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Background Alcohol consumption is the fourth leading cause of death and disability worldwide. Several cellular pathways contribute to alcohol-mediated tissue injury. Adipose tissue apart from functioning as an endocrine organ secretes several hormones and cytokines known as adipokines that are known to play a significant role in alcohol-induced tissue damage. This study was designed to test the efficacy of diallyl sulfide (DAS) in regulating the alcohol-induced outcomes on adipose tissue. Methods Male Wistar rats were fed with 36% Lieber–DeCarli liquid diet containing ethanol (EtOH) for 4 weeks. Control rats were pair-fed with isocaloric diet containing maltodextrin instead of EtOH. During the last week of feeding protocol, the EtOH-fed rat group was given 200 mg/kg body weight of DAS through diet. We also studied DAS effect on isolated human primary adipocytes. Viability of human primary adipocytes on DAS treatment was assessed by MTT assay. Malondialdehyde (MDA), a marker of oxidative stress, was measured by HPLC and the thiobarbituric acid method. Expression of inflammatory genes and lipogenic genes was studied by qRT-PCR and Western blotting. Serum inflammatory gene expression was studied by ELISA. Results Our study results showed that DAS could alleviate EtOH-induced expression levels of proinflammatory and endoplasmic reticulum (ER) stress genes and improve adipose tissue mass and adipocyte morphology in male Wistar rats fed Lieber–DeCarli diet containing 6% EtOH. Further, we showed that DAS reduced the expression of lipogenic genes and improved lipid accumulation and adipocyte mass in human primary adipocytes treated with EtOH. Subsequently, we also showed that oxidative stress, as measured by the changes in MDA levels, was reduced in both male Wistar rats and human primary adipocytes treated with EtOH plus DAS. Conclusions Our study results prove that DAS is effective in ameliorating EtOH-induced damage to adipose tissue as evidenced by the reduction brought about by DAS in oxidative stress, ER stress, and proinflammatory gene expression levels. DAS treatment also regulated lipogenic gene expression levels, thereby reducing free fatty acid release. In conclusion, this study has clinical implications with respect to alcohol-induced adipose tissue injury among alcohol users.

Alcohol consumption has been in existence in the world for many centuries and it is the major cause of death and injury worldwide. Alcoholic liver disease (ALD) is caused due to excess and chronic alcohol intake. Studies across the globe have identified several pathways leading to ALD. Adipose tissue which has been considered as an energy storage organ is also found to play a major role in ALD progression by secreting hormones and cytokines known as adipokines or adipocytokines. Ethanol affects the metabolic and innate immune activities of adipose tissue contributing to alcohol-induced injury of the tissues.We aimed at 1) summarizing the metabolism and progression of ALD 2) summarizing about the structure and effect of ethanol induced oxidative stress on adipose tissue 3) reviewing the available data on the effect of ethanol on adipose tissue mass and adipokine secretion in both rodent models and alcoholic patients.The article is summarized based on the original literature and reviews in studying the effect of ethanol on adipose tissue.Studies on alcoholic patients and rodent models has shown that chronic ethanol consumption reduces adipose tissue mass and causes CYP2E1 mediated oxidative stress and inflammation of adipose tissue. Further hyperlipolysis is observed in adipose tissue that leads to excess fatty acid release that gets transported and deposited in the liver resulting in hepatic steatosis.Studies show that adipose tissue plays a major role in the progression of ALD. So understanding of the mechanisms linking ethanol induced adipose tissue injury with ALD progression would help us in identifying potential therapeutic targets.

Background and Objectives: Consumption of alcohol has been in existence in the world for many centuries. Every year the use of alcohol kills 2.5 million people accounting for almost 4% of the deaths in the world. Progression of alcoholic liver disease is a multifactorial process involving a number of genetic, nutritional and environmental factors. Alcohol is metabolized via alcohol dehydrogenase pathway, the microsomal ethanol-oxidizing system involving the Cytochrome P450 2E1 (CYP2E1) enzyme, and catalase pathway. Chronic ethanol consumption activates CYP2E1 enzyme resulting in reactive oxygen species formation leading to oxidative stress and endoplasmic reticulum stress. Excessive oxidative stress results in membrane lipid peroxidation and formation of toxic aldehydes. We hypothesize that ethanol induced oxidative and endoplasmic reticulum stress disrupt the secretion of adipokines from adipose tissue and adipokines are known to play a major role in the progression of alcoholic liver disease. Objectives: 1. Studying the over expression and inhibition of CYP2E1 on ethanol induced oxidative stress and on adipokine levels. 2. Investigating the effects of ethanol on the endoplasmic reticulum (ER) function and the influence of ER stress on the posttranslational modifications of adipokines. 3. Identification of protein adducts formed by lipid peroxidation products and investigating the resistance to the metabolic actions of adipokines by hepatic nonparenchymal cells. Results: Several passages of 3T3L1 cell line and RAW 264.7 cell line were established. The cell lines were exposed to different concentrations of ethanol. Preliminary data pertaining to the oxidative stress markers was obtained. Quantitative real time PCR studies of CYP2E1, IL-6, leptin, resistin genes are being carried out. Conclusion:Understanding the molecular mechanisms of ethanol mediated liver injury will aid in identification of new integrative approaches as it relates to alcoholic liver