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Physiological Reviews, Vol. 79, No. 2, April 1999, pp. 451-480
Copyright ©1999 by the American Physiological Society
Institute of Physiology, University of Lausanne, Lausanne, Switzerland
Jéquier, Eric and
Luc Tappy.
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 development of human obesity is a field of great actual interest
that needs further research. Present evidences suggest that genetic and
environmental factors influence eating behavior of people prone to
obesity and that diets that are high in fat or energy dense undermine
body weight regulation by promoting an overconsumption of energy
relative to need.
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