Regulation of Body Weight in Humans

作者：Eric Jéquier, Luc Tappy · 发表于：Physiological Reviews · 年份：1999 · DOI：10.1152/physrev.1999.79.2.451 · 被引用次数：375 · 研究领域：Regulation of Appetite and Obesity、Biochemical Analysis and Sensing Techniques、Adipose Tissue and Metabolism

The mechanisms involved in body weight regulation in humans include genetic, physiological, and behavioral factors. Stability of body weight and body composition requires that energy intake matches energy expenditure and that nutrient balance is achieved. Human obesity is usually associated with high rates of energy expenditure. In adult individuals, protein and carbohydrate stores vary relatively little, whereas adipose tissue mass may change markedly. A feedback regulatory loop with three distinct steps has been recently identified in rodents: 1) a sensor that monitors the size of adipose tissue mass is represented by the amount of leptin synthesized by adipose cells (a protein encoded by the ob gene) which determines the plasma leptin levels; 2) hypothalamic centers, with specific leptin receptors, which receive and integrate the intensity of the signal; and 3) effector systems that influence the two determinants of energy balance, i.e., energy intake and energy expenditure. With the exception of a few very rare cases, the majority of obese human subjects have high plasma leptin levels that are related to the size of their adipose tissue mass. However, the expected regulatory responses (reduction in food intake and increase in energy expenditure) are not observed in obese individuals. Thus obese humans are resistant to the effect of endogenous leptin, despite unaltered hypothalamic leptin receptors. Whether defects in the leptin signaling cascade play a role in the develop...