(P13-17-26) Chronic Alcohol Increases Circulating Lipids in Obese Female Mice.

Objectives: Obesity is commonplace in the United States and is characterized by a state of metabolic dysfunction due in part to the overabundance of adipose tissue. Likewise, over half of adults in the US consume alcohol. While the consumption of a low dose of alcohol may provide metabolic benefits and/or resistance to weight gain during obesity, this work will determine the effects of a chronically high dose of alcohol on metabolic and adipose tissue health in obese mice.

Methods: Female mice consumed either a low-fat (LFD) or high-fat diet (HFD) for 15 weeks prior to alcohol exposure to establish obesity. Ethanol (EtOH) was then introduced in their drinking water: 5% EtOH (v/v) for 3 days, 10% for 3 days, 15% for 4 days, and 20% for the remaining 27 weeks. mRNA expression was measured in perigonadal fat.

Results: Body weight after 15 weeks of HFD was elevated compared to LFD. After 27 weeks of alcohol intake, bodyweight was similar to control within each diet. Fat mass (measured by EchoMRI and perigonadal tissue mass) was higher in HFD mice regardless of alcohol intake. HFD also led to metabolic dysfunction, as the area under the curve during a glucose tolerance test was elevated with HFD, while no further effects of alcohol were observed. Circulating triglycerides and VLDL were highest in obese mice consuming alcohol, while cholesterol was not augmented by alcohol during obesity. Carbohydrate and fat oxidation were greatest in HFD mice with no additional effect of alcohol. In the adipose tissue, the mRNA expression of Lpl and Hsl were not different with HFD or EtOH. There was a main effect for Fasn, Cd36 and Ppar-α to be lower after HFD. IL-6 was similar across groups.

Conclusions: These findings show that long-term HFD-induced obesity leads to clear metabolic dysfunction in female mice, reflected by increased body weight and fat mass, impaired glucose tolerance, and abnormal levels of lipids (cholesterol and triglycerides) in the blood, regardless of alcohol intake. In adipose tissue, HFD reduced the expression of Ppar-α, Fasn, and Cd36, implying that fatty acid uptake may be reduced along with lowered lipid synthesis or adipogenesis. Interestingly, chronic alcohol consumption did not significantly worsen diet-induced changes in adipose tissue gene expression, nor did it significantly impact body weight.

Funding Sources: Florida State University Council on Research and Creativity