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.

Keywords: Alcohol; Lipid Dyshomeostasis; Lipogenesis; Subcutaneous Fat; Visceral Fat; White Adipose Tissue.

Fig. 1

Chronic alcohol feeding significantly reduced the mass and adipocyte size of EWAT. Male Wistar rats were fed liquid diets containing alcohol (AF) or maltose dextrin (PF) for 12 weeks. EWAT and SWAT were taken. Tissue masses (A) were weighed, adipose tissue morphology (B), and adipocyte sizes (C) were measured at 20× objective using Nikon Eclipse 55i. All values are denoted as means ± SD. Significant differences are indicated by different letters (ANOVA, p < 0.05).

Fig. 2

Chronic alcohol feeding significantly reduced the protein levels of lipogenic enzymes and regulators in EWAT. Male Wistar rats were fed liquid diets containing alcohol (AF) or maltose dextrin (PF) for 12 weeks. (A) The expressions of lipogenic enzymes and regulators in both EWAT and SWAT were measured by Western blotting. (B) The expressions of lipogenic enzymes and regulators in liver were measured by Western blotting. Expression levels of indicated proteins were quantitated by the NIH ImageJ software (Bethesda, MD). All values are denoted as means ± SD. Significant differences are indicated by different letters (ANOVA, p < 0.05).

Fig. 3

Chronic alcohol feeding significantly elevated aldehyde dehydrogenase (ALDH) activity in both EWAT and SWAT, and differentially increased aldehyde metabolic enzymes. Male Wistar rats were fed liquid diets containing alcohol (AF) or maltose dextrin (PF) for 12 weeks. (A) ALDH activity in WATs and liver was measured by colorimetric kit. (B) Protein levels of enzymes involved in alcohol and acetaldehyde metabolism in both EWAT and SWAT were measured by Western blotting. Protein levels of indicated proteins were quantitated by the NIH ImageJ software. All values are denoted as means ± SD. Significant differences are indicated by different letters (ANOVA, p < 0.05).

Fig. 4

Acetaldehyde treatment significantly reduced the expression of lipogenic enzymes and regulators in EWAT explants and in 3T3-L1 adipocytes. EWAT explants were from male Wistar rats treated in the presence or absence of 100 µmol/l of acetaldehyde for 3 days. 3T3-L1 cells were treated with 100 µmol/l acetaldehyde in the presence or absence of aldehyde dehydrogenase inhibitor, cyanamide, at concentration of 5 µmol/l for 3 days also. Ethanol (EtOH) was also used to treat 3T3-L1 cells at 200 mmol/l for 3 days. The protein levels of lipogenic enzymes and regulators in both EWAT (A), 3T3-L1 cells treated with acetaldehyde (B), or 3T3-L1 cells treated with EtOH (C) were measured by Western blotting. Band intensity was quantitated by the NIH ImageJ software. All values are denoted as means ± SD. Significant differences are indicated by different letters (t-test, p < 0.05).