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Malik A, Javaid S, Malik MI, Qureshi S. Relationship between sarcopenia and metabolic dysfunction-associated steatotic liver disease (MASLD): A systematic review and meta-analysis. Ann Hepatol 2024; 29:101544. [PMID: 39214253 DOI: 10.1016/j.aohep.2024.101544] [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: 10/25/2023] [Revised: 05/13/2024] [Accepted: 06/17/2024] [Indexed: 09/04/2024]
Abstract
INTRODUCTION AND OBJECTIVES Metabolic dysfunction-associated steatotic liver disease (MASLD) formerly known as Nonalcoholic fatty liver disease (NAFLD) is a common chronic disease. Identifying MASLD risk factors could help early intervention and reduce the burden of the disease. Previous studies investigated the association between sarcopenia and NAFLD. Several trials were published after the last meta-analysis with indecisive results. This is an updated meta-analysis which aims to assess the association between sarcopenia, MASLD, and MASLD-related fibrosis. MATERIALS AND METHODS Relevant trials published on PubMed, Web of Science, Scopus, and Cochrane Library databases until October 2022 were included. We included studies in which skeletal mass index (SMI) or sarcopenia was compared between patients with and without NAFLD now MASLD. Also, studies comparing fibrosis between MASLD patients with and without sarcopenia were included. Data were pooled as odds ratios (ORs) and 95 % confidence intervals (CIs) using Review Manager Software. RESULTS A total of 25 studies were included. The incidence of sarcopenia was significantly higher in MASLD than controls (OR, 1.25; 95 % CI, 1.08-1.44; P = 0.003). SMI odds showed no significant difference between MASLD patients and controls (OR, 1.02; 95 % CI, 0.91-1.15; P = 0.7). MASLD patients with sarcopenia had higher odds of fibrosis than MASLD patients without sarcopenia (OR, 1.49; 95 % CI, 1.03-2.14; P = 0.03). CONCLUSIONS Sarcopenia increased MASLD's probability and was associated with a higher probability of liver fibrosis in MASLD patients. However, SMI had no predictive value of MASLD occurrence.
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Affiliation(s)
- Adnan Malik
- Mountain Vista Medical Center, Mesa Arizona, USA.
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Almohawes ZN, El-Kott A, Morsy K, Shati AA, El-Kenawy AE, Khalifa HS, Elsaid FG, Abd-Lateif AEKM, Abu-Zaiton A, Ebealy ER, Abdel-Daim MM, Ghanem RA, Abd-Ella EM. Salidroside inhibits insulin resistance and hepatic steatosis by downregulating miR-21 and subsequent activation of AMPK and upregulation of PPARα in the liver and muscles of high fat diet-fed rats. Arch Physiol Biochem 2024; 130:257-274. [PMID: 35061559 DOI: 10.1080/13813455.2021.2024578] [Citation(s) in RCA: 4] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/15/2021] [Revised: 12/15/2021] [Accepted: 12/27/2021] [Indexed: 02/06/2023]
Abstract
This study evaluated if salidroside (SAL) alleviates high-fat diet (HFD)-induced non-alcoholic fatty liver disease (NAFLD) by downregulating miR-21. Rats (n = 8/group) were treated for 12 weeks as normal diet (control/ND), ND + agmoir negative control (NC) (150 µg/kg), ND + SAL (300 mg/kg), HFD, HFD + SAL, HFD + compound C (an AMPK inhibitor) (200 ng/kg), HFD + SAL + NXT629 (a PPAR-α antagonist) (30 mg/kg), and HFD + SAL + miR-21 agomir (150 µg/kg). SAL improved glucose and insulin tolerance and preserved livers in HFD-fed rats. In ND and HFD-fed rats, SAL reduced levels of serum and hepatic lipids and the hepatic expression of SREBP1, SREBP2, fatty acid (FA) synthase, and HMGCOAR. It also activated hepatic Nrf2 and increased hepatic/muscular activity of AMPK and levels of PPARα. All effects afforded by SAL were prevented by CC, NXT629, and miR-21 agmoir. In conclusion, activation of AMPK and upregulation of PPARα mediate the anti-steatotic effect of SAL.
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Affiliation(s)
- Zakiah N Almohawes
- Biology Department, College of Science, Princess Nourah Bint Abdulrahman University, Riyadh, Saudi Arabia
| | - Attalla El-Kott
- Biology Department, College of Science, King Khalid University, Abha, Saudi Arabia
- Zoology Department, College of Science, Damanhour University, Damanhour, Egypt
| | - Kareem Morsy
- Biology Department, College of Science, King Khalid University, Abha, Saudi Arabia
- Zoology Department, College of Science, Cairo University, Cairo, Egypt
| | - Ali A Shati
- Biology Department, College of Science, King Khalid University, Abha, Saudi Arabia
| | - Ayman E El-Kenawy
- Pathology Department, College of Medicine, Taif University, Taif, Saudi Arabia
| | - Heba S Khalifa
- Zoology Department, College of Science, Damanhour University, Damanhour, Egypt
| | - Fahmy G Elsaid
- Biology Department, College of Science, King Khalid University, Abha, Saudi Arabia
- Zoology Department, Faculty of Science, Mansoura University, Mansoura, Egypt
| | | | | | - Eman R Ebealy
- Biology Department, College of Science, King Khalid University, Abha, Saudi Arabia
| | - Mohamed M Abdel-Daim
- Pharmaceutical Sciences Department, Pharmacy Program, Batterjee Medical College, Jeddah, Saudi Arabia
- Pharmacology Department, Faculty of Veterinary Medicine, Suez Canal University, Ismailia, Egypt
| | - Reham A Ghanem
- Oral Biology Department, Faculty of Oral and Dental Medicine, Delta University for Science and Technology, Gamasa, Egypt
| | - Eman M Abd-Ella
- Zoology Department, College of Science, Fayoum University, Fayoum, Egypt
- Biology Department, College of Science and Art, Al-Baha University, Al-Mandaq, Saudi Arabia
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Nendouvhada LP, Sibuyi NRS, Fadaka AO, Meyer S, Madiehe AM, Meyer M, Gabuza KB. Phytonanotherapy for the Treatment of Metabolic Dysfunction-Associated Steatotic Liver Disease. Int J Mol Sci 2024; 25:5571. [PMID: 38891759 PMCID: PMC11171778 DOI: 10.3390/ijms25115571] [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] [Received: 04/20/2024] [Revised: 04/27/2024] [Accepted: 04/27/2024] [Indexed: 06/21/2024] Open
Abstract
Metabolic dysfunction-associated steatotic liver disease (MASLD), previously known as nonalcoholic fatty liver disease, is a steatotic liver disease associated with metabolic syndrome (MetS), especially obesity, hypertension, diabetes, hyperlipidemia, and hypertriglyceridemia. MASLD in 43-44% of patients can progress to metabolic dysfunction-associated steatohepatitis (MASH), and 7-30% of these cases will progress to liver scarring (cirrhosis). To date, the mechanism of MASLD and its progression is not completely understood and there were no therapeutic strategies specifically tailored for MASLD/MASH until March 2024. The conventional antiobesity and antidiabetic pharmacological approaches used to reduce the progression of MASLD demonstrated favorable peripheral outcomes but insignificant effects on liver histology. Alternatively, phyto-synthesized metal-based nanoparticles (MNPs) are now being explored in the treatment of various liver diseases due to their unique bioactivities and reduced bystander effects. Although phytonanotherapy has not been explored in the clinical treatment of MASLD/MASH, MNPs such as gold NPs (AuNPs) and silver NPs (AgNPs) have been reported to improve metabolic processes by reducing blood glucose levels, body fat, and inflammation. Therefore, these actions suggest that MNPs can potentially be used in the treatment of MASLD/MASH and related metabolic diseases. Further studies are warranted to investigate the feasibility and efficacy of phytonanomedicine before clinical application.
