ABSTRACT Direct measurements of heat production were made in 3 to 4 month old lean and obese mice... more ABSTRACT Direct measurements of heat production were made in 3 to 4 month old lean and obese mice during 3 days of fasting and 2 days of refeeding, 6 weeks of dietary restriction, and 2 weeks of thyroxine (T4) administration. Obese mice produced slightly more total heat per animal at this age but weighed 1.5 to 2 times as much as lean mice and consumed more diet ad libitum. Heat production of obese mice was not as responsive to fasting as that of lean mice. When fed equal amounts of diet, obese mice continued to produce at least as much total heat as lean mice. Heat production of obese mice was more sensitive to T4 administration when compared to that of lean mice and unlike the lean mice, T4-treated obese mice were unable to adjust food intake to maintain body weight during a T4-induced increase in thermogenesis. These data suggest that metabolic responses of obese mice to changes in energy intake or output do not occur as rapidly as those of lean mice.
American Journal of Physiology Endocrinology and Metabolism, Aug 1, 1987
Adrenalectomy prevents development of obesity in ob/ob mice fed high-carbohydrate stock diets par... more Adrenalectomy prevents development of obesity in ob/ob mice fed high-carbohydrate stock diets partly by stimulating the low thermogenic capacity of their brown adipose tissue (BAT). Adrenalectomy, however, fails to prevent development of obesity in ob/ob mice fed a high-fat diet. Effects of adrenalectomy on BAT metabolism in ob/ob mice fed a high-fat diet were thus examined. ob/ob mice fed the high-fat diet developed gross obesity despite normal BAT metabolism, as assessed by rates of norepinephrine turnover in BAT, GDP binding to BAT mitochondria, and GDP-inhibitable, chloride-induced mitochondrial swelling. Adrenalectomy failed to arrest the development of obesity or to influence BAT metabolism in ob/ob mice fed the high-fat diet. Development of obesity in ob/ob mice fed a high-fat diet is not associated with low thermogenic capacity of BAT or with adrenal secretions, as it is in ob/ob mice fed high-carbohydrate stock diets.
The possibility that sympathetic nervous system activity, as assessed by measurement of norepinep... more The possibility that sympathetic nervous system activity, as assessed by measurement of norepinephrine turnover, in brown adipose tissue of animals with a predisposition for development of obesity is altered has been examined. Evidence is provided to indicate that ob/ob mice, fa/fa rats and rats with hypothalamic lesions all exhibit some abnormalities of norepinephrine kinetics in brown adipose tissue. Data are needed to evaluate the contribution of these abnormalities to development of obesity in these animals.
American Journal of Physiology Regulatory Integrative and Comparative Physiology, Sep 1, 1999
Leptin inhibits food intake and increases metabolic rates in adult mice. Neonatal mice need to ma... more Leptin inhibits food intake and increases metabolic rates in adult mice. Neonatal mice need to maximize food intake and also maintain high thermoregulatory metabolic rates to optimize survival, suggesting that leptin may function differentially in neonatal versus adult animals. The efficacy of exogenous leptin to alter these two physiological functions during development was thus examined in C57BL/6J lean (+/+ or ob/+) and ob/ob (leptin-deficient) mice. Intraperitoneal leptin administration (1 mg/kg body wt) to lean and ob/ob pups from 7 to 10 days of age did not affect milk intake, oxygen consumption, body weight, or epididymal fat pad weights. Intracerebroventricular injection of 1 microg leptin to 9-day-old pups also failed to influence milk intake or oxygen consumption. Because neither lean nor ob/ob pups responded to exogenous leptin, high endogenous plasma leptin concentrations per se in these lean mice do not explain their resistance to leptin. Leptin administered intracerebroventricularly also failed to alter milk/food intakes of 17-day-old pups but markedly increased oxygen consumption of these older mice. By 28 days of age, intracerebroventricular leptin inhibited food intake. The well-defined actions of leptin to reduce food intake and enhance metabolic rates do not develop synchronously. The ability of leptin to accelerate metabolic rates is acquired early in life and independent of its anorectic action, which may promote survival of neonates.
