Division of Physiology, Department of Medicine, University of Fribourg, Switzerland.
Int J Obes (Lond). 2006 Dec;30 Suppl 4:S23-35. doi: 10.1038/sj.ijo.0803516.
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.
大规模流行病学数据库的分析表明，在较小年龄时出现追赶性生长或脂肪量反弹的婴儿和儿童，以后更容易发生肥胖、2 型糖尿病和心血管疾病。这些生长轨迹增加这些疾病风险的病理生理机制尚不清楚，但有确凿的证据表明，追赶性生长本身的动态过程，通常与较小年龄时的脂肪量反弹重叠，其特征是高胰岛素血症和体脂肪恢复速度不成比例地高于瘦组织（即优先“追赶脂肪”）。本文首先关注这种优先“追赶脂肪”表型在整个生命周期中作为肥胖和与胰岛素相关并发症的危险因素的普遍存在性——不仅在经历早期胎儿或新生儿生长迟缓或早产后追赶性生长的婴儿和儿童中，而且在因饥荒、疾病恶病质或周期性节食而大量减重后体重恢复的成年人中也是如此。随后，本文回顾了表明这种优先追赶脂肪主要是由通过抑制产热起作用的能量节约（节俭）机制驱动的证据，葡萄糖因此免于骨骼肌氧化，被引导用于从头脂肪生成和白色脂肪组织储存。提出了一个分子生理学框架，该框架整合了关于这种节俭“追赶脂肪”表型与胰岛素和瘦素抵抗早期发展交联的机制的新见解。在个体的遗传构成、生命早期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者生活方式中提高生存能力而进化而来的——是肥胖和聚集到胰岛素抵抗（代谢）综合征的疾病的生长轨迹中的一个核心事件。