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Affiliation(s)
- Livhuwani P. Nendouvhada
- Department of Science and Innovation/Mintek Nanotechnology Innovation Centre, Biolabels Research Node, Department of Biotechnology, University of the Western Cape, Bellville 7535, South Africa (A.O.F.); (M.M.)
- Biomedical Research and Innovation Platform, South African Medical Research Council, Tygerberg 7505, South Africa
| | - Nicole R. S. Sibuyi
- Department of Science and Innovation/Mintek Nanotechnology Innovation Centre, Biolabels Research Node, Department of Biotechnology, University of the Western Cape, Bellville 7535, South Africa (A.O.F.); (M.M.)
- Health Platform, Advanced Materials Division, Mintek, Randburg 2194, South Africa
| | - Adewale O. Fadaka
- Department of Science and Innovation/Mintek Nanotechnology Innovation Centre, Biolabels Research Node, Department of Biotechnology, University of the Western Cape, Bellville 7535, South Africa (A.O.F.); (M.M.)
| | - Samantha Meyer
- Department of Biomedical Sciences, Faculty of Health and Wellness Sciences, Cape Peninsula University of Technology, Bellville 7535, South Africa;
| | - Abram M. Madiehe
- Department of Science and Innovation/Mintek Nanotechnology Innovation Centre, Biolabels Research Node, Department of Biotechnology, University of the Western Cape, Bellville 7535, South Africa (A.O.F.); (M.M.)
| | - Mervin Meyer
- Department of Science and Innovation/Mintek Nanotechnology Innovation Centre, Biolabels Research Node, Department of Biotechnology, University of the Western Cape, Bellville 7535, South Africa (A.O.F.); (M.M.)
| | - Kwazikwakhe B. Gabuza
- Department of Science and Innovation/Mintek Nanotechnology Innovation Centre, Biolabels Research Node, Department of Biotechnology, University of the Western Cape, Bellville 7535, South Africa (A.O.F.); (M.M.)
- Biomedical Research and Innovation Platform, South African Medical Research Council, Tygerberg 7505, South Africa
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Kongmalai T, Srinonprasert V, Anothaisintawee T, Kongmalai P, McKay G, Attia J, Thakkinstian A. New anti-diabetic agents for the treatment of non-alcoholic fatty liver disease: a systematic review and network meta-analysis of randomized controlled trials. Front Endocrinol (Lausanne) 2023; 14:1182037. [PMID: 37441498 PMCID: PMC10335801 DOI: 10.3389/fendo.2023.1182037] [Citation(s) in RCA: 15] [Impact Index Per Article: 7.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/08/2023] [Accepted: 04/14/2023] [Indexed: 07/15/2023] Open
Abstract
Objectives This network meta-analysis aims to compare the efficacy and safety of new anti-diabetic medications for the treatment of non-alcoholic fatty liver disease (NAFLD). Materials and methods PubMed and Scopus were searched from inception to 27th March 2022 to identify all randomized controlled trials (RCTs) in NAFLD patients. Outcomes included reductions in intrahepatic steatosis (IHS) and liver enzyme levels. The efficacy and safety of DPP-4 inhibitors, GLP-1 agonists, SGLT-2 inhibitors, and other therapies were indirectly compared using a NMA approach. Unstandardized mean difference (USMD) with 95% confidence intervals (CI) were calculated. Results 2,252 patients from 31 RCTs were included. "Add-on" GLP-1 agonists with standard of care (SoC) treatment showed significantly reduced IHS compared to SoC alone [USMD (95%CI) -3.93% (-6.54%, -1.33%)]. Surface under the cumulative ranking curve (SUCRA) identified GLP-1 receptor agonists with the highest probability to reduce IHS (SUCRA 88.5%), followed by DPP-4 inhibitors (SUCRA 69.6%) and pioglitazone (SUCRA 62.2%). "Add-on" GLP-1 receptor agonists were also the most effective treatment for reducing liver enzyme levels; AST [USMD of -5.04 (-8.46, -1.62)], ALT [USMD of -9.84 (-16.84, -2.85)] and GGT [USMD of -15.53 (-22.09, -8.97)] compared to SoC alone. However, GLP-1 agonists were most likely to be associated with an adverse event compared to other interventions. Conclusion GLP-1 agonists may represent the most promising anti-diabetic treatment to reduce hepatic steatosis and liver enzyme activity in T2DM and NAFLD patients. Nevertheless, longer-term studies are required to determine whether this delays progression of liver cirrhosis in patients with NAFLD and T2DM. Systematic review registration https://www.crd.york.ac.uk/prospero/, identifier CRD42021259336.1.
