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

Apr 1, 2020Alcohol (Fayetteville, N.Y.)

How access timing changes the effects of a high-fat diet on alcohol drinking and blood sugar control in mice

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Abstract

Mice with unlimited access to a high-fat diet (HFD) consumed significantly less ethanol and displayed insulin resistance and hyperglycemia compared to those with unlimited access to a control diet.

Mice given unlimited access to ethanol and HFD showed reduced ethanol intake alongside metabolic dysfunction.
Mice with limited access to ethanol and HFD exhibited similar ethanol consumption to those on a control diet but had hyperglycemia and insulin resistance.
Intermittent access to HFD led to binge eating-like behaviors in mice, who subsequently consumed significantly more ethanol than those on a control diet.
Binge eating behaviors were associated with insulin insensitivity and glucose intolerance in the mice.
Different access schedules to HFD and ethanol appear to influence both ethanol consumption and metabolic health outcomes.

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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.

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

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