Impaired thermoregulation in cold-exposed rats with hypothalamic obesity

Abstract

Rats with obesity-producing, hypothalamic knife cuts were fed a high fat diet and placed in the cold (2 °C) for six days starting 3, 11, or 24 days after surgery. Between surgery and cold exposure, knife-cut rats consumed 90% to 122% more energy and gained more weight (32 ± 4, 112 ± 5, and 241 ± 9 g) than sham-operated rats (15 ± 2, 34 ± 2, and 58 ± 3 g). When exposed to cold, sham-operated rats increased (22% to 30%) energy intake whereas knife-cut rats decreased (5% to 51%) intake. After 24 hours at 2 °C body temperatures of knife-cut rats were 1.2, 0.7, and 0.7 degrees less than those of control rats; body temperatures continued to decrease to 2.9, 3.0 and 2.5 degrees less than control rats after six days at 2 °C. Fasting for 12 hours at 2 °C caused a further reduction in body temperature to 4.9, 4.8, and 5.9 degrees less than in control rats. Cold exposure increased urinary excretion of norepinephrine and epinephrine (indicators of sympathoadrenal activity) in all rats. Guanosine diphosphate (GDP) binding to brown adipose tissue (BAT) mitochondria (an indicator of the thermogenic capacity of the tissue) was similar in cold-exposed, knife-cut, and sham-operated rats. Cold acclimation before hypothalamic knife-cut surgery prevented the cold-induced decrease in body temperatures of knife-cut rats. Hypothermia in cold-exposed knife-cut rats was not secondary to the gross obesity that developed in these rats nor did it appear to be a result of reduced sympathoadrenal response to cold or limited thermogenic capacity of BAT. The rapid fall in body temperatures of knife-cut rats during fasting suggests that impaired ability to mobilize lipid reserves for thermoregulation contributes to their hypothermia.