Division of Pediatric Endocrinology and Diabetology, University Children's Hospital, Zurich, Switzerland.
Children's Research Center, University Children's Hospital, Zurich, Switzerland.
Am J Physiol Endocrinol Metab. 2019 Nov 1;317(5):E773-E782. doi: 10.1152/ajpendo.00187.2019. Epub 2019 Sep 10.
Four days of high-fat diet (HFD) feeding are sufficient to induce glucose intolerance and hepatic steatosis in mice. While prolonged HFD-induced metabolic complications are partly mediated by increased food intake during the light (inactive) phase, such a link has not yet been established in short-term HFD-fed mice. Herein, we hypothesized that a short bout of HFD desynchronizes feeding behavior, thereby contributing to glucose intolerance and hepatic steatosis. To this end, 12-wk-old C57BL/6J littermates were fed a HFD for 4 days either ad libitum or intermittently. Intermittent-fed mice were fasted for 8 h during their inactive phase. Initiation of HFD led to an immediate increase in food intake already during the first light phase. Moreover, glucose tolerance was significantly impaired in ad libitum- but not in intermittent HFD-fed mice, indicating that desynchronized feeding behavior contributes to short-term HFD-induced glucose intolerance. Of note, overall food intake was similar between the groups, as was body weight. However, intermittent HFD-fed mice revealed higher fat depot weights. Phosphorylation of hormone sensitivity lipase and free fatty acid release from isolated adipocytes were significantly elevated, suggesting increased lipolysis in intermittent HFD-fed mice. Moreover, hepatic mRNA expression of lipogenetic enzymes and liver triglyceride levels were significantly increased in intermittent HFD-fed mice. Importantly, food deprivation decreased respiratory exchange ratio promptly in intermittent- but not in ad libitum HFD-fed mice. In conclusion, retaining a normal feeding pattern prevented HFD-induced impairment of metabolic flexibility in short-term HFD-fed mice.
四天的高脂肪饮食（HFD）喂养足以诱导小鼠出现葡萄糖不耐受和肝脂肪变性。虽然长时间的 HFD 诱导的代谢并发症部分是由在光照（不活动）期增加食物摄入所介导的，但这种联系尚未在短期 HFD 喂养的小鼠中建立。在此，我们假设短暂的 HFD 打乱了进食行为，从而导致葡萄糖不耐受和肝脂肪变性。为此，12 周龄的 C57BL/6J 同窝仔鼠被喂食 HFD4 天，要么自由进食，要么间歇性进食。间歇性进食的小鼠在不活动期禁食 8 小时。开始 HFD 喂养后，即使在第一个光照期，食物摄入量也会立即增加。此外，在自由进食的小鼠中，葡萄糖耐量明显受损，但在间歇性 HFD 喂养的小鼠中则没有，这表明进食行为的不同步导致了短期 HFD 诱导的葡萄糖不耐受。值得注意的是，两组的总食物摄入量和体重相似。然而，间歇性 HFD 喂养的小鼠脂肪储存量更高。激素敏感脂肪酶的磷酸化和分离脂肪细胞中游离脂肪酸的释放显著增加，提示间歇性 HFD 喂养的小鼠脂肪分解增加。此外，间歇性 HFD 喂养的小鼠肝脏中脂肪生成酶的 mRNA 表达和肝甘油三酯水平显著增加。重要的是，间歇性 HFD 喂养的小鼠在禁食后呼吸交换率迅速下降，但自由进食 HFD 喂养的小鼠则没有。总之，保持正常的进食模式可以防止短期 HFD 喂养的小鼠出现 HFD 诱导的代谢灵活性受损。
