Effects of Chronic Ethanol Intake on High‐Fat Diet Induced Metabolic Dysfunction in Mice

Abstract

High‐fat diet (HFD) induced obesity is associated with insulin resistance and is a major risk factor for numerous co‐morbidities such as type II diabetes. Conflicting clinical and preclinical evidence suggests that moderate alcohol consumption improves insulin sensitivity in obese subjects, and therefore may act to protect against obesity‐related metabolic comorbidities. However, the impact of free choice ethanol (EtOH) intake and HFD consumption on insulin action and glucose homeostasis in animal models remains unclear. Therefore, the overall goal of these studies was to determine if long‐term EtOH intake may alter insulin and glucose function in a mouse model of HFD induced obesity. Six‐week old male C57Bl/6J mice were given ad libitum access to HFD (n=10; 60% calories from fat) or control diet (Chow, n=10; 10% calories from fat) for two weeks. Mice were then given increasing volumes of EtOH (3%, 7%, and 10%) over one week as an EtOH‐ramp initiation period for subsequent 24‐hour access to a two‐bottle choice of water or 10% EtOH (vol/vol, in water). Body mass, EtOH and water intake, and EtOH preference was assessed every 24 hours for six weeks. HFD mice had significantly higher body mass compared to Chow mice (p<0.001). By the end of the study, Chow mice consumed significantly more EtOH than mice on HFD (p<0.001) and had higher preference towards EtOH (p<0.001). At the end of treatment, we measured 4‐hour fasting glucose levels and performed insulin tolerance tests (to examine the ability of intraperitoneal insulin to suppress blood glucose levels) in half of the mice in each group. These metabolic data were compared to weight and aged matched mice given HFD or Chow without EtOH access. Insulin sensitivity was significantly reduced in HFD mice (p=0.003; two‐way ANOVA), and EtOH consumption did not alter HFD‐induced insulin resistance. Furthermore, there appeared to be a trend for increased 4 hour fasting glucose levels in HFD (185.8±9.4), HFD+EtOH (176±25.9) and Chow+EtOH (177.8±21.6) groups compared to Chow alone (156.4±6.2). Together, these results suggest that moderate EtOH drinking in a two‐bottle choice model does not improve insulin sensitivity in HFD mice, but that higher levels of EtOH intake in control diet mice may cause impaired glucose homeostasis that may not be due to changes in insulin sensitivity.Support or Funding InformationPenn State Dept of Neural and Behavioral Science, NIH grants AA022937 and HL122507This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.