Roseline Bertin

Hormonal Stimulation of Substrate Utilization in Brown Adipose Tissue of Cold Acclimated Rats

Summary A study of glucose, glycerol and free fatty acid (FFA) uptake and release in the interscapular brown adipose tissue (BAT) was done on rats acclimated to constant cold (CA), fluctuating cold (Cy) or a control ambient temperature. At thermal neutrality the arteriovenous differences and the blood flow through the tissue were estimated. The effects of norepinephrine (NE) or dibutyryl cyclic-AMP (DBcAMP) were measured. Before infusions an uptake of plasma FFA by BAT was found in CA and Cy rats, and there was a release in the controls. Plasma glucose was taken up by the BAT of the three groups of rats. DBcAMP infusions did not enhance blood flow and lipid metabolism in BAT but increased glucose uptake in all the groups. By the end of a NE infusion, blood flow was increased 2.4-fold in controls and four- to fivefold in CA and Cy rats. Glucose uptake and glycerol release were greatly increased in all the groups. In controls hydrolyzed fatty acids were released in the venous blood, but in CA and Cy rats most of them were retained in the tissue. Therefore, in the controls BAT seems to be essentially a reserve of lipids which can be mobilized by NE. In the two groups of cold acclimated animals, the fatty acids hydrolyzed by NE, which are retained in the tissue, may be the substrate of the NE dependent increase of tissue energetic metabolism.

Glycerokinase activity and lipolysis regulation in brown adipose tissue of cold acclimated rats.

Glycerol release by brown adipocytes from constant cold adapted rats was not stimulated by norepinephrine. On the contrary, the release was stimulated in rats adapted to a nycthemeral fluctuatiing temperature from 5 degrees to 28 degrees C. Glycerokinase activity was greatly increased in brown adipose tissue by cold adptation ; there was no change in the liver. However this increased activity cannot entirely explain the lack of norepinephrine stimulation of glycerol release in the brown adipose tissue of cold adapted rats.

Effects of cold acclimation on the feeding pattern and energetic metabolism of genetically obese Zucker rats.

1. The feeding pattern, growth rate and energetic metabolism were studied in obese Zucker rats of 5-12 weeks of age kept at ambient temperatures of 22 or 10 degrees C. 2. During this period, the increment in obesity of the 22 degrees C-exposed animal was found to be due to diurnal hyperphagia and not to a lowered resting metabolism. 3. In the 10 degrees C-exposed rat the development of non-shivering thermogenesis associated with a lack of enhancement of food intake leads to prevent the obesity.

Effects of diets and cold acclimation on lipoprotein lipase activity and cyclic nucleotide levels in some tissues of rats.

In view to study a possible regulation of lipoprotein lipase (LPL) activity by tissue cyclic nucleotide levels (cAMP and cGMP), parallel determinations of the three factors were performed on brown adipose tissue (BAT), epidymal fat (WAT) and heart of rats. Opposite variations of cAMP levels and LPL activity were only observed in WAT following high fat diet administration. The enhancement of LPL activity in BAT and in heart by cold acclimation or feeding an hyperlipidic diet was never associated with a decrease in cAMP content. The variations of cAMP and cGMP levels were not dependent. It is concluded that there is no effect of cyclic nucleotide levels in the enhancement of LPL activity in these tissues.

Metabolic changes associated with sustained 48-Hr shivering thermogenesis in the newborn pig

Metabolic changes associated with sustained 48-hr shivering thermogenesis were studied in piglets maintained at 34 (thermoneutrality) or 25 degrees C (cold) between 6 and 54 hr of life. Despite their high shivering activity and elevated heat production, cold-exposed piglets exhibited a slightly lower rectal temperature than thermoneutral animals (-1.1 degrees C; P < 0.01) at the end of the treatment. The enhancement of heat production and shivering activity were associated with a decrease in muscle glycogen (-47%; P < 0.05) and total lipid content (-23%; P < 0.05), a reduction of blood lactate levels (P < 0.05) and an enhancement of muscle cytochrome oxidase activity (+20%; P < 0.05) which suggests that muscle oxidative potential was increased by cold exposure. Potential for capturing lipids (lipoprotein lipase activity) was also higher in the red rhomboideus muscle (+71%; P < 0.01) and lower in adipose tissue (-58%; P < 0.01) of the cold-exposed piglets. Measurements performed at the mitochondrial level show no changes in rhomboideus muscle, but respiratory capacities (state IV and FCCP-stimulated respiration) and intermyofibrillar mitochondria oxidative and phosphorylative (creatine kinase activity) capacities were enhanced in longissimus dorsi muscle (P < 0.05). These changes may contribute to provide muscles with nonlimiting amount of readily oxidable substrates and ATP necessary for shivering thermogenesis. A rise in plasma norepinephrine levels was also observed during the second day of cold exposure (P < 0.05).

