Access schedules mediate the impact of high fat diet on ethanol intake and insulin and glucose function in mice

Abstract

Alcoholism and high fat diet (HFD)-induced obesity individually promote insulin resistance and glucose intolerance in clinical populations, increasing risk for metabolic diseases. HFD can also stimulate alcohol intake in short-term clinical studies. Unfortunately, there is currently a disconnect between animal models and the clinical findings, as animal studies typically show that HFD decreases ethanol intake while ethanol intake mitigates HFD-induced effects on insulin and glucose dysfunction. However, most previous animal studies utilized forced or continuous HFD and/or ethanol. In three experiments we sought to determine whether HFD (HFD = 60% calories from fat) vs. control diet (chow = 16% fat) alters voluntary two-bottle choice ethanol intake in male C57Bl/6J mice given differing access schedules for 6-7 weeks, and we assessed the resultant impact on metabolic function via insulin and glucose tolerance tests. Experiment 1: Unlimited Access Ethanol + HFD (UAE + HFD; n = 15; 10% ethanol v/v, ad libitum diet and ethanol) or UAE + Chow (n = 15). Experiment 2: Limited Access Ethanol + HFD (LAE + HFD; n = 15; ethanol = 4 h/day; 3 days/week, ad libitum diet) or LAE + Chow (n = 15) with increasing ethanol concentrations (10%, 15%, 20%). Experiment 3: Intermittent HFD with limited access to ethanol (iHFD-E; HFD = single 24-h session/week; ethanol = 4 h/day; 4 days/week) (n = 10). UAE + HFD mice consumed significantly less ethanol and were insulin-resistant and hyperglycemic compared with UAE + Chow mice. LAE + HFD mice consumed ethanol similarly to LAE + Chow mice, but exhibited hyperglycemia, insulin resistance, and glucose intolerance. iHFD-E mice displayed binge eating-like behaviors and consumed significantly more ethanol than mice given ad libitum chow or HFD. iHFD-E mice did not have significantly altered body composition, but developed insulin insensitivity and glucose intolerance. These findings suggest that access schedules influence HFD effects on ethanol consumption and resultant metabolic dysfunction, ethanol intake does not improve HFD-induced metabolic dysfunction, and binge eating-like behaviors can transfer to binge drinking behaviors.

Keywords: Binging; Ethanol; High fat diet; Ingestive behaviors; Metabolic dysfunction.