials were at low risk of bias. A total of 32 different interventions were compared in these trials. A total of 115 trials (7732 participants) were included in one or more comparisons. The remaining trials did not report any of the outcomes of interest for this review. Follow-up ranged from 1 month to 28 months. The follow-up period in trials that reported clinical outcomes was 2 months to 28 months. During this follow-up period, clinical events related to NAFLD such as mortality, liver cirrhosis, liver decompensation, liver transplantation, hepatocellular carcinoma, and liver-related mortality were sparse. We did not calculate effect estimates for mortality because of sparse data (zero events for at least one of the groups in the trial). None of the trials reported that they measured overall health-related quality of life using a validated scale. The evidence is very uncertain about effects of interventions on serious adverse events (number of people or number of events). We are very uncertain about effects on adverse events of most of the supplements that we investigated, as the evidence is of very low certainty. However, people taking PUFA (polyunsaturated fatty acid) may be more likely to experience an adverse event than those not receiving an active intervention (network meta-analysis results: OR 4.44, 95% CrI 2.40 to 8.48; low-certainty evidence; 4 trials, 203 participants; direct evidence: OR 4.43, 95% CrI 2.43 to 8.42). People who take other supplements (a category that includes nutritional supplements other than vitamins, fatty acids, phospholipids, and antioxidants) had higher numbers of adverse events than those not receiving an active intervention (network meta-analysis: rate ratio 1.73, 95% CrI 1.26 to 2.41; 6 trials, 291 participants; direct evidence: rate ratio 1.72, 95% CrI 1.25 to 2.40; low-certainty evidence). Data were sparse (zero events in all groups in the trial) for liver transplantation, liver decompensation, and hepatocellular carcinoma. So, we did not perform formal analysis for these outcomes. The evidence is very uncertain about effects of other antioxidants (antioxidants other than vitamins) compared to no active intervention on liver cirrhosis (HR 1.68, 95% CrI 0.23 to 15.10; 1 trial, 99 participants; very low-certainty evidence). The evidence is very uncertain about effects of interventions in any of the remaining comparisons, or data were sparse (with zero events in at least one of the groups), precluding formal calculations of effect estimates. Data were probably because of the very short follow-up period (2 months to 28 months). It takes follow-up of 8 to 28 years to detect differences in mortality between people with NAFLD and the general population. Therefore, it is unlikely that differences in clinical outcomes are noted in trials providing less than 5 to 10 years of follow-up. AUTHORS' CONCLUSIONS The evidence indicates considerable uncertainty about effects of nutritional supplementation compared to no additional intervention on all clinical outcomes for people with non-alcohol-related fatty liver disease. Accordingly, high-quality randomised comparative clinical trials with adequate follow-up are needed. We propose registry-based randomised clinical trials or cohort multiple randomised clinical trials (study design in which multiple interventions are trialed within large longitudinal cohorts of patients to gain efficiencies and align trials more closely to standard clinical practice) comparing interventions such as vitamin E, prebiotics/probiotics/synbiotics, PUFAs, and no nutritional supplementation. The reason for the choice of interventions is the impact of these interventions on indirect outcomes, which may translate to clinical benefit. Outcomes in such trials should be mortality, health-related quality of life, decompensated liver cirrhosis, liver transplantation, and resource utilisation measures including costs of intervention and decreased healthcare utilisation after minimum follow-up of 8 years (to find meaningful differences in clinically important outcomes).
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Affiliation(s)
| | - Elena Buzzetti
- Sheila Sherlock Liver Centre, Royal Free Hospital and the UCL Institute of Liver and Digestive Health, London, UK
| | - Audrey Linden
- Division of Surgery and Interventional Science, University College London, London, UK
| | - Lawrence Mj Best
- Division of Surgery and Interventional Science, University College London, London, UK
| | - Angela M Madden
- School of Life and Medical Sciences, University of Hertfordshire, Hatfield, UK
| | - Danielle Roberts
- Division of Surgery and Interventional Science, University College London, London, UK
| | - Thomas Jg Chase
- Department of General Surgery, Homerton University Hospital NHS Foundation Trust, London, UK
| | | | - Suzanne C Freeman
- Department of Health Sciences, University of Leicester, Leicester, UK
| | - Nicola J Cooper
- Department of Health Sciences, University of Leicester, Leicester, UK
| | - Alex J Sutton
- Department of Health Sciences, University of Leicester, Leicester, UK
| | | | - Kathy Wright
- Cochrane Hepato-Biliary Group, Copenhagen Trial Unit, Centre for Clinical Intervention Research, The Capital Region of Denmark, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark
| | - Chavdar S Pavlov
- Department of Therapy, I.M. Sechenov First Moscow State Medical University, Moscow, Russian Federation
| | - Brian R Davidson
- Division of Surgery and Interventional Science, University College London, London, UK
| | - Emmanuel Tsochatzis
- Sheila Sherlock Liver Centre, Royal Free Hospital and the UCL Institute of Liver and Digestive Health, London, UK
| | - Kurinchi Selvan Gurusamy
- Division of Surgery and Interventional Science, University College London, London, UK
- Department of Therapy, I.M. Sechenov First Moscow State Medical University, Moscow, Russian Federation
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Sangouni AA, Orang Z, Mozaffari-Khosravi H. Effect of omega-3 supplementation on fatty liver and visceral adiposity indices in diabetic patients with non-alcoholic fatty liver disease: A randomized controlled trial. Clin Nutr ESPEN 2021; 44:130-135. [PMID: 34330456 DOI: 10.1016/j.clnesp.2021.06.015] [Citation(s) in RCA: 20] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/27/2021] [Revised: 06/05/2021] [Accepted: 06/18/2021] [Indexed: 12/18/2022]
Abstract
BACKGROUND AND AIMS Non-alcoholic fatty liver disease (NAFLD) as the most common chronic liver disease is closely linked to type 2 diabetes mellitus (T2DM). Omega-3 supplementation has been proposed as a strategy to manage T2DM and NAFLD. The present study aimed to investigate the effect of omega-3 supplementation on fatty liver index, lipid accumulation product and visceral adiposity index in diabetic patients with NAFLD. METHODS In this 12-week double-blind, randomized controlled clinical trial, sixty diabetic patients with NAFLD were randomly assigned into the omega-3 and placebo groups for 12 weeks. The omega-3 group received 2000 mg/d omega-3 as capsule. RESULTS Fifty-six participants completed the study. No significant difference was found between the two groups in the terms of fatty liver index, lipid accumulation product and visceral adiposity index at the baseline. Omega-3 supplementation compared with the placebo led to a significant improvement in fatty liver index (-3.6 ± 12.1 vs. 0.9 ± 8.9; P = 0.04), lipid accumulation product (-14.2 ± 27.9 vs. 8.0 ± 26.3; P = 0.002) and visceral adiposity index (-0.5 ± 0.9 vs. 0.0 ± 0.8; P = 0.01). CONCLUSION Omega-3 supplementation for 12 weeks improves fatty liver index, lipid accumulation product and visceral adiposity index. The study protocol was registered under Iranian Registry of Clinical Trials identifier number IRCT2016102530489N1.
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Affiliation(s)
- Abbas Ali Sangouni
- Department of Nutrition, School of Public Health, Shahid Sadoughi University of Medical Sciences, Yazd, Iran; Nutrition and Food Security Research Center, Shahid Sadoughi University of Medical Sciences, Yazd, Iran
| | - Zahra Orang
- Department of Nutrition, School of Public Health, Shahid Sadoughi University of Medical Sciences, Yazd, Iran; Nutrition and Food Security Research Center, Shahid Sadoughi University of Medical Sciences, Yazd, Iran
| | - Hassan Mozaffari-Khosravi
- Department of Nutrition, School of Public Health, Shahid Sadoughi University of Medical Sciences, Yazd, Iran; Nutrition and Food Security Research Center, Shahid Sadoughi University of Medical Sciences, Yazd, Iran.