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Affiliation(s)
- Tanawan Kongmalai
- Division of Endocrinology and Metabolism, Department of Medicine, Faculty of Medicine, Siriraj Hospital, Mahidol University, Bangkok, Thailand
| | - Varalak Srinonprasert
- Siriraj Health Policy Unit, Faculty of Medicine, Siriraj Hospital, Mahidol University, Bangkok, Thailand
- Division of Geriatric Medicine, Department of Medicine, Faculty of Medicine, Siriraj Hospital, Mahidol University, Bangkok, Thailand
- Mahidol University Health Technology Assessment Graduate Program, Mahidol University, Bangkok, Thailand
| | - Thunyarat Anothaisintawee
- Department of Clinical Epidemiology and Biostatistics, Faculty of Medicine, Ramathibodi Hospital, Mahidol University, Bangkok, Thailand
| | - Pinkawas Kongmalai
- Department of Orthopaedics, Faculty of Medicine, Srinakharinwirot University, Ongkharak, Nakhon Nayok, Thailand
| | - Gareth McKay
- Centre for Public Health, School of Medicine, Dentistry, and Biomedical Sciences, Queen’s University, Belfast, Ireland
| | - John Attia
- School of Medicine and Public Health, University of Newcastle, Callaghan, NSW, Australia
| | - Ammarin Thakkinstian
- Mahidol University Health Technology Assessment Graduate Program, Mahidol University, Bangkok, Thailand
- Department of Clinical Epidemiology and Biostatistics, Faculty of Medicine, Ramathibodi Hospital, Mahidol University, Bangkok, Thailand
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Ding Y, Tang Z, Wang M, Wang M, Zhang R, Zhang L, Zhang M, Guan Q, Wang J. Combining serum uric acid and fatty liver index to improve prediction quality of nonalcoholic fatty liver disease. Saudi J Gastroenterol 2023:371209. [PMID: 36876619 DOI: 10.4103/sjg.sjg_484_22] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 03/07/2023] Open
Abstract
Background The significant association between serum uric acid (SUA) and nonalcoholic fatty liver disease (NAFLD) is well documented. In this report, we tested the hypothesis that SUA might improve the widely studied fatty liver index (FLI) to predict NAFLD. Methods A cross-sectional study was performed in a community of Nanjing, China. The population data on sociodemographics, physical examinations, and biochemical tests were collected from July to September 2018. The associations of SUA and FLI with NAFLD were analyzed using linear correlation, multiple linear regressions, binary logistic analyses, and area under receiver-operating characteristic curve (AUROC). Results A total of 3,499 people were included in this study, of which 36.9% had NAFLD. The prevalence of NAFLD increased with the increase of SUA levels (all P <.05). Logistic regression analyses revealed that SUA was significantly associated with an increased risk of NAFLD (all P <.001). The NAFLD predictive value after combining SUA with FLI was superior to FLI, especially in females (AUROCSUA + FLI = 0.911 vs. AUROCFLI = 0.903, P <.05). The reclassification of NAFLD also significantly improved, based on net reclassification improvement (0.053, 95% confidence interval [CI]: 0.022-0.085, P <.001) and integrated discrimination improvement (0.096, 95% CI: 0.090-0.102, P <.001). A regression formula of this combined algorithm was proposed as: The novel formula = 0.032* waist circumference + 0.303* body mass index + 1.301* natural logarithm of triglyceride + 0.478* natural logarithm of glutamyl transpeptidase + 0.002* SUA- 18.823. At the cutoff value of 13.3, the sensitivity and specificity of this model were 89.2% and 78.4%, respectively. Conclusions SUA level was positively associated with NAFLD prevalence. A new formula combining SUA with FLI may serve as a better indicator to predict NAFLD compared to FLI, especially in females.
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Affiliation(s)
- Yajie Ding
- Department of Fundamental and Community Nursing, School of Nursing, Nanjing Medical University, Nanjing, China
| | - Zongzhe Tang
- Department of Fundamental and Community Nursing, School of Nursing, Nanjing Medical University, Nanjing, China
| | - Minxian Wang
- Hospital Development Management Office, Nanjing Medical University, Nanjing, China
| | - Min Wang
- Department of Fundamental and Community Nursing, School of Nursing, Nanjing Medical University, Nanjing, China
| | - Ru Zhang
- Department of Fundamental and Community Nursing, School of Nursing, Nanjing Medical University, Nanjing, China
| | - Liuxin Zhang
- The Nethersole School of Nursing, Faculty of Medicine, The Chinese University of Hong Kong, Sha Tin, New Territories, Hong Kong (SAR), China
| | - Mengting Zhang
- Department of Fundamental and Community Nursing, School of Nursing, Nanjing Medical University, Nanjing, China
| | - Qing Guan
- Department of Fundamental and Community Nursing, School of Nursing, Nanjing Medical University, Nanjing, China
| | - Jie Wang
- Department of Fundamental and Community Nursing, School of Nursing, Nanjing Medical University, Nanjing, China
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Cernea S, Onișor D. Screening and interventions to prevent nonalcoholic fatty liver disease/nonalcoholic steatohepatitis-associated hepatocellular carcinoma. World J Gastroenterol 2023; 29:286-309. [PMID: 36687124 PMCID: PMC9846941 DOI: 10.3748/wjg.v29.i2.286] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/18/2022] [Revised: 11/06/2022] [Accepted: 12/21/2022] [Indexed: 01/06/2023] Open
Abstract
Liver cancer is the sixth most commonly diagnosed cancer worldwide, with hepatocellular carcinoma (HCC) comprising most cases. Besides hepatitis B and C viral infections, heavy alcohol use, and nonalcoholic steatohepatitis (NASH)-associated advanced fibrosis/cirrhosis, several other risk factors for HCC have been identified (i.e. old age, obesity, insulin resistance, type 2 diabetes). These might in fact partially explain the occurrence of HCC in non-cirrhotic patients without viral infection. HCC surveillance through effective screening programs is still an unmet need for many nonalcoholic fatty liver disease (NAFLD) patients, and identification of pre-cirrhotic individuals who progress to HCC represents a substantial challenge in clinical practice at the moment. Patients with NASH-cirrhosis should undergo systematic HCC surveillance, while this might be considered in patients with advanced fibrosis based on individual risk assessment. In this context, interventions that potentially prevent NAFLD/ NASH-associated HCC are needed. This paper provided an overview of evidence related to lifestyle changes (i.e. weight loss, physical exercise, adherence to healthy dietary patterns, intake of certain dietary components, etc.) and pharmacological interventions that might play a protective role by targeting the underlying causative factors and pathogenetic mechanisms. However, well-designed prospective studies specifically dedicated to NAFLD/NASH patients are still needed to clarify the relationship with HCC risk.
