Webber Jonathan
School of Medical and Surgical Sciences, University of Nottingham, Nottingham NG7 2UH, UK.
Proc Nutr Soc. 2003 May;62(2):539-43. doi: 10.1079/pns2003256.
The current epidemic of human obesity implies that whilst energy balance appears to be regulated, the extent of this regulatory process is being overwhelmed in large numbers of the population by environmental changes. Clearly, the shift towards positive energy balance reflects both alterations in energy intake and decreases in physical activity. Increased energy intake and, in particular, the rising proportion of energy from fat is linked with obesity. However, on a population level reduced levels of activity probably play the predominant role. It is apparent that individual susceptibility to weight gain varies enormously. The factors underlying this susceptibility are an area of intense research interest. Variations in BMR from that predicted appear to be linked to the propensity to gain weight. The genes responsible for this variation may include uncoupling proteins-2 and -3, with a number of studies showing a link with obesity. However, in vivo studies of these proteins have not yet demonstrated a physiological role for them that would explain the link with obesity. Non-exercise activity thermogenesis may also protect from weight gain, but the regulation of this type of thermogenesis is unclear, although the sympathetic nervous system may be important. A profusion of hormones, cytokines and neurotransmitters is involved in regulating energy intake, but whilst mutations in leptin and the melanocortin-3 receptor are responsible for rare monogenic forms of obesity, their wider role in common polygenic obesity is not known. Much current work is directed at examining the interplay between genetic background and environmental factors, in particular diet, that both lead to positive energy balance and seem to make it so hard for many obese subjects to lose weight.
当前人类肥胖的流行表明，尽管能量平衡似乎受到调节，但在大量人群中，这种调节过程的程度正被环境变化所压倒。显然，向正能量平衡的转变既反映了能量摄入的改变，也反映了身体活动的减少。能量摄入增加，特别是来自脂肪的能量比例上升，与肥胖有关。然而，在人群层面上，活动水平的降低可能起着主要作用。很明显，个体对体重增加的易感性差异极大。这种易感性背后的因素是一个备受研究关注的领域。基础代谢率（BMR）与预测值的差异似乎与体重增加的倾向有关。负责这种差异的基因可能包括解偶联蛋白-2和-3，多项研究表明它们与肥胖有关。然而，对这些蛋白质的体内研究尚未证明它们具有能解释与肥胖关联的生理作用。非运动活动产热也可能有助于防止体重增加，但这种产热类型的调节尚不清楚，尽管交感神经系统可能很重要。大量的激素、细胞因子和神经递质参与调节能量摄入，虽然瘦素和黑皮质素-3受体的突变是导致罕见单基因肥胖形式的原因，但它们在常见多基因肥胖中的更广泛作用尚不清楚。目前许多工作都致力于研究遗传背景与环境因素（特别是饮食）之间的相互作用，这些因素既导致正能量平衡，又似乎使许多肥胖者难以减肥。