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Luo H, Zhao M, Feng X, Gao X, Hong M, Liu M, Li Y, Liu W, Liu Y, Yu C, Cao Y, Yang X, Fang Z, Zhang P. Decreased plasma n6 : n3 polyunsaturated fatty acids ratio interacting with high C-peptide promotes non-alcoholic fatty liver disease in type 2 diabetes patients. J Diabetes Investig 2021; 12:1263-1271. [PMID: 33244871 PMCID: PMC8264392 DOI: 10.1111/jdi.13469] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/21/2020] [Revised: 10/28/2020] [Accepted: 11/12/2020] [Indexed: 12/13/2022] Open
Abstract
AIMS/INTRODUCTION To explore relationships between polyunsaturated fatty acids (PUFA) and non-alcoholic fatty liver disease (NAFLD) in patients with type 2 diabetes, and whether insulin action has an interactive effect with PUFA on NAFLD progression. MATERIALS AND METHODS We extracted clinical and omics data of 482 type 2 diabetes patients from a tertiary hospital consecutively from April 2018 to April 2019. NAFLD was estimated by ultrasound at admission. Plasma fasting n3 and n6 fatty acids were quantified by liquid chromatography-tandem mass spectrometry analysis. Restricted cubic spline nested in binary logistic regression was used to select the cut-off point, and estimate odds ratios and 95% confidence intervals. Additive interactions of the n6 : n3 ratio with insulin action for NAFLD were estimated using relative excess risk due to interaction, attributable proportion due to interaction and synergy index. Relative excess risk due to interaction >0, attributable proportion due to interaction >0 or synergy index >1 indicates biological interaction. Spearman correlation analysis was used to obtain partial correlation coefficients between PUFA and hallmarks of NAFLD. RESULTS Of 482 patients, 313 were with and 169 were without NAFLD. N3 ≥800 and n6 PUFA ≥8,100 μmol/L were independently associated with increased NAFLD risk; n6 : n3 ratio ≤10 was associated with NAFLD (odds ratio 1.80, 95% confidence interval 1.20-2.71), and the effect size was amplified by high C-peptide (odds ratio 8.89, 95% confidence interval 4.48-17.7) with significant interaction. The additive interaction of the n6 : n3 ratio and fasting insulin was not significant. CONCLUSION Decreased n6 : n3 ratio was associated with increased NAFLD risk in type 2 diabetes patients, and the effect was only significant and amplified when there was the co-presence of high C-peptide.
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Affiliation(s)
- Hui‐Huan Luo
- Department of EndocrinologyThe Second Affiliated Hospital of Dalian Medical UniversityDalianChina
- Department of Toxicology and Sanitary ChemistrySchool of Public HealthTianjin Medical UniversityTianjinChina
| | - Meng‐Di Zhao
- Department of EndocrinologyThe Second Affiliated Hospital of Dalian Medical UniversityDalianChina
| | - Xiao‐Fei Feng
- Department of Toxicology and Sanitary ChemistrySchool of Public HealthTianjin Medical UniversityTianjinChina
| | - Xiao‐Qian Gao
- Department of Toxicology and Sanitary ChemistrySchool of Public HealthTianjin Medical UniversityTianjinChina
| | - Mo Hong
- RSKT Biopharma IncDalianLiaoningChina
| | | | - Yan‐Ping Li
- Department of EndocrinologyThe Second Affiliated Hospital of Dalian Medical UniversityDalianChina
| | - Wan‐Qiu Liu
- Department of EndocrinologyThe Second Affiliated Hospital of Dalian Medical UniversityDalianChina
| | - Yu‐Mo Liu
- Department of EndocrinologyThe Second Affiliated Hospital of Dalian Medical UniversityDalianChina
| | - Cheng‐Cheng Yu
- Department of EndocrinologyThe Second Affiliated Hospital of Dalian Medical UniversityDalianChina
| | - Yun‐Feng Cao
- RSKT Biopharma IncDalianLiaoningChina
- Dalian Institute of Chemical PhysicsChinese Academy of SciencesBeijingChina
| | - Xi‐Lin Yang
- Department of Epidemiology and BiostatisticsSchool of Public HealthTianjin Medical UniversityTianjinChina
| | - Zhong‐Ze Fang
- Department of Toxicology and Sanitary ChemistrySchool of Public HealthTianjin Medical UniversityTianjinChina
| | - Ping Zhang
- Department of EndocrinologyThe Second Affiliated Hospital of Dalian Medical UniversityDalianChina
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Mega A, Marzi L, Kob M, Piccin A, Floreani A. Food and Nutrition in the Pathogenesis of Liver Damage. Nutrients 2021; 13:nu13041326. [PMID: 33923822 PMCID: PMC8073814 DOI: 10.3390/nu13041326] [Citation(s) in RCA: 15] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/20/2021] [Revised: 04/10/2021] [Accepted: 04/12/2021] [Indexed: 11/19/2022] Open
Abstract
The liver is an important organ and plays a key role in the regulation of metabolism and in the secretion, storage, and detoxification of endogenous and exogenous substances. The impact of food and nutrition on the pathophysiological mechanisms of liver injury represents a great controversy. Several environmental factors including food and micronutrients are involved in the pathogenesis of liver damage. Conversely, some xenobiotics and micronutrients have been recognized to have a protective effect in several liver diseases. This paper offers an overview of the current knowledge on the role of xenobiotics and micronutrients in liver damage.
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Affiliation(s)
- Andrea Mega
- Gastroenterology Department, Bolzano Regional Hospital, 39100 Bolzano, Italy;
- Correspondence:
| | - Luca Marzi
- Gastroenterology Department, Bolzano Regional Hospital, 39100 Bolzano, Italy;
| | - Michael Kob
- Dietetics and Clinical Nutrition Unit, Bolzano Regional Hospital, 39100 Bolzano, Italy;
| | - Andrea Piccin
- Northern Ireland Blood Transfusion Service, Belfast BT9 7TS, UK;
- Department of Internal Medicine V, Medical University of Innsbruck, A-6020 Innsbruck, Austria
- Department of Industrial Engineering, University of Trento, 38100 Trento, Italy
| | - Annarosa Floreani
- Scientific Institute for Research, Hospitalization and Healthcare, 37024 Negrar-Verona, Italy;
- Department Surgery, Oncology and Gastroenterology, University of Padova, 35128 Padova, Italy
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Kim A, Krishnan A, Hamilton JP, Woreta TA. The Impact of Dietary Patterns and Nutrition in Nonalcoholic Fatty Liver Disease. Gastroenterol Clin North Am 2021; 50:217-241. [PMID: 33518166 DOI: 10.1016/j.gtc.2020.10.013] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
Nonalcoholic fatty liver disease (NAFLD) has become one of the most common causes of chronic liver disease worldwide. The prevalence of NAFLD has grown proportionally with the rise in obesity, sedentary lifestyle, unhealthy dietary patterns, and metabolic syndrome. Currently, in the absence of approved pharmacologic treatment, the keystone of treatment is lifestyle modification focused on achieving a weight loss of 7%-10%, cardiovascular exercise, and improving insulin sensitivity. The primary aim of this review is to outline the effect of different dietetic approaches against NAFLD and highlight the important micronutrient components in the management of NAFLD.
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Affiliation(s)
- Ahyoung Kim
- Division of Gastroenterology and Hepatology, Johns Hopkins University School of Medicine, Baltimore, MD, USA
| | - Arunkumar Krishnan
- Division of Gastroenterology and Hepatology, Johns Hopkins University School of Medicine, Baltimore, MD, USA
| | - James P Hamilton
- Division of Gastroenterology and Hepatology, Johns Hopkins University School of Medicine, Baltimore, MD, USA
| | - Tinsay A Woreta
- Division of Gastroenterology and Hepatology, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
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Abstract
PURPOSE OF REVIEW To discuss the effect of fish oils on dyslipidemias and associated disorders. RECENT FINDINGS The most important lipid effect of fish oils is reducing plasma triglycerides and the main potential protection against cardiovascular events is very probably mediated also through other mechanisms including anti-inflammatory ones. The best results are available for omega-3 fatty acids, namely, eicosapentaenoic acid. Less evidence is available for the impact of ω-3 fatty acids on liver steatosis/steatohepatitis and acute pancreatitis. In addition, particular fish oils have variable content of saturated and unsaturated fatty acids with different anti- or pro-oxidative potential, and the suboptimal ratio of these compounds could attenuate or abolish their beneficial properties. Fish products with optimal proportion of fatty acids, particularly high content of eicosapentaenoic acid, could be recommended to patients with dyslipidemias, especially to those at high risk for cardiovascular disease; less evidence is available for liver disease and acute pancreatitis.
