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bioRxiv · 10.1101/453761

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

Coker, C. R.·Aguilar, E. A.·Snyder, A. E.·Bingaman, S. S.·Graziane, N. M.·Browning, K. N.·Arnold, A. C.·Silberman, Y.
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Abstract

Alcoholism and high fat diet (HFD)-induced obesity individually promote insulin resistance and glucose intolerance in clinical populations, increasing risk for metabolic diseases. Conversely, animal studies, typically utilizing forced/continuous alcohol (EtOH) access, tend to show that EtOH intake mitigates HFD-induced effects on insulin and glucose function, while HFD decreases voluntary EtOH intake in continuous access models. However, the impact of HFD on intermittent EtOH intake 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 assess resultant impact on insulin sensitivity and glucose tolerance. In the first experiment, mice had Unlimited Access EtOH (UAE)+HFD (n=15; HFD=60% calories from fat, 10% EtOH v/v, ad libitum) or UAE+Chow (n=15; control diet=16% calories from fat, ad libitum) for 6 weeks. UAE+HFD mice had lower EtOH preference, consumed significantly less EtOH, and were insulin resistant and hyperglycemic compared with UAE+Chow mice. In the second experiment, mice had Limited Access EtOH (LAE, 4 hrs/d; 3 d/wk)+HFD (n=15) or LAE+Chow (n=15) with increasing EtOH concentrations (10%, 15%, 20%). LAE+HFD mice had no difference in total EtOH consumption compared to LAE+Chow mice, but exhibited hyperglycemia, insulin resistance, and glucose intolerance. In the third experiment, mice had intermittent HFD access (single 24 hr session/week) with limited access to EtOH (iHFD-E, 4hrs/d; 4 d/wk) (n=10). iHFD-E mice displayed binge eating behaviors and consumed significantly more EtOH than mice given ad libitum chow or HFD, suggesting transfer of binge eating to binge drinking behaviors. Although iHFD-E mice did not have significantly altered body composition, they developed insulin insensitivity and glucose intolerance. These results suggest that access schedules determine the impact of HFD on EtOH consumption and resultant metabolic dysfunction.

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Coker, C. R., Aguilar, E. A., Snyder, A. E., Bingaman, S. S., Graziane, N. M., Browning, K. N., Arnold, A. C., Silberman, Y.. 2018-10-25. Access schedules mediate the impact of high fat diet on ethanol intake in mice.. https://doi.org/10.1101/453761

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