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Jiang X, Wang H, Nie K, Gao Y, Chen S, Tang Y, Wang Z, Su H, Dong H. Targeting lipid droplets and lipid droplet-associated proteins: a new perspective on natural compounds against metabolic diseases. Chin Med 2024; 19:120. [PMID: 39232826 PMCID: PMC11373146 DOI: 10.1186/s13020-024-00988-w] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/17/2024] [Accepted: 08/22/2024] [Indexed: 09/06/2024] Open
Abstract
BACKGROUND Lipid droplet (LD) is a metabolically active organelle, which changes dynamically with the metabolic state and energy requirements of cells. Proteins that either insert into the LD phospholipid monolayer or are present in the cytoplasm, playing a crucial role in lipid homeostasis and signaling regulation, are known as LD-associated proteins. METHODS The keywords "lipid droplets" and "metabolic diseases" were used to obtain literature on LD metabolism and pathological mechanism. After searching databases including Scopus, OVID, Web of Science, and PubMed from 2013 to 2024 using terms like "lipid droplets", "lipid droplet-associated proteins", "fatty liver disease", "diabetes", "diabetic kidney disease", "obesity", "atherosclerosis", "hyperlipidemia", "natural drug monomers" and "natural compounds", the most common natural compounds were identified in about 954 articles. Eventually, a total of 91 studies of 10 natural compounds reporting in vitro or in vivo studies were refined and summarized. RESULTS The most frequently used natural compounds include Berberine, Mangostin, Capsaicin, Caffeine, Genistein, Epigallocatechin-3-gallate, Chlorogenic acid, Betaine, Ginsenoside, Resveratrol. These natural compounds interact with LD-associated proteins and help ameliorate abnormal LDs in various metabolic diseases. CONCLUSION Natural compounds involved in the regulation of LDs and LD-associated proteins hold promise for treating metabolic diseases. Further research into these interactions may lead to new therapeutic applications.
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Affiliation(s)
- Xinyue Jiang
- Institute of Integrated Traditional Chinese and Western Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Hongzhan Wang
- Institute of Integrated Traditional Chinese and Western Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Kexin Nie
- Institute of Integrated Traditional Chinese and Western Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Yang Gao
- Institute of Integrated Traditional Chinese and Western Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Shen Chen
- Institute of Integrated Traditional Chinese and Western Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Yueheng Tang
- Department of Rehabilitation Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Zhi Wang
- Department of Integrated Traditional Chinese and Western Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Hao Su
- Department of Integrated Traditional Chinese and Western Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Hui Dong
- Institute of Integrated Traditional Chinese and Western Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
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Awad LZ, El-Mahallawy HS, Abdelnaeim NS, Mahmoud MMA, Dessouki AA, ElBanna NI. Role of dietary Spirulina platensis and betaine supplementation on growth, hematological, serum biochemical parameters, antioxidant status, immune responses, and disease resistance in Nile tilapia. FISH & SHELLFISH IMMUNOLOGY 2022; 126:122-130. [PMID: 35613669 DOI: 10.1016/j.fsi.2022.05.040] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 03/28/2022] [Revised: 05/14/2022] [Accepted: 05/19/2022] [Indexed: 06/15/2023]
Abstract
Spirulina platensis is, a freshwater microalga, broadly used worldwide. It not only stimulates the immune systems of aquatic organisms but also provides a protein-rich diet and commonly used in the manufacture of aquafeeds. This study was planned to evaluate the growth performance, hepato-renal, and immune response biomarkers of Spirulina and Betaine on Nile tilapia (Oreochromis niloticus) and their protective effect against infection with Aeromonas hydrophila. O. niloticus juveniles (20.22 ± 0.86 g) were divided into four groups (n = 10 per replicate). For 8 weeks, the first and second groups (TS&TB) were fed with 0.5% and 0.3% concentrations of Spirulina and Betaine supplemented diets, respectively; the third group (TSB) was fed with a Spirulina and Betaine mixed diet; the fourth group was fed with a basal diet (without supplementation, T0), which served as control. Dietary inclusion of Spirulina and Betaine significantly improved (P ˂ 0.05) the weight gain, final weight, and food conversion ratio, especially in the TS group. The activities of hepatic malonaldehyde were unchanged in TS & TSB groups and the muscular significantly decreased (P ˂ 0.05) in the same groups, while both increased in the TB group; meanwhile, levels of glutathione reductase were significantly upregulated in all treated groups. Serum interleukins, TNF- alpha, and IL-10 levels were also significantly reduced in all treatment groups. A significant protective power against pathogenic Aeromonas infection was evidenced in all treated groups. Findings in this study highlight the reputation of Spirulina and Betaine as immunostimulants and protective agents against A. hydrophila infection in O. niloticus.