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Reddy AJ, George ES, Roberts SK, Tierney AC. Effect of dietary intervention, with or without co-interventions, on inflammatory markers in patients with nonalcoholic fatty liver disease: a systematic literature review. Nutr Rev 2021; 77:765-786. [PMID: 31361003 DOI: 10.1093/nutrit/nuz029] [Citation(s) in RCA: 16] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
CONTEXT Nonalcoholic fatty liver disease (NAFLD) represents a spectrum of liver disorders, ranging from simple steatosis to nonalcoholic steatohepatitis (NASH), with inflammation acting as a key driver in its pathogenesis and progression. Diet has the potential to mediate the release of inflammatory markers; however, little is known about the effects of various diets. OBJECTIVE This systematic review aimed to evaluate the effect of dietary interventions on cytokines and adipokines in patients with NAFLD. DATA SOURCES The electronic databases MEDLINE, EMBASE, CINAHL, and Cochrane Library were searched for clinical trials investigating dietary interventions, with or without supplementation, on cytokines and adipokines in NAFLD patients. DATA EXTRACTION Basic characteristics of populations, dietary intervention protocol, cytokines, and adipokines were extracted for each study. Quality of evidence was assessed using the American Dietetic Association criteria. DATA ANALYSIS Nineteen studies with a total of 874 participants were included. The most frequently reported inflammatory outcomes were C-reactive protein (CRP), tumor necrosis factor alpha (TNF-α), interleukin 6 (IL-6), adiponectin, and leptin. Hypocaloric, isocaloric, or low-fat diets significantly (P < 0.05) lowered levels of CRP, TNF-α, and adiponectin. The addition of nutraceutical or pharmacological supplementation to dietary interventions appeared to elicit additional benefits for all of the most frequently reported inflammatory markers. CONCLUSIONS Hypo- or isocaloric diets alone, or with co-interventions that included a nutraceutical or pharmacological supplementation, appear to improve the inflammatory profile in patients with NAFLD. Thus, anti-inflammatory diets may have the potential to improve underlying chronic inflammation that underpins the pathophysiological mechanisms of NAFLD. In the absence of any known liver-sensitive markers, the use of cytokines and adipokines as a surrogate marker of liver disease should be further investigated in well-controlled trials.
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Affiliation(s)
- Anjana J Reddy
- Department of Rehabilitation, Nutrition and Sport, La Trobe University, Bundoora, Victoria, Australia
| | - Elena S George
- Department of Rehabilitation, Nutrition and Sport, La Trobe University, Bundoora, Victoria, Australia
- Institute for Physical Activity and Nutrition, School of Exercise and Nutrition Sciences, Deakin University, Geelong, Victoria, Australia
- Department of Nutrition, Alfred Health, Prahran, Victoria, Australia
| | - Stuart K Roberts
- Department of Gastroenterology, Alfred Health, Prahran, Victoria, Australia
| | - Audrey C Tierney
- Department of Rehabilitation, Nutrition and Sport, La Trobe University, Bundoora, Victoria, Australia
- Department of Nutrition, Alfred Health, Prahran, Victoria, Australia
- School of Allied Health, University of Limerick, Limerick, Ireland
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AlFaris NA, Alshammari GM, AlTamimi JZ, AlMousa LA, AlKehayez NM, Aljabryn DH, Alagal RI, Yahya MA. The protective effect of shrimp cooked in different methods on high-cholesterol- induced fatty liver in rats. Saudi J Biol Sci 2021; 28:170-182. [PMID: 33424294 PMCID: PMC7783650 DOI: 10.1016/j.sjbs.2020.09.036] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/03/2020] [Revised: 08/24/2020] [Accepted: 09/17/2020] [Indexed: 11/25/2022] Open
Abstract
This study examined the impact of different cooking methods on fatty acid (FAs) composition of shrimp meat and the ability of these foods to protect against high cholesterol (HC) diet-induced non-alcoholic fatty liver disease (NAFLD) in rats. Shrimp were cooked for 10 min boiled, grilled, or fried in sunflower oil. Rats (n = 6/group) were fed a normal diet (ND)or high-cholesterol diet (HC) each containing boiled, grilled or fried shrimp powder (15% w/w) (NDBS, NDFS, NDGS for ND or HCBS, HCFS, HCDGS for HC diet). Frying alone significantly reduced total levels of saturated FAs (SFA) and increased total mono- and polyunsaturated FAs (MSFA, and PUFAs, respectively) in shrimp meat. It also increased levels of n-6 PUFAs and linoleic acid (LA) and decreased levels of n-3 PUFAs including eicosapentaenoic FAs (EPA) and docosahexaenoic fatty acid (DHA). When fed to HC rats, only diets containing the grilled and boiled shrimp powders significantly prevented the weight loss, lowered fasting and glucose levels, improved glucose and insulin tolerance, and prevented the increase in serum liver markers, ALT and AST. They also reduced hepatic fat accumulation, reduced serum levels and hepatic levels of cholesterol and triglycerides (TGs), reduced hepatic levels of MDA, tumor necrosis factor-alpha (TNF-α), and IL-6, and increased those of glutathione (GSH) and superoxide dismutase (SOD). No alterations in all these parameters were observed in HC-fed rats which fed fried shrimp. In conclusion, boiling and grilling but not frying are the best method to cook shrimp to preserve their fatty acid content and its nutritional value in ameliorating NAFLD.
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Affiliation(s)
- Nora A AlFaris
- Department of Physical Sport Science, Princess Nourah bint Abdulrahman University, Riyadh, Saudi Arabia
| | - Ghedeir M Alshammari
- Department of Food Science and Nutrition, College of Food and Agricultural Science, King Saud University, Riyadh, Saudi Arabia
| | - Jozaa Z AlTamimi
- Department of Physical Sport Science, Princess Nourah bint Abdulrahman University, Riyadh, Saudi Arabia
| | - Lujain A AlMousa
- Department of Physical Sport Science, Princess Nourah bint Abdulrahman University, Riyadh, Saudi Arabia
| | - Nora M AlKehayez
- Department of Physical Sport Science, Princess Nourah bint Abdulrahman University, Riyadh, Saudi Arabia
| | - Dalal H Aljabryn
- Department of Physical Sport Science, Princess Nourah bint Abdulrahman University, Riyadh, Saudi Arabia
| | - Reham I Alagal
- Department of Physical Sport Science, Princess Nourah bint Abdulrahman University, Riyadh, Saudi Arabia
| | - Mohammed A Yahya
- Department of Food Science and Nutrition, College of Food and Agricultural Science, King Saud University, Riyadh, Saudi Arabia
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Yan J, Wang D, Meng Z, Yan S, Teng M, Jia M, Li R, Tian S, Weiss C, Zhou Z, Zhu W. Effects of incremental endosulfan sulfate exposure and high fat diet on lipid metabolism, glucose homeostasis and gut microbiota in mice. ENVIRONMENTAL POLLUTION (BARKING, ESSEX : 1987) 2021; 268:115697. [PMID: 33070067 DOI: 10.1016/j.envpol.2020.115697] [Citation(s) in RCA: 16] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 05/18/2020] [Revised: 08/29/2020] [Accepted: 09/17/2020] [Indexed: 06/11/2023]
Abstract
The influence of pollutants on metabolic diseases such as type 2 diabetes mellitus is an emerging field in environmental medicine. Here, we explored the effects of a low-dose endosulfan sulfate (ES), a major metabolite of the pesticide endosulfan and a bio-persistent contaminant detected in environmental and human samples, on the progress of obesity and metabolic disorders. Pregnant CD-1 mice were given ES from gestational day 6 to postnatal day 21 (short-term). After weaning, male pups of exposed dams were provided with a low-fat or a high-fat diet (LFD or HFD) and assessed after an additional 12 weeks. At the same time, one group of male pups continuously received ES (long-term). Treatment with low-dose ES, short or long-term, alleviated the development of obesity and accumulation of hepatic triglycerides induced by HFD. Analysis of gene expression, metabolic profile and gut microbiome indicates that ES treatment inhibits adipogenesis induced by HFD due to enhanced lipid catabolism, fatty acid oxidation and disturbance of gut microbiota composition. However, impaired glucose and insulin homeostasis were still conserved in HFD-fed mice exposed to ES. Furthermore, ES treatment impaired glucose tolerance, affected hepatic gene expression, fatty acids composition and serum metabolic profile, as well as disturbed gut microbiota in LFD-fed mice. In conclusion, ES treatment at levels close to the accepted daily intake during fetal development directly impact glucose homeostasis, hepatic lipid metabolism, and gut microbiome dependent on the type of diet consumed. These findings provide a better understanding of the complex interactions of environmental pollutants and diet at early life stages also in the context of metabolic disease.
