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The neurobiology and genetics of eating and weight regulation
Author(s) -
Hebebrand J.
Publication year - 2008
Publication title -
journal of intellectual disability research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.941
H-Index - 104
eISSN - 1365-2788
pISSN - 0964-2633
DOI - 10.1111/j.1365-2788.2008.01118_1.x
Subject(s) - leptin , obesity , biology , genetics , anorexia nervosa , eating disorders , polygene , bulimia nervosa , leptin receptor , melanocortin 4 receptor , psychology , endocrinology , medicine , gene , melanocortin , psychiatry , quantitative trait locus , receptor
Over the past 15 years tremendous advances have been made in the elucidation of pathways relevant to eating behaviour and body weight regulation. It has become evident that these pathways are intricately interwoven with those underlying mood and anxiety regulation, motor activity, cognition, sleep, fertility and libido. In addition, advances have been made in determining genetic variation underlying inter‐individual differences in body weight. To illustrate these novel findings we will focus on: 1) Monogenic and oligogenic obesity: The underlying genes were initially detected in animal models. Based on mutation screens of the human homologues functionally relevant mutations were detected in the genes coding for leptin, its receptors and the melanocortin‐4 receptor (MC4R). The effect of such mutations is large. Leptin gene mutations lead to hyperphagia and subsequently obesity. Hyperphagia, albeit of a substantially reduced magnitude, has also been observed in obese children with mutations in the MC4R . 2) Polygenic obesity: The advent of genome wide association studies has led to the detection of single polygenes, among which FTO features prominently. Typically, a variant predisposing to obesity accounts for a body weight elevated by on average 200 to 1500 grams. Such polygenes act in concert to account for inter‐individual differences in body weight. 3) Leptin has been shown to have profound implications for anorexia nervosa. Serum leptin levels in this eating disorders are annormaly low. The hypoleptinemia entails a down‐regulation of the hypothalamic‐pituitary‐gonadal‐axis, which underlies the amenorrhea characteristic of anorexia nervosa. Furthermore, the hypoleptinemia induces hyperactivity in a rat model of anorexia nervosa. In patients, leptin levels are inversely correlated with activity levels.