Leptin Deficiency And Appetite Control

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It seems clear that for the majority of obese people, the OB protein (leptin) system is not a major cause of rapid or massive weight gain.

However, for certain individuals very low levels of leptin (or the absence of leptin) may constitute a major risk factor. Recently a number of individuals have come to light. For example, two young cousins have been studied who displayed marked hyper-phagia from a very early age. This hyperphagia took the form of a constant hunger accompanied by food cravings and a continuous demand for food (17). The eldest of the two cousins had reached a body weight of more than 90 kg by the age of 9. Her serum leptin level (like that of the cousin) was very low, and subsequently a mutation in the gene for leptin was revealed. This finding seems to implicate leptin (OB protein) in the control of the drive for food; that is, in the expression of hunger and active food seeking rather than with satiety or the short-term inhibition over eating. Leptin therefore appears to modulate the tonic signal associated with the translation of need into drive; when leptin levels are low or absent then the drive is unleashed and results in voracious food seeking. The MC4 receptor is also part of the same system and the absence of this receptor also abolishes restraint over appetite leading to massive hyperphagia. This phenomenon is quite different from the removal of a single satiety signal which would lead only to an increase in meal size or a modest increase in meal frequency.

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