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Affiliation(s)
- Jin Yan
- Beijing Advanced Innovation Center for Food Nutrition and Human Health, Department of Applied Chemistry, China Agricultural University, Beijing, 100193, China
| | - Dezhen Wang
- Beijing Advanced Innovation Center for Food Nutrition and Human Health, Department of Applied Chemistry, China Agricultural University, Beijing, 100193, China
| | - Zhiyuan Meng
- Beijing Advanced Innovation Center for Food Nutrition and Human Health, Department of Applied Chemistry, China Agricultural University, Beijing, 100193, China
| | - Sen Yan
- Beijing Advanced Innovation Center for Food Nutrition and Human Health, Department of Applied Chemistry, China Agricultural University, Beijing, 100193, China
| | - Miaomiao Teng
- Beijing Advanced Innovation Center for Food Nutrition and Human Health, Department of Applied Chemistry, China Agricultural University, Beijing, 100193, China
| | - Ming Jia
- Beijing Advanced Innovation Center for Food Nutrition and Human Health, Department of Applied Chemistry, China Agricultural University, Beijing, 100193, China
| | - Ruisheng Li
- Beijing Advanced Innovation Center for Food Nutrition and Human Health, Department of Applied Chemistry, China Agricultural University, Beijing, 100193, China
| | - Sinuo Tian
- Beijing Advanced Innovation Center for Food Nutrition and Human Health, Department of Applied Chemistry, China Agricultural University, Beijing, 100193, China
| | - Carsten Weiss
- Institute of Biological and Chemical Systems - Biological Information Processing, Karlsruhe Institute of Technology, Campus North, Hermann-von-Helmholtz-Platz 1, 76344, Eggenstein-Leopoldshafen, Germany
| | - Zhiqiang Zhou
- Beijing Advanced Innovation Center for Food Nutrition and Human Health, Department of Applied Chemistry, China Agricultural University, Beijing, 100193, China
| | - Wentao Zhu
- Beijing Advanced Innovation Center for Food Nutrition and Human Health, Department of Applied Chemistry, China Agricultural University, Beijing, 100193, China.
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Cansanção K, Citelli M, Carvalho Leite N, López de las Hazas MC, Dávalos A, Tavares do Carmo MDG, Peres WAF. Impact of Long-Term Supplementation with Fish Oil in Individuals with Non-Alcoholic Fatty Liver Disease: A Double Blind Randomized Placebo Controlled Clinical Trial. Nutrients 2020; 12:nu12113372. [PMID: 33147705 PMCID: PMC7693661 DOI: 10.3390/nu12113372] [Citation(s) in RCA: 16] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/09/2020] [Revised: 10/27/2020] [Accepted: 10/30/2020] [Indexed: 02/06/2023] Open
Abstract
Non-alcoholic fatty liver disease (NAFLD) is a chronic disease affecting up to 25% of the population worldwide. n-3 long-chain polyunsaturated fatty acids (n-3 PUFA) have been associated with improved clinical parameters of NAFLD. Our purpose was to conduct a pilot study to evaluate the effects of n-3 PUFA supplementation in a randomized, double-blind, placebo-controlled clinical study performed on NAFLD individuals diagnosed by ultrasound. Patients received n-3 PUFA (n = 13) or placebo (n = 11) supplementation for six months. Circulating miR-122 expression (determined by quantitative real time-polymerase chain reaction (qRT-PCR), liver fibrosis (FibroScan®), red blood cells (RBC) fatty acids (gas chromatography), and biochemical tests were performed at baseline and after intervention. After the intervention, in the n-3 PUFA group, docosahexaenoic acid (DHA) and omega index increased significantly in RBC (p = 0.022 and p = 0.012, respectively), in addition to a significant reduction in alkaline phosphatase (ALP) (p = 0.002) and liver fibrosis (p = 0.039). However, there was no change in the expression of circulating miR-122 in both groups. Our results showed that omega-3 PUFA were incorporated in erythrocytes after six months of fish oil supplementary intake, and that n-3 PUFA were effective in reducing ALP and liver fibrosis without altering the expression of circulating miR-122 in individuals with NAFLD.
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Affiliation(s)
- Kátia Cansanção
- Institute of Nutrition Josué de Castro of Federal University of Rio de Janeiro (UFRJ), Rio de Janeiro 21.941-902, Brazil; (K.C.); (M.d.G.T.d.C.)
| | - Marta Citelli
- Instituto de Nutrição, Universidade do Estado do Rio de Janeiro, Rio de Janeiro 20559-900, Brazil;
| | - Nathalie Carvalho Leite
- Department of Internal Medicine, University Hospital Clementino Fraga Filho, School of Medicine of UFRJ, Rio de Janeiro 21.941-902, Brazil;
| | - María-Carmen López de las Hazas
- Laboratory of Epigenetics of Lipid Metabolism, Madrid Institute for Advanced Studies (IMDEA)-Food, CEI UAM+CSIC, 28049 Madrid, Spain; (M-C.L.d.l.H.); (A.D.)
| | - Alberto Dávalos
- Laboratory of Epigenetics of Lipid Metabolism, Madrid Institute for Advanced Studies (IMDEA)-Food, CEI UAM+CSIC, 28049 Madrid, Spain; (M-C.L.d.l.H.); (A.D.)
| | - Maria das Graças Tavares do Carmo
- Institute of Nutrition Josué de Castro of Federal University of Rio de Janeiro (UFRJ), Rio de Janeiro 21.941-902, Brazil; (K.C.); (M.d.G.T.d.C.)
| | - Wilza Arantes Ferreira Peres
- Institute of Nutrition Josué de Castro of Federal University of Rio de Janeiro (UFRJ), Rio de Janeiro 21.941-902, Brazil; (K.C.); (M.d.G.T.d.C.)
- Correspondence: ; Tel.: +55-21-393864-32
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Valenzuela R, Ortiz M, Hernández-Rodas MC, Echeverría F, Videla LA. Targeting n-3 Polyunsaturated Fatty Acids in Non-Alcoholic Fatty Liver Disease. Curr Med Chem 2020; 27:5250-5272. [PMID: 30968772 DOI: 10.2174/0929867326666190410121716] [Citation(s) in RCA: 39] [Impact Index Per Article: 7.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/18/2018] [Revised: 12/14/2018] [Accepted: 01/12/2019] [Indexed: 02/06/2023]
Abstract
BACKGROUND Non-Alcoholic Fatty Liver Disease (NAFLD) is characterized by abnormal hepatic accumulation of triacylglycerides in the absence of alcohol consumption, in association with Oxidative Stress (OS), a pro-inflammatory state and Insulin Resistance (IR), which are attenuated by n-3 long-chain polyunsaturated Fatty Acids (FAs) C20-C22 (LCPUFAs) supplementation. Main causes of NAFLD comprise high caloric intake and a sedentary lifestyle, with high intakes of saturated FAs. METHODS The review includes several searches considering the effects of n-3 LCPUFAs in NAFLD in vivo and in vitro models, using the PubMed database from the National Library of Medicine- National Institutes of Health. RESULT The LCPUFAs eicosapentaenoic acid (C20:5 n-3, EPA) and docosahexaenoic acid (C22:6 n- 3, DHA) have a positive effect in diminishing liver steatosis, OS, and the levels of aspartate aminotransferase, alanine aminotransferase and pro-inflammatory cytokines, with improvement of insulin sensitivity and adiponectin levels. The molecular pathways described for n-3 LCPUFAs in cellular and animal models and humans include peroxisome proliferator-activated receptor-α activation favouring FA oxidation, diminution of lipogenesis due to sterol responsive element binding protein-1c downregulation and inflammation resolution. Besides, nuclear factor erythroid-2-related factor-2 activation is elicited by n-3 LCPUFA-derived oxidation products producing direct and indirect antioxidant responses, with concomitant anti-fibrogenic action. CONCLUSION The discussed effects of n-3 LCPUFA supplementation support its use in NAFLD, although having a limited value in NASH, a contention that may involve n-3 LCPUFA oxygenated derivatives. Clinical trials establishing optimal dosages, intervention times, type of patients and possible synergies with other natural products are needed in future studies.
