Visceral White Adipose Tissue is Susceptible to Alcohol-Induced Lipodystrophy in Rats: Role of Acetaldehyde

Abstract

Background Chronic alcohol exposure causes lipid dyshomeostasis at the adipose-liver axis, reducing lipid storage in white fat and increasing lipid deposit in the liver. Previous studies have shown that visceral fat, rather than subcutaneous fat, is a risk factor for metabolic diseases. This study was conducted to determine whether chronic alcohol exposure differentially affects lipid metabolism in visceral (epididymal) and subcutaneous fat, and the mechanisms underlying the alcohol effects. Methods Male Wistar rats were pair-fed the Lieber-DeCarli control or alcohol liquid diet for 12 weeks to determine the effects of alcohol on the white fat. Tissue explants culture and 3T3-L1 culture were conducted to define the role of acetaldehyde in alcohol-induced adipose tissue dysfunction. Results Chronic alcohol feeding significantly reduced visceral fat mass and down-regulated peroxisome proliferator activator receptor-γ and CCAAT/enhancer binding protein-α, 2 important transcription factors in regulation of lipogenesis. The protein levels of lipogenic enzymes including phospho-ATP-citrate lyase, acetyl-CoA carboxylase, fatty acid synthase, lipin1, and diacylglycerol acyltransferase 2 in the visceral fat were reduced. In contrast, chronic alcohol exposure did not affect subcutaneous fat mass and had less effect on the protein levels of lipogenic enzymes and regulators. Accordingly, the visceral fat showed a lower protein level of aldehyde detoxification enzymes compared to the subcutaneous fat. Acetaldehyde treatment to either visceral fat explants or 3T3-L1 adipocytes produced similar effects on lipogenic enzymes and regulators as observed in animal model. Conclusions These results demonstrated that visceral fat is more susceptible to alcohol toxicity compared to subcutaneous fat, and disruption of adipose lipogenesis contributes to the pathogenesis of alcoholic lipodystrophy.

Potential Molecular Mechanism of Probiotics in Alcoholic Liver Disease

“…In vitro experiment on 3T3-L1 with alcohol revealed an overexpression for CYP2E1, decreased adiponectin secretion similar to in vivo experiment in rat [61]. In another experiment, 3T3 L1 adipocytes with acetaldehyde resulted in decrease lipogenic regulators like PPAR γ, lipid [67].…”

“…A study demonstrated that chronic alcohol exposure enhances WAT lipolysis in association with activation of major adipose triglyceride hydrolases [72]. CYP2E1 is also expressed in adipose tissue, thus up regulation of CYP2E1 on alcohol consumption leads to oxidative stress and affect the metabolism [67]. In vitro experiment on 3T3-L1 with alcohol revealed an overexpression for CYP2E1, decreased adiponectin secretion similar to in vivo experiment in rat [61].…”

“…In vivo experiment of mice for the reflective effect of the metabolism on chronic alcohol consumption showed decreased weight of epididymal white adipose tissue (WAT), perirenal adipose tissue, mesenteric adipose tissue [46], and adipocyte size [63][64]. The former study has shown variation in the result depending on the pair-feeding technique [65][66], a difference in the macronutrient composition of the diet, dose of alcohol, animals receiving complete nutritional adequate liquid diet [67]. In vivo study, performed with a high dose of alcohol (5 g/kg/day) and low fat (10%) chow diet showed elevated WAT and perirenal lipid depots [68].…”

Alcohol, Adipose Tissue and Lipid Dysregulation

“…Consistent with their findings that alcohol suppresses lipolysis via the β-AR pathway [39,40], Kang et al, 2006 found that alcohol decreases HSL Ser660 phosphorylation [39]. Only one other investigation has reported a similar decrease in eWAT from rats after 12 weeks of an alcohol-containing liquid diet [19]. Instead, the majority of work shows HSL phosphorylation, activity or mRNA to be increased [7,9,11,12,14,15,18,45,46] or at least unchanged by alcohol [7,14,18,45].…”

“…In contrast, chronic alcohol feeding in rats does not consistently increase fat mass potentially due to improper pair-feeding techniques [16,17], differences in macronutrient composition of the diets (i.e., high fat versus low fat), doses of alcohol used, feeding methods (liquid diet, in water, through gastric tube), or the interaction of these methodological variances in the different adipose tissue depots (eWAT vs. sWAT). Of those animals receiving alcohol as part of a complete nutritionally adequate liquid diet, visceral and subcutaneous adipose tissue mass was unchanged [18,19], while eWAT was either unchanged [20] or decreased [19,21]. A high dose of alcohol (5 g/kg/day) administered via a gastric tube to animals consuming a low fat (10%) chow diet increased eWAT and perirenal depots [22].…”