Opposite effect of cold on energetic efficiency in normal and obese Wistar rats with hypothalamic lesions.

Reduced thermogenesis in brown adipose tissue (BAT) may contribute to increased energetic efficiency and obesity in rats with ventromedial hypothalamic (VMH) lesions. Thermogenic activity of BAT is a function of the environmental temperature. If a relationship exists, it follows that the increased energetic efficiency of VMH-lesioned rats likewise should be governed by temperature. We have therefore investigated the energy balance of normal and VMH-lesioned rats housed at 30 degrees C and 10 degrees C. Experiments at differing feeding levels allowed calculation of maintenance energy requirements and the net energetic efficiencies of each group. VMH-lesioned rats at thermoneutrality (30 degrees C) accumulated more body fat at all feeding levels than did normal rats. Maintenance energy requirement was reduced, but the net energetic efficiency did not differ significantly from normal. The reduced maintenance energy requirement of lesioned rats persisted at 10 degrees C. Net energetic efficiency decreased in normal rats acclimated to cold but increased in the lesioned group. The difference was significant (P less than 0.05). The cold-induced increase in interscapular brown adipose tissue (IBAT) oxidative capacity of VMH-lesioned rats was only half that of normal rats. Differences in BAT thermogenesis may be the basis for the differing temperature effects on net energetic efficiency.

Early effects of feeding upon hormonal and metabolic alterations in adult rats with ventromedial (VMH) lesions.

The importance of the nutritional state for the development of metabolic alterations after ventromedial hypothalamic (VMH) destructions has been investigated. In the first experiment, groups of fed and 12 hours fasted animals were operated, given an intraperitoneal injection of 3H2O (1 mCi), and left without food until sacrificed 12 hours postoperatively. The lipogenesis in liver and adipose tissue, and the plasma levels of insulin, glucose, urea, free fatty acids (FFA) and triglycerides (TG) were measured. Animals operated in the fed state had increased lipogenesis in parametrial adipose tissue and hypoglycemia compared to their controls, whereas we found no differences between the groups which had been fasted 12 hours before surgery. In the second experiment, animals were deprived of food for 12 hours before being lesioned or sham-operated, and for 12 more hours postoperatively. They were then given one meal by stomach tube, and groups were killed 2, 4, 8 and 12 hours later. The following differences between groups were observed: 2 hours after feeding, the lesioned animals had increased plasma TG levels, but decreased liver lipogenesis. 4 hours after feeding, animals with lesions were hypoglycemic, and had lower plasma levels of FFA and TG than the controls. Hypoglycemia in lesioned animals was found also 8 hours after feeding, together with increased plasma TG levels. 12 hours after feeding, increased liver lipogenesis in lesioned animals was the only difference observed between the groups. The third and last experiment investigated the effect of three meals given 12, 18 and 24 hours postoperatively. Lesioned animals sacrificed 4 hours after the third meal had hypoglycemia, increased plasma TG levels, and increased lipogenesis, both in liver and adipose tissue. The metabolic differences between lesioned and sham-operated animals persisted also 8 hours after the last meal, except for the lipogenesis in adipose tissue. No differences in plasma insulin levels between animals with lesions or sham-operations were observed in these experiments.

Protein depletion and energy retention in rats with ventromedial hypothalamic lesions.

The catabolic effect of bilateral lesions in the ventromedial are of the hypothalamus (VMH) was studied in nitrogen-balance experiments and compared with the effect of a sham-operation in control animals. A transitory (24 h) increase in urine nitrogen was found in the controls, while in the lesioned animals, a persistent increase was found as long as the animals were fed. Fasting (48 h) eliminated the difference in urea excretion between the groups. Food-dependent effects of the VMH lesion are suggested. The changes in body and organ composition of VMH-lesioned animals, kept for 4 months on a food intake close to normal, were studied. The massive increase of body lipids and marked decrease of body protein and water was primarily due to increased subcutaneous-and abdominal-fat, and reduced skeletal and skin protein. An almost normal composition of the liver and close to normal amounts of protein in the viscera demonstrate that at least some tissues in VMH animals are able to maintain a normal protein content. Hyperphagia as a means to counteract the increased amino acid catabolism and to sustain the lean body mass is discussed.