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Affiliation(s)
- Rodrigo Valenzuela
- Department of Nutrition, Faculty of Medicine, University of Chile, Av. Independencia 1027, Independencia, Santiago 8380453, Chile
| | - Macarena Ortiz
- Nutrition and Dietetics School, Faculty of Health Sciences, Catholic University of Maule, Merced 333, Curicó 3340000, Chile
| | - María Catalina Hernández-Rodas
- Department of Nutrition, Faculty of Medicine, University of Chile, Av. Independencia 1027, Independencia, Santiago 8380453, Chile
| | - Francisca Echeverría
- Department of Nutrition, Faculty of Medicine, University of Chile, Av. Independencia 1027, Independencia, Santiago 8380453, Chile
| | - Luis Alberto Videla
- Molecular and Clinical Pharmacology Program, Institute of Biomedical Sciences, Faculty of Medicine, University of Chile, Av. Independencia 1027, Independencia, Santiago 8380453, Chile
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Aktary ML, Eller LK, Nicolucci AC, Reimer RA. Cross-sectional analysis of the health profile and dietary intake of a sample of Canadian adults diagnosed with non-alcoholic fatty liver disease. Food Nutr Res 2020; 64:4548. [PMID: 33061886 PMCID: PMC7534951 DOI: 10.29219/fnr.v64.4548] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/20/2020] [Revised: 07/27/2020] [Accepted: 08/07/2020] [Indexed: 12/11/2022] Open
Abstract
Background Dietary intake is an important factor in the development and management of non-alcoholic fatty liver disease (NAFLD); however, optimal dietary composition remains unclear. Moreover, there is minimal evidence on the relationship between dietary intake and markers of liver health in Canadian adults diagnosed with NAFLD. Objective The aim of this study is to characterize the dietary intake of a sample of Canadian adults diagnosed with NAFLD and examine the correlations with markers of liver health. Design Forty-two adults recruited from the community and hepatology clinics in Calgary, Canada from 2016 to 2019 completed a 3-day food record. Anthropometrics, blood biomarkers, liver stiffness (FibroScan), and liver fat (magnetic resonance imaging) were measured. Nutrient intake was compared with the data from the 2004 and 2015 Canadian Community Health Surveys. Relationships were assessed using Pearson’s correlation and regression analysis. Results Relative to Canadian dietary recommendations, participants consumed lower magnesium, fiber, calcium, vitamin D, and vitamin E, and higher cholesterol, saturated fat, total fat, fructose, iron, vitamin B12, selenium, phosphorus, and sodium. Compared with the national average, participants consumed more energy, fiber, sodium, total fat, and saturated fat. Systolic blood pressure (P = 0.012), serum α-2 macroglobulin (P = 0.008), carbohydrate (P = 0.022), total fat (P = 0.029), and saturated fat intakes (P = 0.029) were associated with FibroScan scores. Liver fat was correlated with serum triglycerides (P < 0.001), trunk fat (P = 0.029), added sugar (P = 0.042), phosphorus (P = 0.017), and magnesium intake (P = 0.013). In females, selenium intake was associated with liver fat (P = 0.015) and FibroScan score (P = 0.05), while in males, liver fat was associated with trunk fat (P = 0.004), body weight (P = 0.004), high-density lipoprotein (P < 0.001), and fructose intake (P = 0.037). Regression analysis showed that increasing magnesium intake corresponds to a decrease in liver fat. Conclusion Despite the higher energy intake of participants, overall nutrient intake is low, suggesting lower diet quality. Associations between select micronutrients and liver health markers warrant further investigation.
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Affiliation(s)
| | - Lindsay K Eller
- Faculty of Kinesiology, University of Calgary, Calgary, Canada
| | | | - Raylene A Reimer
- Faculty of Kinesiology, University of Calgary, Calgary, Canada.,Department of Biochemistry and Molecular Biology, Cumming School of Medicine, University of Calgary, Calgary, Canada
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Lee CH, Fu Y, Yang SJ, Chi CC. Effects of Omega-3 Polyunsaturated Fatty Acid Supplementation on Non-Alcoholic Fatty Liver: A Systematic Review and Meta-Analysis. Nutrients 2020; 12:nu12092769. [PMID: 32932796 PMCID: PMC7551292 DOI: 10.3390/nu12092769] [Citation(s) in RCA: 81] [Impact Index Per Article: 16.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/08/2020] [Revised: 09/06/2020] [Accepted: 09/08/2020] [Indexed: 02/06/2023] Open
Abstract
(1) Aim: Non-alcoholic fatty liver disease (NAFLD) is a prevalent disease worldwide. Omega-3 polyunsaturated fatty acids (n-3 PUFAs) bear anti-inflammatory action and can ameliorate hyperlipidemia. We wish to appraise the effects of n-3 PUFAs supplement on NAFLD. (2) Methods: We searched CENTRAL, Embase, and MEDLINE on 29 March 2020 for randomized control trials (RCTs) on the effects of n-3 PUFAs supplementation in treating NAFLD. The Cochrane Collaboration's tool was used to assess the risk of bias of included RCTs. (3) Results: We included 22 RCTs with 1366 participants. The risk of bias of included RCTs was generally low or unclear. n-3 PUFAs supplementation significantly reduced liver fat compared with placebo (pooled risk ratio 1.52; 95% confidence interval (CI) 1.09 to 2.13). n-3 PUFAs supplementation also significantly improved the levels of triglyceride, total cholesterol, high-density lipoprotein, and body-mass index, with pooled mean difference and 95% CI being -28.57 (-40.81 to -16.33), -7.82 (-14.86 to -0.79), 3.55 (1.38 to 5.73), and -0.46 (-0.84 to -0.08), respectively. (4) Conclusions: The current evidence supports the effects of n-3 PUFAs supplementation in improving fatty liver. n-3 PUFAs supplementation may also improve blood lipid levels and obesity.
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Affiliation(s)
- Cheng-Han Lee
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Chang Gung Memorial Hospital, Linkou, Taoyuan 33305, Taiwan;
| | - Yun Fu
- Department of Dermatology, Chang Gung Memorial Hospital, Linkou, Taoyuan 33305, Taiwan;
| | - Shih-Jyun Yang
- Department of Dermatology, Chang Gung Memorial Hospital, Keelung 20401, Taiwan;
| | - Ching-Chi Chi
- Department of Dermatology, Chang Gung Memorial Hospital, Linkou, Taoyuan 33305, Taiwan;
- College of Medicine, Chang Gung University, Taoyuan 33302, Taiwan
- Correspondence: ; Tel.: +886-3-328-1200 (ext. 3556)
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Lam S, Doran S, Yuksel HH, Altay O, Turkez H, Nielsen J, Boren J, Uhlen M, Mardinoglu A. Addressing the heterogeneity in liver diseases using biological networks. Brief Bioinform 2020; 22:1751-1766. [PMID: 32201876 PMCID: PMC7986590 DOI: 10.1093/bib/bbaa002] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/15/2019] [Revised: 11/28/2019] [Accepted: 01/03/2020] [Indexed: 12/19/2022] Open
Abstract
The abnormalities in human metabolism have been implicated in the progression of several complex human diseases, including certain cancers. Hence, deciphering the underlying molecular mechanisms associated with metabolic reprogramming in a disease state can greatly assist in elucidating the disease aetiology. An invaluable tool for establishing connections between global metabolic reprogramming and disease development is the genome-scale metabolic model (GEM). Here, we review recent work on the reconstruction of cell/tissue-type and cancer-specific GEMs and their use in identifying metabolic changes occurring in response to liver disease development, stratification of the heterogeneous disease population and discovery of novel drug targets and biomarkers. We also discuss how GEMs can be integrated with other biological networks for generating more comprehensive cell/tissue models. In addition, we review the various biological network analyses that have been employed for the development of efficient treatment strategies. Finally, we present three case studies in which independent studies converged on conclusions underlying liver disease.