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Affiliation(s)
- Simona Cernea
- Department M3/Internal Medicine I, George Emil Palade University of Medicine, Pharmacy, Science and Technology of Târgu Mureș, Târgu Mureş 540139, Romania
- Diabetes, Nutrition and Metabolic Diseases Outpatient Unit, Emergency County Clinical Hospital, Târgu Mureş 540136, Romania
| | - Danusia Onișor
- Department ME2/Internal Medicine VII, George Emil Palade University of Medicine, Pharmacy, Science, and Technology of Târgu Mureş, Târgu Mureş 540139, Romania
- Gastroenterology Department, Mureș County Clinical Hospital, Târgu Mureș 540072, Romania
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Gillessen A, Angelico F, Chen J, Lu L, Lucena MI, Fu Q, Xie Q, Andrade RJ, Xie W, Xu X, Yu Y, Mao YM, Nan Y. Silymarin for Treating Toxic Liver Disease: International Consensus Recommendations. GASTRO HEP ADVANCES 2022; 1:882-893. [PMID: 39131840 PMCID: PMC11307908 DOI: 10.1016/j.gastha.2022.05.006] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 01/24/2022] [Accepted: 05/09/2022] [Indexed: 08/13/2024]
Abstract
Chronic liver disease (CLD) is a leading health problem impacting the quality of life globally. China shares a major global burden of CLD-including alcoholic liver disease, nonalcoholic fatty liver disease/metabolic dysfunction-associated fatty liver disease, and drug-induced liver injury, except for chronic viral hepatitis. Several exogenous toxins or endogenous metabolic insults trigger hepatic pathology toward steatosis, inflammation, and fibrosis, which, if left untreated, may culminate in liver cirrhosis. Oxidative stress is a common pathomechanism underlying all phenotypes of toxic liver injury; thus, these may be brought under a unified entity, viz. toxic liver disease (TLD). Therefore, a common strategy to treat TLD is to use antioxidants as hepatoprotective agents. The cornerstone for treating fatty liver disease is lifestyle modification, diet, exercise, and behavioral therapy, along with the limited use of pharmacological agents. Available preclinical and clinical evidence indicates that silymarin is a hepatoprotective agent with established antioxidant, anti-inflammatory, antifibrotic effects. An international expert panel of clinicians was convened to discuss combining alcoholic liver disease, nonalcoholic fatty liver disease/metabolic dysfunction-associated fatty liver disease, drug-induced liver injury, and liver cirrhosis under the single definition of TLD, based on the shared pathologic mechanism of oxidative stress. The panel highlighted the significance of silymarin as an antioxidant treatment for TLD.
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Affiliation(s)
- Anton Gillessen
- Department of Internal Medicine, Herz-Jesu-Hospital, Muenster, Germany
| | - Francesco Angelico
- Department of Public Health and Infectious Diseases, Sapienza University School of Medicine, Rome, Italy
| | - Jun Chen
- Department of Liver Disease Medical Center/Head of the Fourth Department of Liver Disease, Shenzhen Third People's Hospital, Shenzhen, China
| | - Lungen Lu
- Department of Gastroenterology, Shanghai General Hospital, Shanghai, China
| | - Maria Isabel Lucena
- Department of Pharmacology, School of Medicine, University of Málaga, Málaga, Spain
| | - Qingchun Fu
- Department of Liver Disease, Centre of Shanghai Public Health Clinical Centre, Shanghai, China
| | - Qing Xie
- Department of Infectious Diseases, Ruijin Hospital, Shanghai, China
| | - Raul J. Andrade
- Services of Gastroenterology & Clinical Pharmacology, Málaga Biomedical Research Institute, IBIMA, University Hospital, University of Málaga, Málaga, Spain
| | - Wen Xie
- Liver Disease Centre, Beijing Ditan Hospital Capital Medical University, Beijing, China
| | - Xiaoyuan Xu
- Department of Infectious Diseases, Peking University Health Science Centre, Beijing, China
| | - Yanyan Yu
- Department of Infectious Disease, Peking University First Hospital, Beijing, China
| | - Yi-min Mao
- Department of Gastroenterology, Renji Hospital, Shanghai, China
| | - Yuemin Nan
- Department of Liver Diseases, The Third Hospital of Hebei Medical University, Shijiazhuang, China
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Hong W, Zhang T, Yan J, Yu J, He B, Wu L, Yao K, Mao W, Chen Z. Bioinformatics analysis of an animal model of diet-induced nonalcoholic fatty liver disease with rapid progression. Exp Biol Med (Maywood) 2021; 247:263-275. [PMID: 34775841 DOI: 10.1177/15353702211055099] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/27/2022] Open
Abstract
Nonalcoholic fatty liver disease (NAFLD) develops rapidly in high-fat diet (HFD) fed Mongolian gerbil (Meriones unguiculatus). Here, we aim to explore the gene expression characteristics of Mongolian gerbil to better understand the underlying mechanism in this animal model. Mongolian gerbils were fed with normal diet or HFD for different periods. High-throughput sequencing was carried out on the hepatic mRNA and bioinformatics analysis was further performed. Eight hub genes Cd44, App, Cdc42, Cd68, Cxcr4, Csf1r, Adgre1, and Fermt3, which were involved in inflammation, fibrosis, and HCC were obtained. Four significant independent poor prognostic factors for HCC (GPC1, ARPC1B, DAB2, and CFL1) were screened out. qRT-PCR result showed that the above genes expressed high levels in different periods of modeling process. The findings of this study provide useful information for further studies on Mongolian gerbil NAFLD model.
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Affiliation(s)
- Wei Hong
- The Second Central Laboratory, the First Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou 310016, China.,Key Laboratory of Integrative Chinese and Western Medicine for the Diagnosis and Treatment of Circulatory Diseases of Zhejiang Province, Hangzhou 310016, China
| | - Tingting Zhang
- The Second Central Laboratory, the First Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou 310016, China.,Key Laboratory of Integrative Chinese and Western Medicine for the Diagnosis and Treatment of Circulatory Diseases of Zhejiang Province, Hangzhou 310016, China
| | - Junbin Yan
- The Second Central Laboratory, the First Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou 310016, China.,Key Laboratory of Integrative Chinese and Western Medicine for the Diagnosis and Treatment of Circulatory Diseases of Zhejiang Province, Hangzhou 310016, China
| | - Jianshun Yu
- The Second Central Laboratory, the First Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou 310016, China
| | - Beihui He
- The Second Central Laboratory, the First Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou 310016, China.,Key Laboratory of Integrative Chinese and Western Medicine for the Diagnosis and Treatment of Circulatory Diseases of Zhejiang Province, Hangzhou 310016, China
| | - Liyan Wu
- The Second Central Laboratory, the First Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou 310016, China
| | - Kannan Yao
- The Second Central Laboratory, the First Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou 310016, China.,Key Laboratory of Integrative Chinese and Western Medicine for the Diagnosis and Treatment of Circulatory Diseases of Zhejiang Province, Hangzhou 310016, China
| | - Wei Mao
- Key Laboratory of Integrative Chinese and Western Medicine for the Diagnosis and Treatment of Circulatory Diseases of Zhejiang Province, Hangzhou 310016, China.,Department of Cardiology, the First Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou 310016, China
| | - Zhiyun Chen
- The Second Central Laboratory, the First Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou 310016, China.,Key Laboratory of Integrative Chinese and Western Medicine for the Diagnosis and Treatment of Circulatory Diseases of Zhejiang Province, Hangzhou 310016, China
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Wiśniewska A, Stachowicz A, Kuś K, Ulatowska-Białas M, Totoń-Żurańska J, Kiepura A, Stachyra K, Suski M, Gajda M, Jawień J, Olszanecki R. Inhibition of Atherosclerosis and Liver Steatosis by Agmatine in Western Diet-Fed apoE-Knockout Mice Is Associated with Decrease in Hepatic De Novo Lipogenesis and Reduction in Plasma Triglyceride/High-Density Lipoprotein Cholesterol Ratio. Int J Mol Sci 2021; 22:ijms221910688. [PMID: 34639029 PMCID: PMC8509476 DOI: 10.3390/ijms221910688] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/31/2021] [Revised: 09/26/2021] [Accepted: 09/28/2021] [Indexed: 12/15/2022] Open
Abstract
Atherosclerosis and NAFLD are the leading causes of death worldwide. The hallmark of NAFLD is triglyceride accumulation caused by an imbalance between lipogenesis de novo and fatty acid oxidation. Agmatine, an endogenous metabolite of arginine, exerts a protective effect on mitochondria and can modulate fatty acid metabolism. In the present study, we investigate the influence of agmatine on the progression of atherosclerotic lesions and the development of hepatic steatosis in apoE−/− mice fed with a Western high-fat diet, with a particular focus on its effects on the DNL pathway in the liver. We have proved that treatment of agmatine inhibits the progression of atherosclerosis and attenuates hepatic steatosis in apoE−/− mice on a Western diet. Such effects are associated with decreased total macrophage content in atherosclerotic plaque as well as a decrease in the TG levels and the TG/HDL ratio in plasma. Agmatine also reduced TG accumulation in the liver and decreased the expression of hepatic genes and proteins involved in lipogenesis de novo such as SREBP-1c, FASN and SCD1. In conclusion, agmatine may present therapeutic potential for the treatment of atherosclerosis and fatty liver disease. However, an exact understanding of the mechanisms of the advantageous actions of agmatine requires further study.