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Affiliation(s)
- Laila Z Awad
- Aquaculture Diseases Control Department, Fish Farming and Technology Institute, Suez Canal University, Ismailia, 41522, Egypt
| | - Heba S El-Mahallawy
- Department of Animal Hygiene, Zoonoses and Animal Behaviour and Management - Faculty of Veterinary Medicine, Suez Canal University, Ismailia, 41522, Egypt
| | - Noha S Abdelnaeim
- Department of Clinical Pathology, Faculty of Veterinary Medicine, Suez Canal University, Ismailia, 41522, Egypt
| | - Manal M A Mahmoud
- Department of Nutrition and Clinical Nutrition, Faculty of Veterinary Medicine, Suez Canal University, Ismailia, 41522, Egypt
| | - Amina A Dessouki
- Department of Pathology, Faculty of Veterinary Medicine, Suez Canal University, Ismailia, 41522, Egypt
| | - Noha I ElBanna
- Aquaculture Diseases Control Department, Fish Farming and Technology Institute, Suez Canal University, Ismailia, 41522, Egypt.
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Lei Z, Chen X, Cao F, Guo Q, Wang J. Phytochemicals and bioactivities of Goji (
Lycium barbarum
L. and
Lycium chinense
Mill.) leaves and their potential applications in the food industry: a review. Int J Food Sci Technol 2021. [DOI: 10.1111/ijfs.15507] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/28/2022]
Affiliation(s)
- Zilun Lei
- Department of Food Science and Engineering College of Light Industry and Food Engineering Nanjing Forestry University Nanjing 210037 China
| | - Xianqiang Chen
- Department of Food Science and Engineering College of Light Industry and Food Engineering Nanjing Forestry University Nanjing 210037 China
| | - Fuliang Cao
- Co‐innovation Center for the Sustainable Forestry in Southern China College of Forestry Nanjing Forestry University Nanjing 210037 China
| | - Qirong Guo
- Co‐innovation Center for the Sustainable Forestry in Southern China College of Forestry Nanjing Forestry University Nanjing 210037 China
| | - Jiahong Wang
- Department of Food Science and Engineering College of Light Industry and Food Engineering Nanjing Forestry University Nanjing 210037 China
- Co‐innovation Center for the Sustainable Forestry in Southern China College of Forestry Nanjing Forestry University Nanjing 210037 China
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Rehman A, Mehta KJ. Betaine in ameliorating alcohol-induced hepatic steatosis. Eur J Nutr 2021; 61:1167-1176. [PMID: 34817678 PMCID: PMC8921017 DOI: 10.1007/s00394-021-02738-2] [Citation(s) in RCA: 18] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/07/2021] [Accepted: 11/03/2021] [Indexed: 01/15/2023]
Abstract
Alcohol-associated liver disease (AALD) is one of most common chronic liver diseases. Hepatic steatosis is the earliest stage in AALD pathological spectrum, reversible by alcohol abstinence. Untreated steatosis can progress to steatohepatitis, fibrosis and/or cirrhosis. Considering the difficulties in achieving complete abstinence, challenges in disease reversal at advanced stages, high costs of AALD management and lack of standardised prescribed medications for treatment, it is essential to explore low-cost natural compounds that can target AALD at an early stage and halt or decelerate disease progression. Betaine is a non-hazardous naturally occurring nutrient. Here, we address the mechanisms of alcohol-induced hepatic steatosis, the role of betaine in reversing the effects i.e., its action against hepatic steatosis in animal models and humans, and the associated cellular and molecular processes. Accordingly, the review discusses how betaine restores the alcohol-induced reduction in methylation potential by elevating the levels of S-adenosylmethionine and methionine. It details how betaine reinstates alcohol-induced alterations in the expressions and/or activities of protein phosphtase-2A, FOXO1, PPAR-α, AMPK, SREBP-1c, fatty acid synthase, diacylglycerol transferase-2, adiponectin and nitric oxide. Interrelationships between these factors in preventing de novo lipogenesis, reducing hepatic uptake of adipose-tissue-derived free fatty acids, promoting VLDL synthesis and secretion, and restoring β-oxidation of fatty acids to attenuate hepatic triglyceride accumulation are elaborated. Despite its therapeutic potential, very few clinical trials have examined betaine’s effect on alcohol-induced hepatic lipid accumulation. This review will provide further confidence to conduct randomised control trials to enable maximum utilisation of betaine’s remedial properties to treat alcohol-induced hepatic steatosis.