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Affiliation(s)
- Simon Lam
- Centre for Host-Microbiome Interactions, Faculty of Dentistry, Oral & Craniofacial Sciences, King's College London, London, SE1 9RT, United Kingdom; Science for Life Laboratory, KTH - Royal Institute of Technology, Stockholm, SE-17121, Sweden
| | - Stephen Doran
- Centre for Host-Microbiome Interactions, Faculty of Dentistry, Oral & Craniofacial Sciences, King's College London, London, SE1 9RT, United Kingdom; Science for Life Laboratory, KTH - Royal Institute of Technology, Stockholm, SE-17121, Sweden
| | - Hatice Hilal Yuksel
- Centre for Host-Microbiome Interactions, Faculty of Dentistry, Oral & Craniofacial Sciences, King's College London, London, SE1 9RT, United Kingdom; Science for Life Laboratory, KTH - Royal Institute of Technology, Stockholm, SE-17121, Sweden
| | - Ozlem Altay
- Centre for Host-Microbiome Interactions, Faculty of Dentistry, Oral & Craniofacial Sciences, King's College London, London, SE1 9RT, United Kingdom; Science for Life Laboratory, KTH - Royal Institute of Technology, Stockholm, SE-17121, Sweden
| | - Hasan Turkez
- Centre for Host-Microbiome Interactions, Faculty of Dentistry, Oral & Craniofacial Sciences, King's College London, London, SE1 9RT, United Kingdom; Science for Life Laboratory, KTH - Royal Institute of Technology, Stockholm, SE-17121, Sweden
| | - Jens Nielsen
- Centre for Host-Microbiome Interactions, Faculty of Dentistry, Oral & Craniofacial Sciences, King's College London, London, SE1 9RT, United Kingdom; Science for Life Laboratory, KTH - Royal Institute of Technology, Stockholm, SE-17121, Sweden
| | - Jan Boren
- Centre for Host-Microbiome Interactions, Faculty of Dentistry, Oral & Craniofacial Sciences, King's College London, London, SE1 9RT, United Kingdom; Science for Life Laboratory, KTH - Royal Institute of Technology, Stockholm, SE-17121, Sweden
| | - Mathias Uhlen
- Centre for Host-Microbiome Interactions, Faculty of Dentistry, Oral & Craniofacial Sciences, King's College London, London, SE1 9RT, United Kingdom; Science for Life Laboratory, KTH - Royal Institute of Technology, Stockholm, SE-17121, Sweden
| | - Adil Mardinoglu
- Centre for Host-Microbiome Interactions, Faculty of Dentistry, Oral & Craniofacial Sciences, King's College London, London, SE1 9RT, United Kingdom; Science for Life Laboratory, KTH - Royal Institute of Technology, Stockholm, SE-17121, Sweden
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Sofyana NT, Zheng J, Manabe Y, Yamamoto Y, Kishino S, Ogawa J, Sugawara T. Gut microbial fatty acid metabolites (KetoA and KetoC) affect the progression of nonalcoholic steatohepatitis and reverse cholesterol transport metabolism in mouse model. Lipids 2020; 55:151-162. [PMID: 32040876 DOI: 10.1002/lipd.12219] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/20/2019] [Revised: 01/22/2020] [Accepted: 01/23/2020] [Indexed: 01/05/2023]
Abstract
Nonalcoholic steatohepatitis (NASH) is a common liver disease that occurs in both alcoholics and nonalcoholics. Oxidative stress is a possible causative factor for liver diseases including NASH. Gut microorganisms, especially lactic acid bacteria, can produce unique fatty acids, including hydroxy, oxo, conjugated, and partially saturated fatty acids. The oxo fatty acid 10-oxo-11(E)-octadecenoic acid (KetoC) provides potent cytoprotective effects against oxidative stress through activation of Nrf2-ARE pathway. The aim of this study was to explore the preventive and therapeutic effects of gut microbial fatty acid metabolites in a NASH mouse model. The mice were divided into 3 experimental groups and fed as follows: (1) high-fat diet (HFD) (2) HFD mixed with 0.1% KetoA (10-oxo-12(Z)-octadecenoic acid), and (3) HFD mixed with 0.1% KetoC. After 3 weeks of feeding, plasma parameters, liver histology, and mRNA expression of multiple genes were assessed. There was hardly any difference in fat accumulation in the histological study; however, no ballooning occurred in 2/5 mice of KetoC group. Bridging fibrosis was not observed in the KetoA group, although KetoA administration did not significantly suppress fibrosis score (p = 0.10). In addition, KetoC increased the expression level of HDL related genes and HDL cholesterol levels in the plasma. These results indicated that KetoA and KetoC may partly affect the progression of NASH in mice models.
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Affiliation(s)
- Neng Tanty Sofyana
- Division of Applied Bioscience, Graduate School of Agriculture, Kyoto University, Kitashirakawa Oiwake-cho, Sakyo-ku, Kyoto, 606-8502, Japan
| | - Jiawen Zheng
- Division of Applied Bioscience, Graduate School of Agriculture, Kyoto University, Kitashirakawa Oiwake-cho, Sakyo-ku, Kyoto, 606-8502, Japan
| | - Yuki Manabe
- Division of Applied Bioscience, Graduate School of Agriculture, Kyoto University, Kitashirakawa Oiwake-cho, Sakyo-ku, Kyoto, 606-8502, Japan
| | - Yuta Yamamoto
- Department of Anatomy and Cell Biology, Wakayama Medical University, 580 Mikazura, Wakayama-shi, 641-0011, Japan
| | - Shigenobu Kishino
- Division of Applied Life Sciences, Graduate School of Agriculture, Kyoto University, Kitashirakawa Oiwake-cho, Sakyo-ku, Kyoto, 606-8502, Japan
| | - Jun Ogawa
- Division of Applied Life Sciences, Graduate School of Agriculture, Kyoto University, Kitashirakawa Oiwake-cho, Sakyo-ku, Kyoto, 606-8502, Japan
| | - Tatsuya Sugawara
- Division of Applied Bioscience, Graduate School of Agriculture, Kyoto University, Kitashirakawa Oiwake-cho, Sakyo-ku, Kyoto, 606-8502, Japan
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Musa-Veloso K, Venditti C, Lee HY, Darch M, Floyd S, West S, Simon R. Systematic review and meta-analysis of controlled intervention studies on the effectiveness of long-chain omega-3 fatty acids in patients with nonalcoholic fatty liver disease. Nutr Rev 2019; 76:581-602. [PMID: 29917092 PMCID: PMC6367993 DOI: 10.1093/nutrit/nuy022] [Citation(s) in RCA: 78] [Impact Index Per Article: 13.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
Context Treatment options for nonalcoholic fatty liver disease (NAFLD) are needed. Objective The aim of this review was to systematically assess the effects of omega-3 long-chain
polyunsaturated fatty acids (n-3 LC-PUFAs), particularly eicosapentaenoic acid and
docosahexaenoic acid, on liver-related and metabolic outcomes in adult and pediatric
patients with NAFLD. Data Sources The online information service ProQuest Dialog was used to search 8 literature
databases. Study Selection Controlled intervention studies in which the independent effects of n-3 LC-PUFAs could
be isolated were eligible for inclusion. Data Extraction The 18 unique studies that met the criteria for inclusion were divided into 2 sets, and
data transcriptions and study quality assessments were conducted in duplicate. Each
effect size was expressed as the weighted mean difference and 95%CI, using a
random-effects model and the inverse of the variance as a weighting factor. Results Based on the meta-analyses, supplementation with n-3 LC-PUFAs resulted in statistically
significant improvements in 6 of 13 metabolic risk factors, in levels of 2 of 3 liver
enzymes, in liver fat content (assessed via magnetic resonance imaging/spectroscopy),
and in steatosis score (assessed via ultrasonography). Histological measures of disease
[which were assessed only in patients with nonalcoholic steatohepatitis (NASH)] were
unaffected by n-3 LC-PUFA supplementation. Conclusions Omega-3 LC-PUFAs are useful in the dietary management of patients with NAFLD.
Additional trials are needed to better understand the effects of n-3 LC-PUFAs on
histological outcomes in patients with NASH. Systematic Review Registration PROSPERO CRD42017055951.
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Affiliation(s)
- Kathy Musa-Veloso
- Intertek Scientific & Regulatory Consultancy, Health, Environmental & Regulatory Services (HERS), Mississauga, Ontario, Canada
| | - Carolina Venditti
- Intertek Scientific & Regulatory Consultancy, Health, Environmental & Regulatory Services (HERS), Mississauga, Ontario, Canada
| | - Han Youl Lee
- Intertek Scientific & Regulatory Consultancy, Health, Environmental & Regulatory Services (HERS), Mississauga, Ontario, Canada
| | - Maryse Darch
- Intertek Scientific & Regulatory Consultancy, Health, Environmental & Regulatory Services (HERS), Mississauga, Ontario, Canada
| | - Seth Floyd
- Intertek Scientific & Regulatory Consultancy, Health, Environmental & Regulatory Services (HERS), Mississauga, Ontario, Canada
| | - Spencer West
- Intertek Scientific & Regulatory Consultancy, Health, Environmental & Regulatory Services (HERS), Mississauga, Ontario, Canada
| | - Ryan Simon
- Intertek Scientific & Regulatory Consultancy, Health, Environmental & Regulatory Services (HERS), Mississauga, Ontario, Canada
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Abstract
Non-alcoholic fatty liver disease is the most common cause of chronic liver disease in the developed world and commonly associated with metabolic comorbidities such as diabetes mellitus, hypertension, dyslipidemia, and obesity. Non-alcoholic steatohepatitis is an aggressive form of non-alcoholic fatty liver disease, associated with an increased risk of liver and non-liver-related mortality. Currently there are no approved therapies for non-alcoholic fatty liver disease/non-alcoholic steatohepatitis and standard-of-care lifestyle advice is rarely effective. This has spurned intense drug development efforts and several agents are in clinical trials to address this major gap in non-alcoholic fatty liver disease. Drug development efforts have focused on pathogenic mechanisms including pathways involving lipid metabolism, inflammation, and fibrosis. This review presents the overview of the trials and agents in the pipeline of emerging therapies for non-alcoholic fatty liver disease/non-alcoholic steatohepatitis.
