Dulloo A G
Department of Medicine, Division of Physiology, University of Fribourg, Switzerland.
Horm Res. 2006;65 Suppl 3:90-7. doi: 10.1159/000091512. Epub 2006 Apr 10.
Catch-up growth during infancy and childhood is increasingly recognized as a major risk factor for later development of insulin-related complications and chronic diseases, namely abdominal obesity, type 2 diabetes and cardiovascular disease. As catch-up growth per se is characterized by insulin resistance, hyperinsulinaemia and an accelerated rate of fat storage (i.e., catch-up fat) even in the absence of hyperphagia, the possibility arises that suppressed thermogenesis in certain organs/tissues - for the purpose of enhancing the efficiency of catch-up fat - also plays a role in the pathophysiological consequences of catch-up growth. Here, the evidence for the existence of an adipose-specific control of thermogenesis, the suppression of which contributes to catch-up fat, is reviewed. Recent findings suggest that such suppression of thermogenesis is accompanied by hyperinsulinaemia, insulin resistance in skeletal muscle and insulin hyperresponsiveness in adipose tissue, all of which precede the appearance of excess body fat, central fat distribution and elevations in intramyocellular triglyceride or circulating lipid concentrations. These findings underscore a role for suppressed thermogenesis per se as an early event in the pathophysiology of catch-up growth. It is proposed that, in its evolutionary adaptive role to spare glucose for the rapid rebuilding of an adequate fat reserve (for optimal survival capacity during intermittent famine), suppressed thermogenesis in skeletal muscle constitutes a thrifty phenotype that confers to the phase of catch-up growth its high sensitivity to the development of insulin resistance and hyperinsulinaemia. In the context of the complex interactions between earlier reprogramming and a modern lifestyle characterized by nutritional abundance and low physical activity, this thrifty 'catch-up fat phenotype' is a central event that predisposes individuals with catch-up growth to abdominal obesity, type 2 diabetes and cardiovascular disease.
婴幼儿期的追赶生长越来越被认为是后期发生胰岛素相关并发症和慢性病（即腹型肥胖、2型糖尿病和心血管疾病）的主要危险因素。由于追赶生长本身的特点是即使在没有食欲亢进的情况下也存在胰岛素抵抗、高胰岛素血症和脂肪储存加速（即追赶性肥胖），因此有可能是某些器官/组织中为提高追赶性肥胖效率而抑制的产热，也在追赶生长的病理生理后果中起作用。在此，我们综述了存在脂肪特异性产热控制的证据，这种控制的抑制会导致追赶性肥胖。最近的研究结果表明，这种产热抑制伴随着高胰岛素血症、骨骼肌胰岛素抵抗和脂肪组织胰岛素高反应性，所有这些都先于体脂过多、中心性脂肪分布以及肌内甘油三酯或循环脂质浓度升高的出现。这些发现强调了产热抑制本身作为追赶生长病理生理学早期事件的作用。有人提出，在其进化适应性作用中，为了节省葡萄糖以快速重建足够的脂肪储备（以便在间歇性饥荒期间具有最佳生存能力），骨骼肌中产热抑制构成了一种节俭表型，使追赶生长阶段对胰岛素抵抗和高胰岛素血症的发展具有高度敏感性。在早期重编程与以营养丰富和体力活动少为特征的现代生活方式之间复杂的相互作用背景下，这种节俭的“追赶性肥胖表型”是一个核心事件，使经历追赶生长的个体易患腹型肥胖、2型糖尿病和心血管疾病。
