Hypothalamic and genetic obesity: an appraisal of the autonomic hypothesis and the endocrine hypothesis.
Several lines of evidence support the hypothesis that derangements in the function of the autonomic nervous system play an important role in the development of hypothalamic obesity. Vagotomy below the diaphragm reverses the syndrome. In diabetic rats cured of their diabetes with transplants of fetal pancreatic tissue beneath the renal capsule, ventromedial hypothalamic (VMH) lesions do not produce the characteristic rise in food intake nor do they significantly increase serum insulin. These observations indicate that the hyperinsulinaemia following VMH lesions is the result of neural connections rather than from a circulating humoral factor released following VMH injury. The smaller salivary glands, reduced level of glucagon and impaired mobilization of fatty acids during stress in VMH lesioned rats point to reduced activity of the sympathetic nervous system. The impaired mobilization of fat from retroperitoneal depots in VMH lesioned rats during fasting is similar to the effect of sympathetic denervation of the retroperitoneal fat pad. The turnover of norepinephrine in tissues innervated by the sympathetic nervous system is either reduced or less responsive to nutritional influences after VMH lesions. The thermogenic activity of brown adipose tissue is also impaired after VMH lesions, presumably as a result of reduced sympathetic firing rate of nerves innervating the BAT. In contrast to the reduced activity of the sympathetic nervous system after Vmh lesions there is increased activity after electrolytic lesions of the lateral hypothalamus. Collectively these data indicate that the autonomic nervous system plays a central role in the regulation of metabolic functions following disturbances of hypothalamic function. The concept of the thrifty gene as a mechanism for the development of obesity has been explored in several models. The efficiency with which food is stored as fat appears to be increased in all forms of experimental obesity. Studies in the genetically obese mouse have documented this phenomenon most elegantly. In one experiment animals carrying a double dose of the gene for obesity received exactly the same quality of food on exactly the same schedule throughout a 24 hour period of time as their lean littermates yet gained more body weight and more fat. In a second experiment the importance of a thrifty gene was documented by comparing the rates of weight loss and survival time in homozygous and heterozygous lean animals. Heterozygosity improved survival compared to the homozygous lean animal indicating the value of the genetic trait for survival in the wild.(ABSTRACT TRUNCATED AT 400 WORDS)
D002001:Adipose Tissue, Brown / Q000503:physiopathology; D000315:Adrenalectomy; D000818:Animals; D001341:Autonomic Nervous System / Q000503:physiopathology*; D001833:Body Temperature Regulation; D001921:Brain / Q000502:physiology; D004702:Endocrine Glands / Q000503:physiopathology*; D005838:Genotype; D007031:Hypothalamus / Q000503:physiopathology*; D051379:Mice; D008820:Mice, Obese / Q000235:genetics; D009765:Obesity / Q000235:genetics / Q000503:physiopathology*; D009929:Organ Size; D051381:Rats; D014697:Ventromedial Hypothalamic Nucleus / Q000503:physiopathology