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

Access schedules mediate the impact of high fat diet on ethanol intake and insulin and glucose function in mice.
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DOI:
10.1016/j.alcohol.2020.03.007
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发表时间:
2020-08
期刊:
Alcohol (Fayetteville, N.Y.)
影响因子:
--
通讯作者:
Silberman Y
Silberman Y
中科院分区:
其他
文献类型:
--
作者:
Coker CR;Aguilar EA;Snyder AE;Bingaman SS;Graziane NM;Browning KN;Arnold AC;Silberman Y

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在临床人群中,酒精中毒和高脂肪饮食(HFD)诱导的肥胖分别促进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也可以刺激酒精摄入。不幸的是,目前动物模型和临床结果之间存在脱节,因为动物研究通常表明HFD减少乙醇摄入量,而乙醇摄入量减轻HFD引起的胰岛素和葡萄糖功能障碍的影响。然而,大多数先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%来自脂肪的热量)与对照饮食(Chow=16%脂肪)是否会改变雄性C57Bl/6J小鼠在6-7周的不同摄入计划中自愿选择的两瓶乙醇摄入量,并通过胰岛素和葡萄糖耐量测试评估对代谢功能的影响。试验1:无限量乙醇+HFD (UAE+HFD, n=15; 10%乙醇v/v,任意日粮和乙醇)或UAE+Chow (n=15)。实验2:随着乙醇浓度(10%、15%、20%)的增加,限制接触乙醇+HFD (LAE+HFD, n=15;乙醇= 4小时/天;3天/周,自由饲粮)或LAE+Chow (n=15)。实验3:间歇性HFD与有限的乙醇(iHFD-E; HFD=单一24小时疗程/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减少,胰岛素抵抗和高血糖。LAE+HFD小鼠消耗乙醇与LAE+Chow小鼠相似,但表现出高血糖、胰岛素抵抗和葡萄糖耐受不良。iHFD-E小鼠表现出暴饮暴食的行为,比随意喂食或喂食HFD的小鼠消耗更多的乙醇。iHFD-E小鼠的身体成分没有明显改变,但出现了胰岛素不敏感和葡萄糖耐受不良。这些研究结果表明,摄入时间会影响HFD对乙醇消耗的影响以及由此导致的代谢功能障碍,乙醇摄入不会改善HFD诱导的代谢功能障碍,并且暴饮暴食样行为可以转化为酗酒行为。
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 if 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 assessed 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 hrs/d; 3 d/wk, 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 hr session/week; ethanol= 4hrs/d; 4 d/wk) (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 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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