Effects of cold acclimation on the activity of lipoprotein lipase in adipose tissues of genetically obese Zucker rats

The activity of lipoprotein lipase (LPL) was studied in interscapilar brown adipose tissue (BAT), epididymal white adipose tissue (WAT) and in the heart of lean and obese adult Zucker rats maintained at 22 degrees C or adapted to cold (10 degrees C). In WAT the specific activity per gram of tissue was lower in obese than in lean rats but the total activity within the tissue was three-fold higher. Cold acclimation did not modify total activity in either lean or obese rats. In BAT, but not in the heart, both specific and total activities were lower in obese than in lean animals. They were enhanced in both tissues following cold acclimation. Six-hour fasting led to a decrease in specific activity in WAT of lean rats but had no effect in obese animals; an increase was observed in BAT and heart of both genotypes. Insulin administration has no effect on activities in WAT in either 22 or 10 degrees C adapted obese rats. Norepinephrine administration stimulates LPL activity in BAT and heart of all groups. It is concluded that the lack of development of obesity previously observed in obese rats following cold acclimation is not due to a decreased capacity of lipid uptake by WAT. It might in part be due to an increased lipid oxidation in BAT.

Evidence for a cold-induced aldosterone stimulation in the rat

This study was undertaken to determine the secretion of aldosterone by male Long-Evans rats acclimated for six weeks to moderate cold (15 C), in comparison with rats maintained at thermo-neutral temperature (28 C). The following determinations were made: corticosteroids in plasma and adrenals, PRA, and hydromineral balance. Cold acclimation highly increased the plasma and adrenal levels of aldosterone and corticosterone. The cold stimulation of aldosterone was induced neither by the renin-angiotensin system, nor by alterations of hydromineral balance: PRA, plasma sodium and potassium concentrations, blood hematocrit, and hydromineral balance at 15 C and 28 C did not differ. Moreover this stimulation was induced neither by ACTH, nor by any other hypophyseal factors, since plasma aldosterone levels remained high in hypophysectomized rats. This study provides evidence of an aldosterone stimulation which appeared during moderate cold acclimation; the origin of this stimulation must be investigated.

Prostaglandins E2 and Fα levels in white and brown adipose tissues of cold acclimated rats as measured by a new micromethod

A new micro-method was used to determine the effects of cold acclimation of rats on the levels of prostaglandin E2 and F alpha in both white and brown adipose tissues. Whereas PGF alpha levels were significantly higher than PGE2 levels in white fat, no difference between the amounts of the two prostaglandins was observed in brown fat. In both tissues, cold acclimation did not induce any change in prostaglandin levels.

Glycerokinase activity in brown and white adipose tissues of cold-adapted obese Zucker rats

Glycerokinase activity was measured in the brown and white adipose tissues compared with that in the liver obese Zucker rats adapted or not adapted to cold. In white adipose tissue total activity was low but higher in the fa/fa rats than in the Fa/ones; cold adaptation did not modify this activity. In brown adipose tissue specific activity was higher than in white; specific activity was twice as high in the fa/fa rats than in the Fa/-. Cold-adaptation induced an increase in the activity in the Fa rats and a decrease in the fa/fa rats. The results are discussed with regard to the cold-induced increase in the energetic efficiency of the tissue.

Catecholamine turnover in heart and adrenals of young rats : effects of rearing temperature

1. A comparative chronological study (from birth to one month of age) was performed to establish the levels and turnover rates of catecholamines in the heart and adrenals of rats born and reared at 28 and 16 degrees C. 2. In the heart, cold induced marked increases of the norepinephrine level and turnover rate only from the second week of age. 3. In the adrenals there was considerable early stimulation of epinephrine production, but only in 28 degrees C rats. 4. The differences observed in the stimulation of the sympathetic nervous system according to the rearing temperature are possibly due to the behavior of the mother in warming the pups.