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Affiliation(s)
- Aisha Rehman
- Faculty of Life Sciences and Medicine, King's College London, London, UK
| | - Kosha J Mehta
- Centre for Education, Faculty of Life Sciences and Medicine, King's College London, London, UK.
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Effect of Betaine Supplementation on Liver Tissue and Ultrastructural Changes in Methionine-Choline-Deficient Diet-Induced NAFLD. MICROSCOPY AND MICROANALYSIS 2021; 26:997-1006. [PMID: 32782033 DOI: 10.1017/s1431927620024265] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
Nonalcoholic fatty liver disease (NAFLD) represents a hepatic manifestation of metabolic syndrome. The aim of this study was to examine the effect of betaine on ultrastructural changes in the mouse liver with methionine- and choline-deficient (MCD) diet-induced NAFLD. Male C57BL/6 mice were divided into groups: Control-fed with standard chow, BET-standard chow supplemented with betaine (1.5% w/v drinking water), MCD-fed with MCD diet, and MCD + BET-MCD diet with betaine supplementation for 6 weeks. Liver samples were taken for pathohistology and transmission electron microscopy. The MCD diet-induced steatosis, inflammation, and balloon-altered hepatocytes were alleviated by betaine. MCD diet induced an increase in mitochondrial size versus the control group (p < 0.01), which was decreased in the betaine-treated group. In the MCD diet-fed group, the total mitochondrial count decreased versus the control group (p < 0.01), while it increased in the MCD + BET group versus MCD (p < 0.01). Electron microscopy showed an increase in the number of autophagosomes in the MCD and MCD + BET group versus control, and a significant difference in autophagosomes number was detected in the MCD + BET group by comparison with the MCD diet-treated group (p < 0.05). Betaine decreases the number of enlarged mitochondria, alleviates steatosis, and increases the number of autophagosomes in the liver of mice with NAFLD.
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Arumugam MK, Paal MC, Donohue TM, Ganesan M, Osna NA, Kharbanda KK. Beneficial Effects of Betaine: A Comprehensive Review. BIOLOGY 2021; 10:456. [PMID: 34067313 PMCID: PMC8224793 DOI: 10.3390/biology10060456] [Citation(s) in RCA: 110] [Impact Index Per Article: 27.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 03/31/2021] [Revised: 05/06/2021] [Accepted: 05/19/2021] [Indexed: 02/05/2023]
Abstract
Medicinal herbs and many food ingredients possess favorable biological properties that contribute to their therapeutic activities. One such natural product is betaine, a stable, nontoxic natural substance that is present in animals, plants, and microorganisms. Betaine is also endogenously synthesized through the metabolism of choline or exogenously consumed through dietary intake. Betaine mainly functions as (i) an osmolyte and (ii) a methyl-group donor. This review describes the major physiological effects of betaine in whole-body health and its ability to protect against both liver- as well as non-liver-related diseases and conditions. Betaine's role in preventing/attenuating both alcohol-induced and metabolic-associated liver diseases has been well studied and is extensively reviewed here. Several studies show that betaine protects against the development of alcohol-induced hepatic steatosis, apoptosis, and accumulation of damaged proteins. Additionally, it can significantly prevent/attenuate progressive liver injury by preserving gut integrity and adipose function. The protective effects are primarily associated with the regulation of methionine metabolism through removing homocysteine and maintaining cellular SAM:SAH ratios. Similarly, betaine prevents metabolic-associated fatty liver disease and its progression. In addition, betaine has a neuroprotective role, preserves myocardial function, and prevents pancreatic steatosis. Betaine also attenuates oxidant stress, endoplasmic reticulum stress, inflammation, and cancer development. To conclude, betaine exerts significant therapeutic and biological effects that are potentially beneficial for alleviating a diverse number of human diseases and conditions.
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Affiliation(s)
- Madan Kumar Arumugam
- Research Service, Veterans Affairs Nebraska-Western Iowa Health Care System, Omaha, NE 68105, USA; (MK.A.); (M.C.P.); (T.M.D.J.); (M.G.); (N.A.O.)