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Affiliation(s)
- Anna Wiśniewska
- Chair of Pharmacology, Faculty of Medicine, Jagiellonian University Medical College, 31-531 Cracow, Poland; (A.W.); (A.S.); (K.K.); (J.T.-Ż.); (A.K.); (K.S.); (M.S.); (J.J.)
| | - Aneta Stachowicz
- Chair of Pharmacology, Faculty of Medicine, Jagiellonian University Medical College, 31-531 Cracow, Poland; (A.W.); (A.S.); (K.K.); (J.T.-Ż.); (A.K.); (K.S.); (M.S.); (J.J.)
| | - Katarzyna Kuś
- Chair of Pharmacology, Faculty of Medicine, Jagiellonian University Medical College, 31-531 Cracow, Poland; (A.W.); (A.S.); (K.K.); (J.T.-Ż.); (A.K.); (K.S.); (M.S.); (J.J.)
| | | | - Justyna Totoń-Żurańska
- Chair of Pharmacology, Faculty of Medicine, Jagiellonian University Medical College, 31-531 Cracow, Poland; (A.W.); (A.S.); (K.K.); (J.T.-Ż.); (A.K.); (K.S.); (M.S.); (J.J.)
| | - Anna Kiepura
- Chair of Pharmacology, Faculty of Medicine, Jagiellonian University Medical College, 31-531 Cracow, Poland; (A.W.); (A.S.); (K.K.); (J.T.-Ż.); (A.K.); (K.S.); (M.S.); (J.J.)
| | - Kamila Stachyra
- Chair of Pharmacology, Faculty of Medicine, Jagiellonian University Medical College, 31-531 Cracow, Poland; (A.W.); (A.S.); (K.K.); (J.T.-Ż.); (A.K.); (K.S.); (M.S.); (J.J.)
| | - Maciej Suski
- Chair of Pharmacology, Faculty of Medicine, Jagiellonian University Medical College, 31-531 Cracow, Poland; (A.W.); (A.S.); (K.K.); (J.T.-Ż.); (A.K.); (K.S.); (M.S.); (J.J.)
| | - Mariusz Gajda
- Department of Histology, Jagiellonian University Medical College, 31-034 Cracow, Poland;
| | - Jacek Jawień
- Chair of Pharmacology, Faculty of Medicine, Jagiellonian University Medical College, 31-531 Cracow, Poland; (A.W.); (A.S.); (K.K.); (J.T.-Ż.); (A.K.); (K.S.); (M.S.); (J.J.)
| | - Rafał Olszanecki
- Chair of Pharmacology, Faculty of Medicine, Jagiellonian University Medical College, 31-531 Cracow, Poland; (A.W.); (A.S.); (K.K.); (J.T.-Ż.); (A.K.); (K.S.); (M.S.); (J.J.)
- Correspondence: ; Tel.: +48-12-421-1168
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Sewter R, Heaney S, Patterson A. Coffee Consumption and the Progression of NAFLD: A Systematic Review. Nutrients 2021; 13:2381. [PMID: 34371891 PMCID: PMC8308484 DOI: 10.3390/nu13072381] [Citation(s) in RCA: 14] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/02/2021] [Revised: 07/01/2021] [Accepted: 07/06/2021] [Indexed: 11/23/2022] Open
Abstract
Non-alcoholic fatty liver disease (NAFLD) is the leading cause of chronic liver disease in developed countries. Coffee is one of the most consumed beverages in the world and has been shown to be beneficial in limiting progression in chronic liver disease in general. However, research surrounding the impact of coffee consumption on NAFLD progression is limited. This systematic review aimed to investigate the relationship between coffee consumption and the progression of liver disease, specifically for cases of NAFLD. MEDLINE, EMBASE, CINAHL, the Cochrane Library, and Scopus were searched for published studies that evaluated the effects of coffee consumption on the progression of NAFLD. The results are presented in a narrative synthesis with principal summary measures, including odds ratios, p-values, and differences in mean coffee intake in relation to severity of NAFLD. Five studies met the inclusion criteria and were included in this review. There was no trial evidence among NAFLD patients, rather all studies were of a cross-sectional design. Using the Academy of Nutrition and Dietetics Quality Criteria Checklist, four studies received a positive rating, with the remaining study receiving a neutral rating. Overall, four out of the five studies reported a statistically significant relationship between coffee consumption and the severity of fibrosis. Methods around capturing and defining coffee consumption were heterogeneous and therefore an effective dose could not be elucidated. Results suggest that higher coffee consumption is inversely associated with the severity of hepatic fibrosis in individuals with NAFLD. However, further research is required to elucidate the optimum quantity and form/preparation of coffee required to exert this hepatoprotective role.
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Affiliation(s)
- Rebecca Sewter
- School of Health Sciences, College of Health, Medicine and Wellbeing, University of Newcastle, Callaghan, NSW 2308, Australia; (R.S.); (S.H.)
| | - Susan Heaney
- School of Health Sciences, College of Health, Medicine and Wellbeing, University of Newcastle, Callaghan, NSW 2308, Australia; (R.S.); (S.H.)
