[The regulation of body mass and its relation to the development of obesity].
Body mass--strictly speaking: the adipose tissue mass--is regulated in a feed-back system by the hypothalamus and brainstem, where adiposity signals (leptin, insulin, amylin) and intestinal peptides (ghrelin, PYY, PP, GLP-1, OXM, CCK) and the vagal nerve provide afferent information to the central controller on the size of white adipose tissue and the actual nutritional state, respectively. Two distinct groups of neurons in the arcuate nucleus accept and process the afferent information provided by leptin produced by white adipocytes in proportion to their mass. Leptin binding to the leptin-receptors on the surface of these neurons initiates intracellular signal transduction and activation of target genes, resulting in the synthesis and release of neuropeptides (POMC, CART) with anorectic effects. Secondary centers in the brain are also activated, and finally integrated effector mechanisms are generated in order to regulate the balance between energy intake and expenditure. The regulation of body weight is carried out by the central nervous system in a complex and redundant way, characterized by interconnections and overlaps with other neuroendocrine functions, such as growth, thyroid and adrenal function, memory, addictive and reward mechanisms. Targeting one or another component of this complicated system with drugs might result in interference with other systems and functions, so the occurrence of adverse events is probable. The worldwide epidemic of obesity--resulting mostly from the abundance of energy-dense foods and sedentary lifestyle coupled with a regulatory system unable to cope with this environment--has resulted in a continuous increase of research activities in both academic and industrial centers to develop new drugs and treatment strategies beyond lifestyle changes (diet, physical activity and behavioral therapy) to fight obesity more effectively.
Juhász
Attila
A
Sopron MJV Erzsébet Kórház, a DE OEC Oktató Kórháza Belgyógyászat Sopron Gyori. juhasza@sopkorh.elender.hu
Katona
Evelin
E
Csongrádi
Eva
E
Paragh
György
G
D052436:Adipose Tissue, White / Q000378:metabolism*; D000682:Amyloid / Q000378:metabolism; D000818:Animals; D019440:Anti-Obesity Agents / Q000494:pharmacology; D001066:Appetite / Q000187:drug effects; D001069:Appetite Regulation / Q000187:drug effects; D001823:Body Composition; D015992:Body Mass Index; D001835:Body Weight; D001921:Brain / Q000378:metabolism*; D001933:Brain Stem / Q000378:metabolism; D004435:Eating; D002149:Energy Intake; D004734:Energy Metabolism; D005768:Gastrointestinal Hormones / Q000378:metabolism*; D054439:Ghrelin / Q000378:metabolism; D014943:Global Health; D006801:Humans; D007031:Hypothalamus / Q000378:metabolism; D007328:Insulin / Q000378:metabolism; D058228:Islet Amyloid Polypeptide; D020738:Leptin / Q000378:metabolism; D009419:Nerve Tissue Proteins / Q000378:metabolism; D009490:Neurosecretory Systems / Q000378:metabolism*; D009765:Obesity / Q000188:drug therapy / Q000453:epidemiology / Q000378:metabolism*; D036361:Peptide Hormones / Q000378:metabolism; D011333:Pro-Opiomelanocortin / Q000378:metabolism; D012528:Satiety Response / Q000187:drug effects; D015398:Signal Transduction; D000098882:Cocaine- and Amphetamine-Regulated Transcript Protein
D000682:Amyloid; D019440:Anti-Obesity Agents; D005768:Gastrointestinal Hormones; D054439:Ghrelin; D007328:Insulin; D058228:Islet Amyloid Polypeptide; D020738:Leptin; D009419:Nerve Tissue Proteins; D036361:Peptide Hormones; D000098882:Cocaine- and Amphetamine-Regulated Transcript Protein; D011333:Pro-Opiomelanocortin