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Affiliation(s)
- Samarth Siddharth Patel
- Division of Gastroenterology, Hepatology and Nutrition, Department of Internal Medicine, Virginia Commonwealth University, MCV Box 980342, Richmond, VA, 23298-0342, USA
| | - Mohammad Shadab Siddiqui
- Division of Gastroenterology, Hepatology and Nutrition, Department of Internal Medicine, Virginia Commonwealth University, MCV Box 980342, Richmond, VA, 23298-0342, USA.
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Orang Z, Mozaffari-Khosravi H, Sivandzadeh G, Pantovic A. The effect of omega-3 supplementation on glycemic indices and lipid profile in type 2 diabetic patients with non-alcoholic fatty liver disease: A double-blind, randomized, clinical trial. MEDITERRANEAN JOURNAL OF NUTRITION AND METABOLISM 2019. [DOI: 10.3233/mnm-180265] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/22/2022]
Affiliation(s)
- Zahra Orang
- Department of Nutrition, School of Public Health, Shahid Sadoughi University of Medical Sciences, Yazd, Iran
| | - Hassan Mozaffari-Khosravi
- Department of Nutrition, School of Public Health, Shahid Sadoughi University of Medical Sciences, Yazd, Iran
| | - GholamReza Sivandzadeh
- Department of Internal Medicine, Gastroenterohepatology Research Center, Shiraz University of Medical Sciences, Shiraz, Iran
| | - Ana Pantovic
- Centre of Research Excellence in Nutrition and Metabolism, Institute for Medical Research, University of Belgrade, Serbia
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Marchisello S, Di Pino A, Scicali R, Urbano F, Piro S, Purrello F, Rabuazzo AM. Pathophysiological, Molecular and Therapeutic Issues of Nonalcoholic Fatty Liver Disease: An Overview. Int J Mol Sci 2019; 20:ijms20081948. [PMID: 31010049 PMCID: PMC6514656 DOI: 10.3390/ijms20081948] [Citation(s) in RCA: 130] [Impact Index Per Article: 21.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/22/2019] [Revised: 04/18/2019] [Accepted: 04/20/2019] [Indexed: 12/12/2022] Open
Abstract
Nonalcoholic Fatty Liver Disease (NAFLD) represents the leading cause of liver disease in developed countries but its diffusion is currently also emerging in Asian countries, in South America and in other developing countries. It is progressively becoming one of the main diseases responsible for hepatic insufficiency, hepatocarcinoma and the need for orthotopic liver transplantation. NAFLD is linked with metabolic syndrome in a close and bidirectional relationship. To date, NAFLD is a diagnosis of exclusion, and liver biopsy is the gold standard for diagnosis. NAFLD pathogenesis is complex and multifactorial, mainly involving genetic, metabolic and environmental factors. New concepts are constantly arising in the literature promising new diagnostic and therapeutic tools. One of the challenges will be to better characterize not only NAFLD development but overall NAFLD progression, in order to better identify NAFLD patients at higher risk of metabolic, cardiovascular and neoplastic complications. This review analyses NAFLD epidemiology and the different prevalence of the disease in distinct groups, particularly according to sex, age, body mass index, type 2 diabetes and dyslipidemia. Furthermore, the work expands on the pathophysiology of NAFLD, examining multiple-hit pathogenesis and the role of different factors in hepatic steatosis development and progression: genetics, metabolic factors and insulin resistance, diet, adipose tissue, gut microbiota, iron deposits, bile acids and circadian clock. In conclusion, the current available therapies for NAFLD will be discussed.
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Affiliation(s)
- Simona Marchisello
- Department of Clinical and Molecular Medicine, University of Catania, Catania 95100, Italy.
| | - Antonino Di Pino
- Department of Clinical and Molecular Medicine, University of Catania, Catania 95100, Italy.
| | - Roberto Scicali
- Department of Clinical and Molecular Medicine, University of Catania, Catania 95100, Italy.
| | - Francesca Urbano
- Department of Clinical and Molecular Medicine, University of Catania, Catania 95100, Italy.
| | - Salvatore Piro
- Department of Clinical and Molecular Medicine, University of Catania, Catania 95100, Italy.
| | - Francesco Purrello
- Department of Clinical and Molecular Medicine, University of Catania, Catania 95100, Italy.
| | - Agata Maria Rabuazzo
- Department of Clinical and Molecular Medicine, University of Catania, Catania 95100, Italy.
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Yang J, Fernández-Galilea M, Martínez-Fernández L, González-Muniesa P, Pérez-Chávez A, Martínez JA, Moreno-Aliaga MJ. Oxidative Stress and Non-Alcoholic Fatty Liver Disease: Effects of Omega-3 Fatty Acid Supplementation. Nutrients 2019; 11:E872. [PMID: 31003450 PMCID: PMC6521137 DOI: 10.3390/nu11040872] [Citation(s) in RCA: 183] [Impact Index Per Article: 30.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/29/2019] [Revised: 04/12/2019] [Accepted: 04/15/2019] [Indexed: 02/06/2023] Open
Abstract
Aging is a complex phenomenon characterized by the progressive loss of tissue and organ function. The oxidative-stress theory of aging postulates that age-associated functional losses are due to the accumulation of ROS-induced damage. Liver function impairment and non-alcoholic fatty liver disease (NAFLD) are common among the elderly. NAFLD can progress to non-alcoholic steatohepatitis (NASH) and evolve to hepatic cirrhosis or hepatic carcinoma. Oxidative stress, lipotoxicity, and inflammation play a key role in the progression of NAFLD. A growing body of evidence supports the therapeutic potential of omega-3 polyunsaturated fatty acids (n-3 PUFA), mainly docosahaexenoic (DHA) and eicosapentaenoic acid (EPA), on metabolic diseases based on their antioxidant and anti-inflammatory properties. Here, we performed a systematic review of clinical trials analyzing the efficacy of n-3 PUFA on both systemic oxidative stress and on NAFLD/NASH features in adults. As a matter of fact, it remains controversial whether n-3 PUFA are effective to counteract oxidative stress. On the other hand, data suggest that n-3 PUFA supplementation may be effective in the early stages of NAFLD, but not in patients with more severe NAFLD or NASH. Future perspectives and relevant aspects that should be considered when planning new randomized controlled trials are also discussed.
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Affiliation(s)
- Jinchunzi Yang
- Centre for Nutrition Research, School of Pharmacy and Nutrition, University of Navarra, 31008 Pamplona, Spain.
| | - Marta Fernández-Galilea
- Centre for Nutrition Research, School of Pharmacy and Nutrition, University of Navarra, 31008 Pamplona, Spain.
- Department of Nutrition, Food Science and Physiology, School of Pharmacy and Nutrition, University of Navarra, 31008 Pamplona, Spain.
- IDISNA, Navarra's Health Research Institute, 31008 Pamplona, Spain.
| | - Leyre Martínez-Fernández
- Centre for Nutrition Research, School of Pharmacy and Nutrition, University of Navarra, 31008 Pamplona, Spain.
| | - Pedro González-Muniesa
- Centre for Nutrition Research, School of Pharmacy and Nutrition, University of Navarra, 31008 Pamplona, Spain.
- Department of Nutrition, Food Science and Physiology, School of Pharmacy and Nutrition, University of Navarra, 31008 Pamplona, Spain.
- IDISNA, Navarra's Health Research Institute, 31008 Pamplona, Spain.
- CIBERobn Physiopathology of Obesity and Nutrition, Centre of Biomedical Research Network, ISCIII, 28029 Madrid, Spain.
| | - Adriana Pérez-Chávez
- Centre for Nutrition Research, School of Pharmacy and Nutrition, University of Navarra, 31008 Pamplona, Spain.
| | - J Alfredo Martínez
- Centre for Nutrition Research, School of Pharmacy and Nutrition, University of Navarra, 31008 Pamplona, Spain.
- Department of Nutrition, Food Science and Physiology, School of Pharmacy and Nutrition, University of Navarra, 31008 Pamplona, Spain.
- IDISNA, Navarra's Health Research Institute, 31008 Pamplona, Spain.
- CIBERobn Physiopathology of Obesity and Nutrition, Centre of Biomedical Research Network, ISCIII, 28029 Madrid, Spain.
| | - Maria J Moreno-Aliaga
- Centre for Nutrition Research, School of Pharmacy and Nutrition, University of Navarra, 31008 Pamplona, Spain.
