Failure to demonstrate early metabolic changes in weanling growth-retarded hypophagic rats with lesions in the dorsomedial hypothalamic nuclei

Abstract

Experiment 1: Weanling male rats received bilateral electrolytic lesions in the dorsomedial hypothalamic nuclei (DMNL rats); sham-operated animals served as controls. Rats were killed four hours and three and seven days postoperatively (post-op). Plasma was obtained and epididymal fat pads, diaphragm and liver aliquots were harvested and the in vitro incorporation of U- 14C-glucose into CO 2, glycogen, lipid and saponifiable fatty acids (FAs) were measured. Body weight, carcass lipid and food intake were significantly lower in DMNL rats than in controls. The only significant lesion-induced metabolic changes were hypoglycemia and greater tracer incorporation into epididymal fat pad lipid and diaphragm glycogen. Both DMNL rats and controls showed similar time courses of tracer incorporation into epididymal CO 2 and FAs, diaphragm lipid and liver CO 2, glycogen, lipid and FAs. Lesioned rats also showed more pronounced decreases of tracer incorporation from day 0 to day 3 in epididymal glycogen and lipid and diaphragm CO 2 and glycogen. These data make it appear unlikely that very early deficits in glucose metabolism are the cause of the growth retardation seen in long-term studies with DMNL rats. The data also demonstrate considerable locus specificity, since weanling rats with ventromedial hypothalamic lesions (VMNL rats) in similar short-term studies have shown dramatic alterations in the above parameters. Experiment 2: Weanling DMNL rats and sham-operated rats were injected via tail vein with tritiated water one hour post-op. One hour after the injection they were decapitated. There were no significant differences between DMNL rats and controls in μmoles tritiated water incorporated into total liver, grams liver tissue, mg liver glycogen and ml or mg plasma glucose. These data suggest normal glucogenesis in DMNL rats one hour after lesion production and made it unlikely that the growth retardation in DMNL rats is related to an early defect in this aspect of protein metabolism. By contrast, weanling VMNL rats show enhanced gluconeogenesis four hours after lesion production.