- Department of Rural Health, College of Health, Medicine and Wellbeing, University of Newcastle, Port Macquarie, NSW 2444, Australia
| | - Amanda Patterson
- School of Health Sciences, College of Health, Medicine and Wellbeing, University of Newcastle, Callaghan, NSW 2308, Australia; (R.S.); (S.H.)
- Priority Research Centre for Physical Activity and Nutrition, University of Newcastle, Callaghan, NSW 2308, Australia
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11
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Teshome G, Ambachew S, Fasil A, Abebe M. Efficacy of Glucagon-Like Peptide-1 Analogs in Nonalcoholic Fatty Liver Disease: A Systematic Review. Hepat Med 2020; 12:139-151. [PMID: 33061687 PMCID: PMC7522518 DOI: 10.2147/hmer.s265631] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/11/2020] [Accepted: 09/01/2020] [Indexed: 12/13/2022] Open
Abstract
Background Nonalcoholic fatty liver disease (NAFLD) is the most common chronic liver disease. It is believed to be the hepatic manifestation of the metabolic syndrome. Many treatment approaches have been suggested so far, and several types of studies have been done to find treatment for NAFLD, the most promising of which are those with lifestyle interventions. Objective The aim of this systematic review was to evaluate the efficacy and safety of glucagon-like peptide-1 (GLP-1) analogs on the management of NAFLD. Methods The PubMed, MEDLINE, and Cochrane Central Library were searched to identify randomized controlled trials, single arm trials, and cohorts that compared GLP-1 analogs with a control treatment or baseline values with respect to efficacy and safety in patients living with NAFLD. The key outcomes were a change in serum transaminase, resolution of disease status measured by imaging or histological techniques, improvement in insulin resistance, and reduction in body weight. Results Initial searching retrieved 201 peer-reviewed articles and abstracts. Ten studies met all inclusion criteria. The review included a total of 590 participants with NAFLD. Following administration of GLP-1 analogs, a decrease in serum transaminases, improvement in liver histology and insulin resistance, and a reduction in body weight were observed. Compared with baseline, body weight, alanine aminotransferase, aspartate aminotransferase, and gamma glutamyltransferase were decreased by 5.5%, 59.5%, 52.8%, and 44.8%, respectively, due to GLP-1. Likewise, a reduction of proinflammatory cytokines and fibrosis markers and an enhancement of protective adipokines were observed in some of the studies. Conclusion The decrease in a key biochemical marker of liver injury following treatment with GLP-1 analogs, as well as improvements in imaging and histology, suggests that these agents may be effective alternatives for managing NAFLD. Registration CRD42018087262.
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Affiliation(s)
- Getnet Teshome
- University of Gondar Comprehensive Specialized Hospital, University of Gondar, Gondar, Amhara, Ethiopia
| | - Sintayehu Ambachew
- Department of Clinical Chemistry, University of Gondar, Gondar, Amhara, Ethiopia
| | - Alebachew Fasil
- Department of Clinical Chemistry, University of Gondar, Gondar, Amhara, Ethiopia
| | - Molla Abebe
- Department of Clinical Chemistry, University of Gondar, Gondar, Amhara, Ethiopia
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12
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Cernea S, Cahn A, Raz I. Pharmacological management of nonalcoholic fatty liver disease in type 2 diabetes. Expert Rev Clin Pharmacol 2017; 10:535-547. [PMID: 28276774 DOI: 10.1080/17512433.2017.1300059] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
INTRODUCTION The prevalence of nonalcoholic fatty liver disease (NAFLD) in patients with type 2 diabetes (T2D) is high and it is associated with poor prognosis. Hepatic steatosis results as a consequence of excessive hepatic lipid accumulation which correlates with insulin resistance and lipotoxicity, with subsequent oxidative stress, inflammation, apoptosis and fibrosis. Areas covered: This article presents the main pathophysiologic mechanisms and currently available drugs evaluated for their therapeutic effects on NAFLD/nonalcoholic steatohepatitis (NASH) and drugs under development that target relevant pathogenetic pathways. However, to date there is no particular drug approved for treatment of NAFLD in patients with T2D. Expert commentary: Early recognition and intervention are essential to ameliorate disease progression. Specific recommendations are still needed for NAFLD/NASH screening and diagnosis and therapeutic algorithm in patients with T2D. Lifestyle optimization with significant weight loss is a key intervention in patients with NAFLD and T2D. Pioglitazone, liraglutide, vitamin E, OCA and pentoxifylline have proven some histological improvements in NASH and omega 3-PUFAs were shown to decrease liver fat, but no specific recommendation can be made for treatment of NASH. Perhaps a combination of agents that target different pathogenic pathways are needed to better control disease progression, but more robust evidence for these agents is still needed.
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Affiliation(s)
- Simona Cernea
- a Department M3/Internal Medicine IV , University of Medicine and Pharmacy , Târgu Mureş , Romania.,b Diabetes, Nutrition and Metabolic Diseases Outpatient Unit , Emergency County Clinical Hospital , Târgu Mureş , Romania
| | - Avivit Cahn
- c Diabetes Unit, Department of Internal Medicine , Hadassah Hebrew University Hospital , Jerusalem , Israel.,d Endocrinology and Metabolism Unit, Department of Internal Medicine , Hadassah University Hospital , Jerusalem , Israel
| | - Itamar Raz
- c Diabetes Unit, Department of Internal Medicine , Hadassah Hebrew University Hospital , Jerusalem , Israel
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13
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France M, Kwok S, Soran H, Williams S, Ho JH, Adam S, Canoy D, Liu Y, Durrington PN. Liver Fat Measured by MR Spectroscopy: Estimate of Imprecision and Relationship with Serum Glycerol, Caeruloplasmin and Non-Esterified Fatty Acids. Int J Mol Sci 2016; 17:ijms17071089. [PMID: 27399690 PMCID: PMC4964465 DOI: 10.3390/ijms17071089] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/21/2016] [Revised: 06/28/2016] [Accepted: 06/30/2016] [Indexed: 12/27/2022] Open
Abstract
Magnetic resonance spectroscopy (MRS) is a non-invasive method for quantitative estimation of liver fat. Knowledge of its imprecision, which comprises biological variability and measurement error, is required to design therapeutic trials with measurement of change. The role of adipocyte lipolysis in ectopic fat accumulation remains unclear. We examined the relationship between liver fat content and indices of lipolysis, and determine whether lipolysis reflects insulin resistance or metabolic liver disease. Imprecision of measurement of liver fat was estimated from duplicate measurements by MRS at one month intervals. Patients provided fasting blood samples and we examined the correlation of liver fat with indices of insulin resistance, lipolysis and metabolic liver disease using Kendall Tau statistics. The coefficient of variation of liver fat content was 14.8%. Liver fat was positively related to serum insulin (T = 0.48, p = 0.042), homeostasis model assessment (HOMA)-B% (T = -0.48, p = 0.042), and body mass index (BMI) (T = 0.59, p = 0.012); and inversely related to HOMA-S% (T = -0.48, p = 0.042), serum glycerol (T = -0.59, p = 0.014), and serum caeruloplasmin (T = 0.055, p = 0.047). Our estimate of total variability in liver fat content (14.8%) is nearly twice that of the reported procedural variability (8.5%). We found that liver fat content was significantly inversely related to serum glycerol but not to non-esterified fatty acids (NEFA), suggesting progressive suppression of lipolysis. Reduction of caeruloplasmin with increasing liver fat may be a consequence or a cause of hepatic steatosis.
