[Molecular endocrinology of hereditary obesity].
The hypothalamic disorders of obesity include hyperphagia, a low central orthosympathetic tone (with reduced thermogenesis), vagal hyperinsulinism, low serotonin efficacy, a hyperactive hypothalamo-hypophyseal-adrenal axis, a hypoactive GHRH-GH-IGF axis and hypogonadism of central origin. Hyperlipogenesis, glucose intolerance and excessive gluconeogenesis are secondary features. Most frequently the hypothalamic ARC reacts poorly to the leptin hypersecreted by adipose tissue, so that the local synthesis of NPY is unchecked. Fortunately, two prostaglandins derived from dietary arachidonic acid bind fat cell PPAR gamma and hepatic PPAR alpha. Both nuclear proteins are phosphorylated through an insulin pathway, thereby inhibiting the expression of genes favoring obesity and stimulating that of genes accelerating fatty acid oxidation. The array of dietetic and pharmacologic tools considered today is analyzed.
Christophe
J
J
Laboratoire de Biochimie générale et humaine, Institut de Pharmacie, Université libre de Bruxelles.
D000273:Adipose Tissue / Q000378:metabolism; D006063:Chorionic Gonadotropin / Q000502:physiology; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects; D005943:Gluconeogenesis; D018149:Glucose Intolerance / Q000378:metabolism; D006801:Humans; D007006:Hypogonadism / Q000378:metabolism; D007027:Hypothalamic Diseases / Q000235:genetics / Q000378:metabolism*; D007030:Hypothalamo-Hypophyseal System / Q000378:metabolism; D009765:Obesity / Q000235:genetics* / Q000378:metabolism*; D010913:Pituitary-Adrenal System / Q000378:metabolism; D011453:Prostaglandins / Q000502:physiology; D014443:Tyrosine / Q000502:physiology
D006063:Chorionic Gonadotropin; D011453:Prostaglandins; D014443:Tyrosine
L'endocrinologie moléculaire des obésités héréditaires.