Consequences of ventromedial hypothalamic lesions on metabolism of perfused rat liver.

Metabolism of perfused livers from control and ventromedial hypothalamus (VMH)-lesioned rats has been studied. To eliminate the possibility that observed metabolic abnormalities could be realted to hyperphagia, VMH-lesioned rats were placed on restricted diet matching that of controls. Ten days postoperatively, VMH-lesioned rats had hyperinsulinemia, hypertriglyceridemia, increased blood urea nitrogen levels, together with decreased plasma free fatty acid (FFA) and glucose levels. Insulin release produced in vivo by a glucose load was much higher in VMH-lesioned than in control rats. Perfused livers from VMH-lesioned rats secreted more triglycerides and produced more urea than controls, whereas production of glucose and ketone bodies was reduced. Lipogenesis, newly synthesized triglyceride secretion, and the activity of acetyl-CoA carboxylase and fatty acid synthetase were greatest in livers from VMH-lesioned rats. Fasting abolished hyperinsulinemia and most of these observed metabolic alterations. After treatment with anti-insulin serum, the high rate of lipogenesis observed in livers from VMH-lesioned rats was restored toward normal. It is suggested that hyperinsulinemia may be partly responsible for the metabolic disorders observed in livers from nonhyperphagic VMH-lesioned rats.

The effect of ventromedial hypothalamic lesions on metabolism and insulin secretion in rats on a controlled feeding regimen.

The metabolic effect of ventromedial hypothalamic (VMH) lesions, which are known to cause hyperphagia and obesity, has been studied in rats kept on a controlled light and food regimen. The animals were sacrificed at 4 different times during the second postoperative day. A feeding-induced hypersecretion of insulin was found to the VMH-lesioned animals. It was accompanied by a marked hypoglycemia as compared to the control groups during the feeding period. The glycogen content of liver and diaphragm in the lesioned groups is increased as compared to the controls during the same period. The VMH-lesioned animals showed hypertriglyceridemia both in the fed and fasted state, whereas the postabsorptive plasma levels of free fatty acids and glycerol were decreased. An increased level of urea was observed in all lesioned groups. This is in accordance with the demonstrated protein catabolism which follows VMH lesions.

Increased hepatic triacylglycerol secretion in fasted rats with ventromedial hypothalamic lesions.

Adult female rats with lesions in the ventromedial hypothalamic area and sham-operated controls were given Triton WR 1339 intravenously after 24 h without food for measurement of liver triacylglycerol secretion rate. Tritiated water was injected for measurement of lipogenesis in liver, perirenal and subcutaneous adipose tissues in vivo. The experiments were performed on unrestrained animals with a chronically implnted venous heart cannula after 24 h without food. By the use of this technique, anesthesia and handling of the animals during the experiments was avoided. The following differences in the lesioned animals compared to the sham-operated controls were found: relative hypertriglyceridemia. A significant increase of triacylglycerol accumulation in the plasma. Increased incorporation of 3H FROM 3H20 into liver fatty acids. The experiments demonstrate that hepatic lipid synthesis during fasting is greater in the lesioned than in the control animals, but not high enough to account for the increased triacylglycerol secretion. A shift in the hepatic metabolism of fatty acids, leading to greater triacylglycerol formation at the expense of other processes is therefore suggested. The possible role of insulin in these metabolic changes is discussed.

Protein metabolism in rats with ventromedial hypothalamic lesions: dietary effects on nitrogen retention.

The protein metabolism of rats bearing bilateral lesions in the ventromedial area of hypothalamus (VMH) was studied in nitrogen balance experiments employing high protein and high fat diets. The catabolic effect of VMH destruction was to a great extent counterbalanced by increased protein intake. This indicates that increased amino acid catabolism, rather than impaired mechanisms for protein synthesis, is responsible for the poor nitrogen retention of VMH-lesioned rat fed normal amounts of protein. A trend of increasing nitrogen excretion with increasing dietary fat was found when the caloric intake of VMH-lesioned animals was elevated by substitution of dietary carbohydrates with fat. Persistent liponeogenesis in spite of the high fat intake, is suggested as a possible explanation for this observation.