Components of hypothalamic obesity: bipiperidyl-mustard lesions add hyperphagia to monosodium glutamate-induced hyperinsulinemia.
Rats with bilateral electrolytic lesions in the general region of the ventromedial hypothalamic (VMH) nucleus develop hyperinsulinemia, excessive food intake and obesity. Monosodium glutamate (MSG) destroys neurons of the arcuate hypothalamic (AH) nucleus and produces hyperinsulinemic but hypophagic obesity. Bipiperidyl mustard (BPM) primarily destroys VMH neurons, but has produced only a slight obesity even when rats were maintained on high-fat diets. In the present study, rats treated with MSG (AH lesion) were hyperinsulinemic, moderately obese and hypophagic; BPM rats (primarily VMH lesion) were not different from controls when fed standard chow diets. However, MSG/BPM rats (AH + VMH lesion) were hyperinsulinemic, massively obese and hyperphagic. Thus, two components of the electrolytic lesion syndrome previously attributed to VMH damage (hyperinsulinemia and obesity) were reproduced simply by MSG treatment alone. The third component (hyperphagia) occurred only when both AH and VMH were lesioned, suggesting that neurons in both nuclei may perform a satiety function and may be able to substitute for one another in this respect. Since MSG treatment is required for all components of both obesity syndromes described here, this underscores the importance of MSG-sensitive neurons in mechanisms of obesity. The combined treatment approach also represents the first rat model of hyperinsulinemic, hyperphagic obesity that can be entirely produced by systemic administration of neurotoxins.
Scallet
A C
AC
Olney
J W
JW
D000818:Animals; D000831:Animals, Newborn; D004598:Electrosurgery; D001068:Feeding and Eating Disorders / Q000139:chemically induced*; D005260:Female; D005971:Glutamates / Q000633:toxicity*; D006946:Hyperinsulinism / Q000139:chemically induced* / Q000503:physiopathology; D006963:Hyperphagia / Q000139:chemically induced* / Q000378:metabolism; D007031:Hypothalamus / Q000503:physiopathology*; D008297:Male; D009150:Mustard Compounds / Q000633:toxicity*; D009765:Obesity / Q000139:chemically induced* / Q000503:physiopathology; D051381:Rats; D011919:Rats, Inbred Strains; D012970:Sodium Glutamate / Q000633:toxicity*
D005971:Glutamates; D009150:Mustard Compounds; C011680:bipiperidyl mustard; D012970:Sodium Glutamate