Components of hypothalamic obesity: bipiperidyl-mustard lesions add hyperphagia to monosodium glutamate-induced hyperinsulinemia

doi:10.1016/0006-8993(86)90434-8

Brain Research

Volume 374, Issue 2, 28 May 1986, Pages 380-384

https://doi.org/10.1016/0006-8993(86)90434-8 Get rights and content

Abstract

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.

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Moreover, anti-inflammatory interleukin 10 (IL10), derived from the spleen, has a critical role in adipocyte function and IR [10,11]. Treatment of neonatal with monosodium L glutamate (MSG) induces hypothalamic lesions that culminate in excessive expansion of WAT, IR, glucose intolerance, dyslipidemia and cardiovascular dysfunctions [8,16–18]. Moreover, MSG-obese rats present alterations in the immunological system, including reduced plasma levels of IL10, a pro-inflammatory state in the WAT and histological abnormalities in the spleen [19].
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Components of hypothalamic obesity: bipiperidyl-mustard lesions add hyperphagia to monosodium glutamate-induced hyperinsulinemia

Abstract

Brain Research

Prediction of carcass fat, water and lean body mass from Lee's ‘Nutritive ratio’ in rats with hypothalamic obesity

Experientia

Effect of hypothalamic lesions at different loci on development of hyperinsulinemia and obesity in the weanling rat

J. Comp. Neurol.

Hypothalamic and genetic obesity in experimental animals: an autonomic and endocrine hypothesis

Physiol. Rev.

Mechanisms of the development of obesity in animals with hypothalamic lesions

Physiol. Rev.

A study of the effect of limitation of food intake and the method of feeding on the rate of weight gain during hypothalamic obesity in the albino rat

Am. J. Physiol.

Detection of treatment effects when only a portion of subjects respond

Concepts and Methods of Experimental Statistics

Hypothalamic obesity in weanling rats

Am. J. Physiol.

Hypothalamic lesions and adiposity in the rat

Anat. Rec.