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.

中文翻译：

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访问时间表介导了高脂肪饮食对小鼠乙醇摄入量以及胰岛素和葡萄糖功能的影响。

酒精中毒和高脂肪饮食 (HFD) 诱导的肥胖分别促进临床人群的胰岛素抵抗和葡萄糖耐受不良，增加代谢疾病的风险。在短期临床研究中，HFD 还可以刺激酒精摄入。不幸的是，目前动物模型与临床发现之间存在脱节，因为动物研究通常表明 HFD 会减少乙醇摄入量，而乙醇摄入量会减轻 HFD 对胰岛素和葡萄糖功能障碍的影响。然而，大多数以前的动物研究使用强制或连续 HFD 和/或乙醇。在三个实验中，我们试图确定 HFD（HFD = 60% 来自脂肪的卡路里）与对照饮食（食物 = 16% 脂肪）是否会改变雄性 C57Bl/6J 小鼠自愿两瓶选择乙醇的摄入量，因为 6- 7 周，我们通过胰岛素和葡萄糖耐量测试评估了由此产生的对代谢功能的影响。实验 1：无限制使用乙醇 + HFD（阿联酋 + HFD；n = 15；10% 乙醇 v/v，随意饮食和乙醇）或阿联酋 + Chow（n = 15）。实验 2：有限使用乙醇 + HFD（LAE + HFD；n = 15；乙醇 = 4 小时/天；3 天/周，随意饮食）或 LAE + Chow（n = 15），乙醇浓度增加（10%， 15%、20%）。实验 3：间歇性 HFD，乙醇有限（iHFD-E；HFD = 单次 24 小时会话/周；乙醇 = 4 小时/天；4 天/周）（n = 10）。与UAE + Chow 小鼠相比，UAE + HFD 小鼠消耗的乙醇明显更少，并且具有胰岛素抵抗和高血糖症。LAE + HFD 小鼠与 LAE + Chow 小鼠类似地消耗乙醇，但表现出高血糖、胰岛素抵抗和葡萄糖耐受不良。iHFD-E 小鼠表现出类似暴饮暴食的行为，并且比随意进食或 HFD 的小鼠消耗更多的乙醇。iHFD-E 小鼠的身体成分没有显着改变，但出现了胰岛素不敏感和葡萄糖耐受不良。这些发现表明，访问时间表会影响 HFD 对乙醇消耗和由此产生的代谢功能障碍的影响，乙醇摄入不会改善 HFD 引起的代谢功能障碍，暴饮暴食行为可以转移到暴饮暴食行为。