Department of Human and Animal Physiology, Wageningen University, Marijkeweg 40, 6709 GP Wageningen, PO Box 338, 6700 AH Wageningen, The Netherlands.
J Mol Endocrinol. 2011 Aug;47(1):81-97.
High energy intake and, specifically, high dietary fat intake challenge the mammalian metabolism and correlate with many metabolic disorders such as obesity and diabetes. However, dietary restriction (DR) is known to prevent the development of metabolic disorders. The current western diets are highly enriched in fat, and it is as yet unclear whether DR on a certain high-fat (HF) diet elicits similar beneficial effects on health. In this research, we report that HF-DR improves metabolic health of mice compared with mice receiving the same diet on an ad libitum basis (HF-AL). Already after five weeks of restriction, the serum levels of cholesterol and leptin were significantly decreased in HF-DR mice, whereas their glucose sensitivity and serum adiponectin levels were increased. The body weight and measured serum parameters remained stable in the following 7 weeks of restriction, implying metabolic adaptation. To understand the molecular events associated with this adaptation, we analyzed gene expression in white adipose tissue (WAT) with whole genome microarrays. HF-DR strongly influenced gene expression in WAT; in total, 8643 genes were differentially expressed between both groups of mice, with a major role for genes involved in lipid metabolism and mitochondrial functioning. This was confirmed by quantitative real-time reverse transcription-PCR and substantiated by increase in mitochondrial density in WAT of HF-DR mice. These results provide new insights in the metabolic flexibility of dietary restricted animals and suggest the development of substrate efficiency.
高能量摄入，特别是高脂肪饮食，会给哺乳动物的新陈代谢带来挑战，并与许多代谢紊乱相关，如肥胖和糖尿病。然而，人们已知饮食限制（DR）可预防代谢紊乱的发生。目前的西方饮食富含高脂肪，尚不清楚在特定高脂肪（HF）饮食上进行 DR 是否会对健康产生类似的有益影响。在这项研究中，我们报告称 HF-DR 可改善与接受自由进食（HF-AL）相同饮食的小鼠的代谢健康。在限制饮食五周后，HF-DR 小鼠的血清胆固醇和瘦素水平显著降低，而其葡萄糖敏感性和血清脂联素水平升高。在接下来的 7 周限制饮食期间，体重和测量的血清参数保持稳定，表明存在代谢适应。为了了解与这种适应相关的分子事件，我们使用全基因组微阵列分析了白色脂肪组织（WAT）中的基因表达。HF-DR 强烈影响 WAT 中的基因表达；在两组小鼠之间，总共 8643 个基因的表达存在差异，其中涉及脂质代谢和线粒体功能的基因起主要作用。这通过定量实时逆转录聚合酶链式反应（qRT-PCR）得到证实，并通过 HF-DR 小鼠 WAT 中线粒体密度的增加得到证实。这些结果为饮食限制动物的代谢灵活性提供了新的见解，并提示了底物效率的发展。