ABSTRACT Direct measurements of heat production were made in 3 to 4 month old lean and obese mice... more ABSTRACT Direct measurements of heat production were made in 3 to 4 month old lean and obese mice during 3 days of fasting and 2 days of refeeding, 6 weeks of dietary restriction, and 2 weeks of thyroxine (T4) administration. Obese mice produced slightly more total heat per animal at this age but weighed 1.5 to 2 times as much as lean mice and consumed more diet ad libitum. Heat production of obese mice was not as responsive to fasting as that of lean mice. When fed equal amounts of diet, obese mice continued to produce at least as much total heat as lean mice. Heat production of obese mice was more sensitive to T4 administration when compared to that of lean mice and unlike the lean mice, T4-treated obese mice were unable to adjust food intake to maintain body weight during a T4-induced increase in thermogenesis. These data suggest that metabolic responses of obese mice to changes in energy intake or output do not occur as rapidly as those of lean mice.
American Journal of Physiology Endocrinology and Metabolism, Aug 1, 1987
Adrenalectomy prevents development of obesity in ob/ob mice fed high-carbohydrate stock diets par... more Adrenalectomy prevents development of obesity in ob/ob mice fed high-carbohydrate stock diets partly by stimulating the low thermogenic capacity of their brown adipose tissue (BAT). Adrenalectomy, however, fails to prevent development of obesity in ob/ob mice fed a high-fat diet. Effects of adrenalectomy on BAT metabolism in ob/ob mice fed a high-fat diet were thus examined. ob/ob mice fed the high-fat diet developed gross obesity despite normal BAT metabolism, as assessed by rates of norepinephrine turnover in BAT, GDP binding to BAT mitochondria, and GDP-inhibitable, chloride-induced mitochondrial swelling. Adrenalectomy failed to arrest the development of obesity or to influence BAT metabolism in ob/ob mice fed the high-fat diet. Development of obesity in ob/ob mice fed a high-fat diet is not associated with low thermogenic capacity of BAT or with adrenal secretions, as it is in ob/ob mice fed high-carbohydrate stock diets.
The possibility that sympathetic nervous system activity, as assessed by measurement of norepinep... more The possibility that sympathetic nervous system activity, as assessed by measurement of norepinephrine turnover, in brown adipose tissue of animals with a predisposition for development of obesity is altered has been examined. Evidence is provided to indicate that ob/ob mice, fa/fa rats and rats with hypothalamic lesions all exhibit some abnormalities of norepinephrine kinetics in brown adipose tissue. Data are needed to evaluate the contribution of these abnormalities to development of obesity in these animals.
American Journal of Physiology Regulatory Integrative and Comparative Physiology, Sep 1, 1999
Leptin inhibits food intake and increases metabolic rates in adult mice. Neonatal mice need to ma... more Leptin inhibits food intake and increases metabolic rates in adult mice. Neonatal mice need to maximize food intake and also maintain high thermoregulatory metabolic rates to optimize survival, suggesting that leptin may function differentially in neonatal versus adult animals. The efficacy of exogenous leptin to alter these two physiological functions during development was thus examined in C57BL/6J lean (+/+ or ob/+) and ob/ob (leptin-deficient) mice. Intraperitoneal leptin administration (1 mg/kg body wt) to lean and ob/ob pups from 7 to 10 days of age did not affect milk intake, oxygen consumption, body weight, or epididymal fat pad weights. Intracerebroventricular injection of 1 microg leptin to 9-day-old pups also failed to influence milk intake or oxygen consumption. Because neither lean nor ob/ob pups responded to exogenous leptin, high endogenous plasma leptin concentrations per se in these lean mice do not explain their resistance to leptin. Leptin administered intracerebroventricularly also failed to alter milk/food intakes of 17-day-old pups but markedly increased oxygen consumption of these older mice. By 28 days of age, intracerebroventricular leptin inhibited food intake. The well-defined actions of leptin to reduce food intake and enhance metabolic rates do not develop synchronously. The ability of leptin to accelerate metabolic rates is acquired early in life and independent of its anorectic action, which may promote survival of neonates.
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