Regulation of fat storage via suppressed thermogenesis: A thrifty phenotype that predisposes individuals with catch-up growth to insulin resistance and obesity
Regulation of fat storage via suppressed thermogenesis: A thrifty phenotype that predisposes individuals with catch-up growth to insulin resistance and obesity
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DOI：
10.1159/000091512
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发表时间：
2006-01-01
期刊：
影响因子：
--
通讯作者：
Dulloo, AG
中科院分区：
文献类型：
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作者：
Dulloo, AG
婴儿期和儿童期的追赶性生长越来越被认为是以后发生胰岛素相关并发症和慢性疾病的主要危险因素，如腹部肥胖、2型糖尿病和心血管疾病。由于追赶生长本身的特征是胰岛素抵抗、高胰岛素血症和脂肪储存速率加快（即，追赶性脂肪），即使在没有过度摄食的情况下，也出现了这样的可能性，即为了提高追赶性脂肪的效率而抑制某些器官/组织中的产热作用也在追赶性生长的病理生理学后果中起作用。在这里，证据存在的脂肪特异性控制产热，抑制其有助于追赶脂肪，进行审查。最近的研究结果表明，这种抑制产热伴随着高胰岛素血症，骨骼肌中的胰岛素抵抗和脂肪组织中的胰岛素高反应性，所有这些都先于多余的身体脂肪，中央脂肪分布和肌细胞内甘油三酯或循环脂质浓度升高的出现。这些发现强调了抑制产热本身作为追赶生长的病理生理学的早期事件的作用。有人建议，在其进化适应作用，备用葡萄糖快速重建足够的脂肪储备（间歇性饥荒期间的最佳生存能力），抑制骨骼肌产热构成了一个节俭的表型，赋予追赶增长阶段的胰岛素抵抗和高胰岛素血症的发展的高敏感性。在早期重编程和以营养丰富和低体力活动为特征的现代生活方式之间的复杂相互作用的背景下，这种节俭的“追赶脂肪表型”是使具有追赶生长的个体容易患腹部肥胖、2型糖尿病和心血管疾病的中心事件。
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, namelyabdominal 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 catchup 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.