- Department of Internal Medicine, University of Nebraska Medical Center, Omaha, NE 68198, USA
| | - Matthew C. Paal
- Research Service, Veterans Affairs Nebraska-Western Iowa Health Care System, Omaha, NE 68105, USA; (MK.A.); (M.C.P.); (T.M.D.J.); (M.G.); (N.A.O.)
- Department of Internal Medicine, University of Nebraska Medical Center, Omaha, NE 68198, USA
| | - Terrence M. Donohue
- Research Service, Veterans Affairs Nebraska-Western Iowa Health Care System, Omaha, NE 68105, USA; (MK.A.); (M.C.P.); (T.M.D.J.); (M.G.); (N.A.O.)
- Department of Internal Medicine, University of Nebraska Medical Center, Omaha, NE 68198, USA
- Department of Biochemistry & Molecular Biology, University of Nebraska Medical Center, Omaha, NE 68198, USA
| | - Murali Ganesan
- Research Service, Veterans Affairs Nebraska-Western Iowa Health Care System, Omaha, NE 68105, USA; (MK.A.); (M.C.P.); (T.M.D.J.); (M.G.); (N.A.O.)
- Department of Internal Medicine, University of Nebraska Medical Center, Omaha, NE 68198, USA
| | - Natalia A. Osna
- Research Service, Veterans Affairs Nebraska-Western Iowa Health Care System, Omaha, NE 68105, USA; (MK.A.); (M.C.P.); (T.M.D.J.); (M.G.); (N.A.O.)
- Department of Internal Medicine, University of Nebraska Medical Center, Omaha, NE 68198, USA
| | - Kusum K. Kharbanda
- Research Service, Veterans Affairs Nebraska-Western Iowa Health Care System, Omaha, NE 68105, USA; (MK.A.); (M.C.P.); (T.M.D.J.); (M.G.); (N.A.O.)
- Department of Internal Medicine, University of Nebraska Medical Center, Omaha, NE 68198, USA
- Department of Biochemistry & Molecular Biology, University of Nebraska Medical Center, Omaha, NE 68198, USA
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Liu W, Xia M, Yang L, Wang Z, Wang R, Shi Y. Development and optimization of a method for determining betaine and trigonelline in the fruits of Lycium species by using solid-phase extraction combined with high-performance liquid chromatography-diode array detector. J Sep Sci 2020; 43:2073-2078. [PMID: 32129569 DOI: 10.1002/jssc.201901124] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/02/2019] [Revised: 02/23/2020] [Accepted: 02/27/2020] [Indexed: 11/07/2022]
Abstract
Betaine is an essential nutrient for humans and a source of methyl donors for methionine and S-adenosylmethionine formation, and it is used as a biomarker for pharmacological activities and to evaluate the quality of Lycium species and common foods. However, because of its special structural features, poor ultraviolet-chromophore, and high polarity, the existing methods for betaine extraction and quantification cannot provide higher extraction efficiency, better sensitivity, or resolution degree. A simple, fast, and efficient high-performance liquid chromatography-diode array detector coupled with solid-phase extraction was adopted for simultaneous separation and quantification of betaine in four types of Lycium species. The results revealed that after degreasing with dichloromethane, extraction with 80% ethanol (pH adjusted to 1.0 with hydrochloric acid), and elution with aluminum oxide (OH- form), the improvement in the average yield rate of betaine was thrice of that of the existing methods. In addition, trigonelline was identified as the interfering substance of betaine for the first time in Lycium species, and betaine and trigonelline were simultaneously separated and quantified. Furthermore, their chemical characteristics and content distribution in different Lycium species were carried out.