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Affiliation(s)
- Michael France
- Department of Clinical Biochemistry, Cobbett House, Central Manchester Foundation Trust, Oxford Road, Manchester M13 9WL, UK.
| | - See Kwok
- Cardiovascular Trials Unit, The Old St Mary's Hospital, Hathersage Road, Oxford Road, Manchester M13 9WL, UK.
| | - Handrean Soran
- Department of Medicine, Central Manchester Foundation Trust, Oxford Road, Manchester M13 9WL, UK.
| | - Steve Williams
- Department of Imaging Science, University of Manchester, Oxford Road, Manchester M13 9PT, UK.
| | - Jan Hoong Ho
- Department of Medicine, Central Manchester Foundation Trust, Oxford Road, Manchester M13 9WL, UK.
| | - Safwaan Adam
- Department of Imaging Science, University of Manchester, Oxford Road, Manchester M13 9PT, UK.
| | - Dexter Canoy
- Cancer Epidemiology Unit, University of Oxford, Richard Doll Building, Roosevelt Drive, Oxford OX3 7LF, UK.
| | - Yifen Liu
- School of Biomedicine, 3rd floor, Core Technology Facility, 46 Grafton Street, Manchester M13 9NT, UK.
| | - Paul N Durrington
- School of Biomedicine, 3rd floor, Core Technology Facility, 46 Grafton Street, Manchester M13 9NT, UK.
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Abstract
There is worldwide epidemic of non-alcoholic fatty liver disease (NAFLD). NAFLD is a clinical entity related to metabolic syndrome. Majority of the patients are obese but the disease can affect non-obese individuals as well. Metabolic factors and genetics play important roles in the pathogenesis of this disorder. The spectrum of disorders included in NAFLD are benign macrovesicular hepatic steatosis, non-alcoholic steatohepatitis, hepatic fibrosis, cirrhosis of liver and hepatocellular carcinoma. Although the disease remains asymptomatic most of the time, it can slowly progress to end stage liver disease. It will be the most common indication of liver transplantation in the future. It is diagnosed by abnormal liver chemistry, imaging studies and liver biopsy. As there are risks of potential complications during liver biopsy, many patients do not opt for liver biopsy. There are some noninvasive scoring systems to find out whether patients have advanced hepatic fibrosis. At the present time, there are limited treatment options which include lifestyle modification to loose weight, vitamin E and thioglitazones. Different therapeutic agents are being investigated for optimal management of this entity. There are some studies done on incretin based therapies in patients with NAFLD. Other potential agents will be silent information regulator protein Sirtuin and antifibrotic monoclonal antibody Simtuzumab against lysyl oxidase like molecule 2. But they are still in the investigational phase.
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Affiliation(s)
- Monjur Ahmed
- Monjur Ahmed, Division of Gastroenterology and Hepatology, Department of Internal Medicine, Thomas Jefferson University, Philadelphia, PA 19107, United States
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15
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Ahmed M. Non-alcoholic fatty liver disease in 2015. World J Hepatol 2015; 7:1450-1459. [PMID: 26085906 PMCID: PMC4462685 DOI: 10.4254/wjh.v7.i11.1450] [Citation(s) in RCA: 128] [Impact Index Per Article: 12.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/23/2014] [Revised: 04/18/2015] [Accepted: 04/28/2015] [Indexed: 02/06/2023] Open
Abstract
There is worldwide epidemic of non-alcoholic fatty liver disease (NAFLD). NAFLD is a clinical entity related to metabolic syndrome. Majority of the patients are obese but the disease can affect non-obese individuals as well. Metabolic factors and genetics play important roles in the pathogenesis of this disorder. The spectrum of disorders included in NAFLD are benign macrovesicular hepatic steatosis, non-alcoholic steatohepatitis, hepatic fibrosis, cirrhosis of liver and hepatocellular carcinoma. Although the disease remains asymptomatic most of the time, it can slowly progress to end stage liver disease. It will be the most common indication of liver transplantation in the future. It is diagnosed by abnormal liver chemistry, imaging studies and liver biopsy. As there are risks of potential complications during liver biopsy, many patients do not opt for liver biopsy. There are some noninvasive scoring systems to find out whether patients have advanced hepatic fibrosis. At the present time, there are limited treatment options which include lifestyle modification to loose weight, vitamin E and thioglitazones. Different therapeutic agents are being investigated for optimal management of this entity. There are some studies done on incretin based therapies in patients with NAFLD. Other potential agents will be silent information regulator protein Sirtuin and antifibrotic monoclonal antibody Simtuzumab against lysyl oxidase like molecule 2. But they are still in the investigational phase.
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Affiliation(s)
- Monjur Ahmed
- Monjur Ahmed, Division of Gastroenterology and Hepatology, Department of Internal Medicine, Thomas Jefferson University, Philadelphia, PA 19107, United States
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16
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Sall D, Wang J, Rashkin M, Welch M, Droege C, Schauer D. Orlistat-induced fulminant hepatic failure. Clin Obes 2014; 4:342-7. [PMID: 25826164 DOI: 10.1111/cob.12075] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/26/2014] [Revised: 08/06/2014] [Accepted: 08/11/2014] [Indexed: 01/27/2023]
Abstract
Orlistat was approved by the Food and Drug Administration in 1998 and has been shown to be superior to placebo in achieving weight loss. It is generally well tolerated. However, severe liver injury has been reported. We present a case of hepatic failure in a patient taking orlistat. A 54-year-old African-American woman with hypertension presented with hepatic failure. She had noticed increasing fatigue, jaundice and confusion. She used alcohol sparingly and denied tobacco or illicit drug use, but had been taking over-the-counter orlistat for the past two months. Physical examination revealed scleral icterus, jaundice, asterixis and slow speech. Laboratory testing showed markedly abnormal liver function tests with coagulopathy. Acute viral and autoimmune serologies were negative, as was toxicology screen. Liver biopsy showed necrotic hepatic parenchyma likely secondary to drug toxicity. Based upon her clinical presentation and time course, the pattern of liver injury seen on liver biopsy and lack of an alternative plausible explanation, her liver failure was most likely associated with orlistat use. She continued to deteriorate and ultimately underwent orthotopic liver transplantation. Fourteen cases of severe liver injury associated with orlistat use have been reported, four of which are detailed in the literature. This is the second published case of liver failure associated with over-the-counter orlistat usage. Clinicians should be aware of the growing number of cases associating liver injury and orlistat use and carefully monitor their patients on this medication for signs of hepatic dysfunction.
