Access schedules mediate the impact of high fat diet on ethanol intake in mice.

High fat diet (HFD)-induced obesity and alcoholism each individually promote insulin resistance and glucose intolerance, and together increase risk for Type II diabetes in the clinical setting. Conversely, animal studies, typically utilizing forced/continuous alcohol (EtOH) access, tend to show that EtOH intake decreases HFD-induced effects on insulin and glucose function, while HFD decreases EtOH intake. Intermittent access increases EtOH intake, but HFD effects on intermittent EtOH and resultant changes to metabolic function are not well characterized. The present studies sought to determine if HFD alters EtOH intake in male C57Bl/6J mice given differing two-bottle choice EtOH access schedules, and to determine the impact of HFD and scheduled EtOH intake on insulin sensitivity and glucose tolerance. In the first cohort, mice were given Unlimited Access EtOH (UAE)+HFD (n=15; HFD=60% calories from fat, 10% EtOH v/v, ad libitum) or UAE+Chow (n=15; standard mouse chow=10% calories from fat, ad libitum) for 6 weeks. UAE+HFD mice gained significantly more weight, had lower EtOH preference, consumed significantly less EtOH, and were insulin resistant and hyperglycemic compared with UAE+Chow mice. In the second cohort, mice were given Limited Access EtOH (LAE, 4 hrs/d; 3 d/wk)+HFD (n=5) or LAE+Chow (n=5) with increasing EtOH concentrations (10%, 15%, 20%). LAE+HFD mice gained more weight than LAE+Chow mice and had lower 10% EtOH preference, with no difference in total EtOH consumption at any EtOH concentration. LAE+HFD mice had seemingly normal insulin sensitivity but profound hyperglycemia and glucose intolerance. These results suggest that access schedules determine the impact of HFD on EtOH consumption and HFD+EtOH-induced metabolic dysfunction.