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.