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Affiliation(s)
- D Sall
- Department of Internal Medicine, University of Cincinnati Medical Center, Cincinnati, OH, USA
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17
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Gupte AA, Sabek OM, Fraga D, Minze LJ, Nishimoto SK, Liu JZ, Afshar S, Gaber L, Lyon CJ, Gaber AO, Hsueh WA. Osteocalcin protects against nonalcoholic steatohepatitis in a mouse model of metabolic syndrome. Endocrinology 2014; 155:4697-705. [PMID: 25279794 PMCID: PMC5393336 DOI: 10.1210/en.2014-1430] [Citation(s) in RCA: 54] [Impact Index Per Article: 4.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
Nonalcoholic fatty liver disease, particularly its more aggressive form, nonalcoholic steatohepatitis (NASH), is associated with hepatic insulin resistance. Osteocalcin, a protein secreted by osteoblast cells in bone, has recently emerged as an important metabolic regulator with insulin-sensitizing properties. In humans, osteocalcin levels are inversely associated with liver disease. We thus hypothesized that osteocalcin may attenuate NASH and examined the effects of osteocalcin treatment in middle-aged (12-mo-old) male Ldlr(-/-) mice, which were fed a Western-style high-fat, high-cholesterol diet for 12 weeks to induce metabolic syndrome and NASH. Mice were treated with osteocalcin (4.5 ng/h) or vehicle for the diet duration. Osteocalcin treatment not only protected against Western-style high-fat, high-cholesterol diet-induced insulin resistance but substantially reduced multiple NASH components, including steatosis, ballooning degeneration, and fibrosis, with an overall reduction in nonalcoholic fatty liver disease activity scores. Further, osteocalcin robustly reduced expression of proinflammatory and profibrotic genes (Cd68, Mcp1, Spp1, and Col1a2) in liver and suppressed inflammatory gene expression in white adipose tissue. In conclusion, these results suggest osteocalcin inhibits NASH development by targeting inflammatory and fibrotic processes.
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Affiliation(s)
- Anisha A Gupte
- Bioenergetics Program (A.A.G.), Houston Methodist Research Institute, Houston, Texas; Department of Surgery (O.M.S., D.F., S.A., A.O.G.), Houston Methodist Hospital, Houston, Texas 77030; Immunobiology Research Center (L.J.M.), Houston Methodist Research Institute, Houston, Texas 77030; Department of Microbiology, Immunology and Biochemistry (S.K.N.), University of Tennessee Health Science Center, Memphis, Tennessee 38163; Houston Methodist Research Institute (J.Z.L., C.J.L., W.A.H.), Methodist Diabetes and Metabolism Institute, Houston, Texas 77030; Department of Pathology (L.G.), Houston Methodist Hospital, Houston, Texas 77030; and Department of Medicine (J.Z.L., W.A.H.), Division of Endocrinology, Diabetes and Metabolism, The Ohio State University, Columbus, Ohio 43210
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Bouzianas DG, Bouziana SD, Hatzitolios AI. Potential treatment of human nonalcoholic fatty liver disease with long-chain omega-3 polyunsaturated fatty acids. Nutr Rev 2013; 71:753-71. [PMID: 24148001 DOI: 10.1111/nure.12073] [Citation(s) in RCA: 29] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022] Open
Abstract
Nonalcoholic fatty liver disease (NAFLD) is the most common chronic liver disorder in the Western world. Its prevalence has increased with the growing obesity epidemic, yet no definitive treatment has been developed, and optimal management remains a clinical challenge. Long-chain omega-3 polyunsaturated fatty acids (PUFAs) have recently been proposed as a potential treatment for liver inflammation associated with fat accumulation. PubMed literature and the ClinicalTrials.gov database were reviewed for the effects of omega-3 PUFA treatment on NAFLD, from mechanisms to the results of preclinical studies, human studies, and unreported ongoing clinical trials, using terms such as NAFLD, nonalcoholic steatohepatitis, omega-3 fatty acids, and fish oil. Articles published over the last 3-4 years were emphasized, and relevancy was ensured by scanning their abstracts. Preliminary studies have confirmed an ameliorative effect, yet the translation of promising early data into therapeutic interventions will have to await the results of larger, properly conducted, ongoing clinical trials.
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Affiliation(s)
- Dimitrios G Bouzianas
- First Propedeutic Department of Internal Medicine, Medical School, AHEPA University Hospital, Aristotle University of Thessaloniki, Thessaloniki, Macedonia, Greece
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Bacchi E, Moghetti P. Exercise for hepatic fat accumulation in type 2 diabetic subjects. Int J Endocrinol 2013; 2013:309191. [PMID: 24078810 PMCID: PMC3773947 DOI: 10.1155/2013/309191] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/01/2013] [Accepted: 07/26/2013] [Indexed: 01/10/2023] Open
Abstract
Type 2 diabetes is characterized by frequent ectopic fat accumulation in several tissues and organs. In particular, a number of studies showed that these subjects frequently have hepatic fat accumulation, which may play a role in the metabolic abnormalities typical of diabetes and has been also linked to increased risk for cardiovascular disease. In the last decade, the effect of exercise on ectopic fat content of type 2 diabetic patients has raised growing interest. However, there are only a few small randomized controlled trials on this topic. Results from these intervention studies indicate that exercise training, independent of dietary modifications, may reduce hepatic fat content and serum transaminases in these patients, suggesting that exercise per se may be an effective strategy to be combined with the traditional dietary interventions. As regards the different training modalities, there is recent evidence that both aerobic and resistance exercise may equally reduce hepatic fat accumulation in type 2 diabetic subjects. However, information regarding the effect of exercise on liver histology and fat accumulation in other ectopic sites is still very limited.
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Affiliation(s)
- Elisabetta Bacchi
- Unit of Endocrinology, Diabetes and Metabolism, Department of Medicine, University and Azienda Ospedaliera Universitaria Integrata of Verona, Piazzale Stefani 1, 37126 Verona, Italy
| | - Paolo Moghetti
- Unit of Endocrinology, Diabetes and Metabolism, Department of Medicine, University and Azienda Ospedaliera Universitaria Integrata of Verona, Piazzale Stefani 1, 37126 Verona, Italy
- *Paolo Moghetti:
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