Is leptin the parabiotic "satiety" factor? Past and present interpretations.
In 1959 Hervey hypothesized that a circulating feedback signal informed the hypothalamus of the size of fat stores and initiated appropriate corrections to energy balance. The hypothesis resulted from a parabiosis study in which one animal became obese following lesioning of the ventromedial hypothalamus. The partner of the lesioned rat was hypophagic and lost a large amount of body fat. Similar results came from parabiosis studies with obese Zucker rats and rats that overate due to stimulation of the lateral hypothalamus. In studies in which one parabiont was made obese by overfeeding the non-overfed partners lost substantial amounts of fat with a minimal reduction in food intake and no loss of lean tissue. The loss of fat was due to inhibition of adipose lipogenesis and other metabolic adjustments typical of food restriction. Parabiosis with genetically obese mice implied that ob/ob mice did not produce the feedback signal and subsequently the mutant ob protein, leptin, was identified. This paper provides a review and interpretation of parabiosis work that preceded the discovery of leptin, an evaluation of leptin in relation to its function as the circulating feedback signal and evidence for additional circulating factors involved in the control of adipose tissue mass.
Department of Physiology, Georgia Health Sciences University, 1120 15th Street, Augusta, GA 30912, USA. ruharris@georgiahealth.edu
Ruth B S
RB
Harris
D000273:Adipose Tissue / Q000378:metabolism; D000818:Animals; D001835:Body Weight; D004435:Eating / Q000502:physiology; D004734:Energy Metabolism; D049673:History, 20th Century; D049674:History, 21st Century; D006801:Humans; D007031:Hypothalamus / Q000378:metabolism; D020738:Leptin / Q000097:blood*; D051379:Mice; D008820:Mice, Obese; D052756:Nutritional Sciences / Q000266:history; D009765:Obesity / Q000097:blood / Q000517:prevention & control; D010227:Parabiosis; D051381:Rats; D011924:Rats, Zucker; D012527:Satiation
D020738:Leptin