PATHOGENESIS OF RESISTANCE TO WEIGHT GAIN

虽然可能有遗传和环境因素，但人类肥胖症的发病机制仍不确定。 本研究的目的是确定可能导致脂肪细胞募集或肥大的因素，并将这些因素的存在与能量代谢的变化相关联。 我们推测，由于脂肪细胞基因表达的改变，抵抗体重增加的个体缺乏招募脂肪细胞和/或启动脂肪细胞肥大的能力，从而采用替代代谢途径来扩大能量。16名受试者每天过量进食1000千卡，超过体重维持要求。 静息能量消耗和食物热效应的变化不能解释脂肪增加的变化。非运动活动产热（NEAT）的增加占每日总支出增加的三分之二，足以解释我们检测到的脂肪储存的十倍范围，并直接预测过度喂养对脂肪增加的抵抗力。 我们的结论是，当人类过度进食时，非运动活动产热的激活可能导致多余能量的耗散以保持苗条，并且未能激活NEAT导致现成的脂肪增加和肥胖倾向。

The pathogenesis of obesity in man remains undetermined although there are likely to be genetic and environmental components. The purpose of this study is to identify factors that may be responsible for adipocyte recruitment or hypertrophy and to correlate the presence of these factors with changes in energy metabolism. We hypothesize that individuals who are resistant to weight gain lack the ability to recruit adipocytes and/or initiate adipocyte hypertrophy because of altered adipocyte gene expression and thereby employ alternative metabolic pathways to expand energy. Sixteen subjects were overfed by 1000 kcal/day in excess of weight maintenance requirements. Changes in resting energy expenditure and thermic effect of food could not account for the changes in fat gain. Increases in non-exercise activity thermogenesis (NEAT) accounted for two thirds of the increases in total daily expenditure, were sufficiently diverse to explain the ten-fold range in fat storage we detected and directly predicted resistance to fat gain with over-feeding. We concluded that as humans over-eat, activation of non-exercise activity thermogenesis can result in dissipation of excess energy to preserve leanness and that failure to active NEAT resulted in ready fat gain and predisposition to obesity.