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Affiliation(s)
- Wenjing Liu
- School of Pharmacy, Shanghai University of Traditional Chinese Medicine, Shanghai, P. R. China
| | - Mengqin Xia
- School of Pharmacy, Shanghai University of Traditional Chinese Medicine, Shanghai, P. R. China
| | - Li Yang
- Institute of Interdisciplinary Integrative Medicine Research, Shanghai University of Traditional Chinese Medicine, Shanghai, P. R. China
- The MOE key laboratory of Standardization of Chinese Medicines, Institute of Chinese Materia Medica, Shanghai University of Traditional Chinese Medicine, Shanghai, P. R. China
| | - Zhengtao Wang
- The MOE key laboratory of Standardization of Chinese Medicines, Institute of Chinese Materia Medica, Shanghai University of Traditional Chinese Medicine, Shanghai, P. R. China
| | - Rui Wang
- School of Pharmacy, Shanghai University of Traditional Chinese Medicine, Shanghai, P. R. China
| | - Yanhong Shi
- The MOE key laboratory of Standardization of Chinese Medicines, Institute of Chinese Materia Medica, Shanghai University of Traditional Chinese Medicine, Shanghai, P. R. China
- Institute of TCM International Standardization, Shanghai University of Traditional Chinese Medicine, Shanghai, P. R. China
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Yang W, Xie Y, Song B, Xia C, Tang C, Li J. Effects of aging and menopause on pancreatic fat fraction in healthy women population: A strobe-compliant article. Medicine (Baltimore) 2019; 98:e14451. [PMID: 30762758 PMCID: PMC6408125 DOI: 10.1097/md.0000000000014451] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/05/2023] Open
Abstract
Pancreatic fat fraction has been shown to increase in many pathological situations. However, pancreatic fat fraction and its physiological changes in healthy women are still unclear. The aim of this study is to investigate the effect of aging and menopause on pancreatic fat fraction in healthy female population.This was a cross-sectional study. A phantom of fat-water mixtures was established. One hundred sixty-seven healthy women (20-70 years) were recruited. Fat fraction was quantified with double-echo chemical shift magnetic resonance imaging with T1 and T2* correction. The association between measured and actual fat fractions was determined with Pearson correlation. Linear regression analysis was used to establish the calibration curve. Fat fractions were analyzed via analysis of variance.A significant positive linear correlation was revealed between the measured and actual fat fractions on the phantom (r = 0.991, P < .001). There was no significant difference in fat fractions among caput, corpus, and cauda of the pancreas. Pancreatic fat fraction remained constant during the age of 20 to 40 years (4.41 ± 0.79%) but significantly increased during the ages of 41 to 50 and 51 to 70 years (7.49 ± 1.10% and 9.43 ± 1.51%, respectively, P < .001). Moreover, pancreatic fat fractions of the healthy women aged 41 to 70 years were still significantly higher than these in the groups aged 20 to 40 years when postmenopausal healthy women were removed (P < .001). For volunteers aged 46 to 49 years, pancreatic fat fraction of the postmenopausal women was significantly increased compared with that of their premenopausal counterparts (P < .001).We found that an even distribution of pancreatic fat in healthy women, aging and menopause as 2 independent risk factors for pancreatic steatosis, a fatty infiltration in the pancreas beginning in the fifth decade in women.
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Affiliation(s)
| | - Yi Xie
- Department of Gastroenterology
| | - Bin Song
- Department of Radiology, West China Hospital, Sichuan University, Chengdu, Sichuan, P.R. China
| | - Chunchao Xia
- Department of Radiology, West China Hospital, Sichuan University, Chengdu, Sichuan, P.R. China
| | | | - Jing Li
- Department of Gastroenterology
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Catanzaro R, Cuffari B, Italia A, Marotta F. Exploring the metabolic syndrome: Nonalcoholic fatty pancreas disease. World J Gastroenterol 2016; 22:7660-7675. [PMID: 27678349 PMCID: PMC5016366 DOI: 10.3748/wjg.v22.i34.7660] [Citation(s) in RCA: 131] [Impact Index Per Article: 14.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/04/2016] [Revised: 07/25/2016] [Accepted: 08/10/2016] [Indexed: 02/06/2023] Open
Abstract
After the first description of fatty pancreas in 1933, the effects of pancreatic steatosis have been poorly investigated, compared with that of the liver. However, the interest of research is increasing. Fat accumulation, associated with obesity and the metabolic syndrome (MetS), has been defined as “fatty infiltration” or “nonalcoholic fatty pancreas disease” (NAFPD). The term “fatty replacement” describes a distinct phenomenon characterized by death of acinar cells and replacement by adipose tissue. Risk factors for developing NAFPD include obesity, increasing age, male sex, hypertension, dyslipidemia, alcohol and hyperferritinemia. Increasing evidence support the role of pancreatic fat in the development of type 2 diabetes mellitus, MetS, atherosclerosis, severe acute pancreatitis and even pancreatic cancer. Evidence exists that fatty pancreas could be used as the initial indicator of “ectopic fat deposition”, which is a key element of nonalcoholic fatty liver disease and/or MetS. Moreover, in patients with fatty pancreas, pancreaticoduodenectomy is associated with an increased risk of intraoperative blood loss and post-operative pancreatic fistula.
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