Caloric restriction and intermittent fasting alter hepatic lipid droplet proteome and diacylglycerol species and prevent diabetes in NZO mice
Caloric restriction and intermittent fasting alter hepatic lipid droplet proteome and diacylglycerol species and prevent diabetes in NZO mice
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DOI：
10.1016/j.bbalip.2015.01.013
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发表时间：
2015-05-01
影响因子：
4.8
通讯作者：
Schuermann, Annette
中科院分区：
文献类型：
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作者：
Baumeier, Christian;Kaiser, Daniel;Schuermann, Annette
已知热量限制和间歇性禁食可以改善包括人类在内的几个物种的葡萄糖稳态和胰岛素抵抗。本研究的目的是揭示这些干预措施改善胰岛素敏感性和预防2型糖尿病的潜在机制。将糖尿病易感的新西兰肥胖小鼠限制10%卡路里（CR）或每隔一天禁食（IF），并与随意（AL）喂养的对照小鼠进行比较。AL小鼠显示糖尿病患病率为43%，而CR和IF小鼠完全免受高血糖症的影响。肝脂滴的蛋白质组学分析显示，在CR和IF小鼠的样本中，PSMD 9（共激活因子Bridge-1）、MIF（巨噬细胞迁移抑制因子）、TCEB 2（转录延伸因子B（SIII），多肽2）、ACY 1（氨基酰化酶1）和FABP 5（脂肪酸结合蛋白5）的水平显著升高，GSTA 3（谷胱甘肽S-转移酶α 3）的水平显著降低。此外，IF小鼠肝脏中二酰基甘油（DAGs）的积累显著减少（P = 0.045），而CR小鼠显示出类似的趋势（P = 0.062）。特别是，9种DAG种类在响应IF时显著减少，其中DAG-40：4和DAG-40：7在CR后也显示出显著作用。这与PKC β活化降低有关，可能解释了胰岛素敏感性的改善。总之，我们的数据表明，对糖尿病的保护热量限制和间歇性禁食与脂滴蛋白质组成的调制和细胞内DAG种类的减少。(C)2015作者由爱思唯尔公司出版
Caloric restriction and intermittent fasting are known to improve glucose homeostasis and insulin resistance in several species including humans. The aim of this study was to unravel potential mechanisms by which these interventions improve insulin sensitivity and protect from type 2 diabetes. Diabetes-susceptible New Zealand Obese mice were either 10% calorie restricted (CR) or fasted every other day (IF), and compared to ad libitum (AL) fed control mice. AL mice showed a diabetes prevalence of 43%, whereas mice under CR and IF were completely protected against hyperglycemia. Proteomic analysis of hepatic lipid droplets revealed significantly higher levels of PSMD9 (co-activator Bridge-1), MIF (macrophage migration inhibitor factor), TCEB2 (transcription elongation factor B (SIII), polypeptide 2), ACY1 (aminoacylase 1) and FABP5 (fatty acid binding protein 5), and a marked reduction of GSTA3 (glutathione S-transferase alpha 3) in samples of CR and IF mice. In addition, accumulation of diacylglycerols (DAGs) was significantly reduced in livers of IF mice (P = 0.045) while CR mice showed a similar tendency (P = 0.062). In particular, 9 DAG species were significantly reduced in response to IF, of which DAG-40:4 and DAG-40:7 also showed significant effects after CR. This was associated with a decreased PKC epsilon activation and might explain the improved insulin sensitivity. In conclusion, our data indicate that protection against diabetes upon caloric restriction and intermittent fasting associates with a modulation of lipid droplet protein composition and reduction of intracellular DAG species. (C) 2015 The Authors. Published by Elsevier B.V.