- Department of Nutrition, Food Science and Physiology, School of Pharmacy and Nutrition, University of Navarra, 31008 Pamplona, Spain.
- IDISNA, Navarra's Health Research Institute, 31008 Pamplona, Spain.
- CIBERobn Physiopathology of Obesity and Nutrition, Centre of Biomedical Research Network, ISCIII, 28029 Madrid, Spain.
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Chen ZY, Liu M, Jing LP, Xiao ML, Dong HL, Chen GD, Chen YM. Erythrocyte membrane n-3 polyunsaturated fatty acids are inversely associated with the presence and progression of nonalcoholic fatty liver disease in Chinese adults: a prospective study. Eur J Nutr 2019; 59:941-951. [PMID: 30937580 DOI: 10.1007/s00394-019-01953-2] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/27/2018] [Accepted: 03/20/2019] [Indexed: 01/22/2023]
Abstract
PURPOSE Previous studies have shown that high-dose supplementation with n-3 polyunsaturated fatty acids (PUFAs) may benefit patients with nonalcoholic fatty liver disease (NAFLD), but the association of n-3 PUFAs with NAFLD among individuals with normal diets is only speculative. We investigated the cross-sectional and prospective associations between n-3 PUFAs and NAFLD in Chinese adults. METHODS This community-based prospective study included 3049 men and women (40-75 years) in Guangzhou, China, whose participants completed an NAFLD ultrasound evaluation and erythrocyte PUFA tests. A total of 2660 participants underwent the second NAFLD evaluation approximately 3 years later. α-Linolenic acid (ALA), eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) in erythrocytes were measured by gas chromatography. RESULTS After adjusting for potential confounders, we observed inverse associations between DHA, DHA + EPA, total n-3 PUFAs and the presence of NAFLD in the cross-sectional analysis. The adjusted odds ratios (95% confidence interval) of NAFLD for the highest (vs. lowest) tertile were 0.74 (0.61, 0.90) for DHA, 0.82 (0.67, 1.00) for EPA, 0.73 (0.60, 0.88) for DHA + EPA and 0.74 (0.61, 0.91) for total n-3 PUFAs (all P values≤0.05). Over the average 3.12 years of follow-up, higher levels of DHA was associated with an improvement of NAFLD. The hazard ratio of improved NAFLD for the highest tertile was 1.18 (95% CI 1.09, 1.33) for DHA. Pathway analyses showed that favorable associations may be mediated by improvements in inflammatory markers (e.g., interleukin 1 beta and tumor necrosis factor alpha-like). CONCLUSIONS Erythrocyte membrane n-3 PUFAs are inversely associated with the presence and progression of NAFLD in Chinese adults. TRIAL REGISTRATIONS ClinicalTrials.gov NCT03179657.
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Affiliation(s)
- Zhan-Yong Chen
- Guangdong Provincial Key Laboratory of Food, Nutrition and Health, Department of Epidemiology, School of Public Health, Sun Yat-sen University, Guangzhou, 510080, China
- The First Affiliated Hospital, Sun Yat-sen University, 58 Zhongshan 2nd Road, Guangzhou, 510080, China
| | - Meng Liu
- Guangdong Provincial Key Laboratory of Food, Nutrition and Health, Department of Epidemiology, School of Public Health, Sun Yat-sen University, Guangzhou, 510080, China
| | - Li-Peng Jing
- Guangdong Provincial Key Laboratory of Food, Nutrition and Health, Department of Epidemiology, School of Public Health, Sun Yat-sen University, Guangzhou, 510080, China
| | - Mian-Li Xiao
- Guangdong Provincial Key Laboratory of Food, Nutrition and Health, Department of Epidemiology, School of Public Health, Sun Yat-sen University, Guangzhou, 510080, China
| | - Hong-Li Dong
- Guangdong Provincial Key Laboratory of Food, Nutrition and Health, Department of Epidemiology, School of Public Health, Sun Yat-sen University, Guangzhou, 510080, China
| | - Geng-Dong Chen
- Guangdong Provincial Key Laboratory of Food, Nutrition and Health, Department of Epidemiology, School of Public Health, Sun Yat-sen University, Guangzhou, 510080, China
| | - Yu-Ming Chen
- Guangdong Provincial Key Laboratory of Food, Nutrition and Health, Department of Epidemiology, School of Public Health, Sun Yat-sen University, Guangzhou, 510080, China.
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Perdomo CM, Frühbeck G, Escalada J. Impact of Nutritional Changes on Nonalcoholic Fatty Liver Disease. Nutrients 2019; 11:nu11030677. [PMID: 30901929 PMCID: PMC6470750 DOI: 10.3390/nu11030677] [Citation(s) in RCA: 133] [Impact Index Per Article: 22.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/28/2019] [Revised: 03/15/2019] [Accepted: 03/16/2019] [Indexed: 12/16/2022] Open
Abstract
Non-alcoholic fatty liver disease (NAFLD) is a major global health threat due to its growing incidence and prevalence. It is becoming the leading cause of liver disease in addition to its strong association with cardio-metabolic disease. Therefore, its prevention and treatment are of strong public interest. Therapeutic approaches emphasize lifestyle modifications including physical activity and the adoption of healthy eating habits that intend to mainly control body weight and cardio-metabolic risk factors associated with the metabolic syndrome. Lifestyle interventions may be reinforced by pharmacological treatment in advanced stages, though there is still no registered drug for the specific treatment of NAFLD. The purpose of this review is to assess the evidence available regarding the impact of dietary recommendations against NAFLD, highlighting the effect of macronutrient diet composition and dietary patterns in the management of NAFLD.
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Affiliation(s)
- Carolina M Perdomo
- Department of Endocrinology and Nutrition, Clínica Universidad de Navarra, 31008 Pamplona, Spain.
| | - Gema Frühbeck
- Department of Endocrinology and Nutrition, Clínica Universidad de Navarra, 31008 Pamplona, Spain.
- CIBER Fisiopatología de la Obesidad y Nutrición (CIBERobn), ISCIII, 28029 Madrid, Spain.
| | - Javier Escalada
- Department of Endocrinology and Nutrition, Clínica Universidad de Navarra, 31008 Pamplona, Spain.
- CIBER Fisiopatología de la Obesidad y Nutrición (CIBERobn), ISCIII, 28029 Madrid, Spain.
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Effect of Fish Oil Supplementation on Hepatic and Visceral Fat in Overweight Men: A Randomized Controlled Trial. Nutrients 2019; 11:nu11020475. [PMID: 30813440 PMCID: PMC6413081 DOI: 10.3390/nu11020475] [Citation(s) in RCA: 37] [Impact Index Per Article: 6.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/21/2018] [Revised: 02/12/2019] [Accepted: 02/20/2019] [Indexed: 12/16/2022] Open
Abstract
Being overweight increases the risk of the development of metabolic conditions such as non-alcoholic fatty liver disease (NAFLD), which is itself an independent predictor of cardiovascular disease. Omega-3 polyunsaturated fatty acid (PUFA) supplementation is recommended for prevention of chronic disease, and is thought to reduce raised liver fat, yet there have been few randomized controlled trials with accurate measurement of liver fat. We assessed the effect of 12 weeks of supplementation with omega-3 PUFA from fish oil versus placebo on quantified liver fat, liver tests, and body composition including visceral adipose tissue (VAT) in a double-blind randomized controlled trial. Fifty apparently healthy overweight men (BMI 25.0–29.9 kg/m2; waist > 94 cm) were randomly allocated to consume fish oil (total daily dose: 1728 mg marine triglycerides, of which 588 mg EPA and 412 mg DHA, combined with 200 mg antioxidant, coenzyme Q10) or placebo (olive oil capsules) daily for 12 weeks. Liver fat was assessed using proton magnetic resonance spectroscopy. All outcomes were assessed at baseline and following 6 and 12 weeks of supplementation. Baseline liver fat was 4.6 ± 0.5% (range: 0.6 to 18.2%); 16 (32%) participants met the criteria for NAFLD (>5.5% liver fat). Repeated measures ANOVA revealed no significant time or group × time effect for fish oil versus placebo for liver fat, liver enzymes, anthropometry, or body composition including VAT (p > 0.05 for all), with similar finding for sub-analysis of participants with NAFLD. Omega-3 PUFA did not appear to be an effective agent for reducing liver fat in overweight men. The factors determining the health benefits of omega-3 PUFA supplementation on an individual level need to be clarified.
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