The thrifty 'catch-up fat' phenotype: its impact on insulin sensitivity during growth trajectories to obesity and metabolic syndrome
The thrifty 'catch-up fat' phenotype: its impact on insulin sensitivity during growth trajectories to obesity and metabolic syndrome
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DOI：
10.1038/sj.ijo.0803516
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发表时间：
2006-12-01
影响因子：
4.9
通讯作者：
Montani, J-P
中科院分区：
文献类型：
--
作者：
Dulloo, A. G.;Jacquet, J.;Montani, J-P
对大型流行病学数据库的分析表明，婴儿和儿童在较年轻时表现出追赶性生长或肥胖反弹，在以后的生活中更容易患肥胖症、2型糖尿病和心血管疾病。这些生长轨迹使这些疾病的风险增加的病理生理学机制尚不清楚，但有令人信服的证据表明，追赶性生长本身的动态过程（其通常与较年轻时的肥胖反弹重叠）的特征在于高胰岛素血症和体脂肪恢复率不成比例地高于瘦肉组织（即优先的“追赶性脂肪”）。这篇论文首先关注这种优先的“追赶脂肪”表型在整个生命周期中作为肥胖和胰岛素相关并发症的危险因素的几乎无处不在的性质-不仅在早期胎儿或新生儿生长迟缓后经历追赶生长的婴儿和儿童中，或者在早产后，而且在由于饥荒而导致体重大幅下降后显示体重恢复的成人中，疾病-恶病质或周期性节食。它随后审查的证据表明，这种优先追赶脂肪主要是由能量守恒（节俭）机制通过抑制生热作用，与葡萄糖，从而避免在骨骼肌中的氧化被定向到从头脂肪生成和存储在白色脂肪组织。一个分子生理学框架，它整合了新的见解的机制，这种节俭的“追赶脂肪”表型交联与早期发展的胰岛素和瘦素抵抗。在个体的遗传结构、生命早期的编程以及随后的高能量食物和低体力活动的生活方式之间的复杂相互作用中，这种节俭的“追赶脂肪”表型--可能是为了在周期性食物短缺的狩猎采集生活方式中提高生存能力而进化的--是肥胖和聚集成胰岛素抵抗（代谢）综合征的疾病的生长轨迹中的中心事件。
The analyses of large epidemiological databases have suggested that infants and children who show catch-up growth, or adiposity rebound at a younger age, are predisposed to the development of obesity, type 2 diabetes and cardiovascular diseases later in life. The pathophysiological mechanisms by which these growth trajectories confer increased risks for these diseases are obscure, but there is compelling evidence that the dynamic process of catch-up growth per se, which often overlaps with adiposity rebound at a younger age, is characterized by hyperinsulinemia and by a disproportionately higher rate in the recovery of body fat than lean tissue (i.e. preferential 'catch- up fat'). This paper first focuses upon the almost ubiquitous nature of this preferential 'catch- up fat' phenotype across the life cycle as a risk factor for obesity and insulin-related complications - not only in infants and children who experienced catch-up growth after earlier fetal or neonatal growth retardation, or after preterm birth, but also in adults who show weight recovery after substantial weight loss owing to famine, disease-cachexia or periodic dieting. It subsequently reviews the evidence indicating that such preferential catch-up fat is primarily driven by energy conservation ( thrifty) mechanisms operating via suppressed thermogenesis, with glucose thus spared from oxidation in skeletal muscle being directed towards de novo lipogenesis and storage in white adipose tissue. A molecular - physiological framework is presented which integrates emerging insights into the mechanisms by which this thrifty 'catch- up fat' phenotype crosslinks with early development of insulin and leptin resistance. In the complex interactions between genetic constitution of the individual, programming earlier in life, and a subsequent lifestyle of energy dense foods and low physical activity, this thrifty 'catch- up fat' phenotype - which probably evolved to increase survival capacity in a hunter - gatherer lifestyle of periodic food shortages - is a central event in growth trajectories to obesity and to diseases that cluster into the insulin resistance ( metabolic) syndrome.