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This study was designed to investigate the effect of chronic cold exposure (12 degrees C for 3 weeks) on catecholamine production and noradrenaline-induced lipolytic rate to further describe thermoregulatory mechanisms in 5- to 8-week-old pigs. Lipolytic activity in white adipose tissue was assessed in vitro while catecholamine production was estimated by measuring noradrenaline, adrenaline, and dopamine levels in 24-h urine samples. Animals were fed ad libitum and food intake was 20% greater in the cold. In control piglets maintained in a 23 degrees C environment, the addition of increasing amounts of noradrenaline (10(-6), 10(-5), 10(-4) M) stimulates lipolysis (p less than 0.05) and enhances the basal lipolytic rate (5.4 mu equiv. fatty acids.120 min-1.g-1 tissue) by 2.5-, 2.7-, and 3.9-fold, respectively. Three weeks of cold acclimation had no effect on basal lipolytic rate but increased significantly noradrenaline responsiveness: incubation of subcutaneous white fat in the presence of 10(-4) M noradrenaline does increase the basal lipolytic rate by sixfold. Noradrenaline effects were maximally activated by theophylline. Daily dopamine and noradrenaline excretions (3-10 micrograms/24 h) were increased significantly (up to eightfold) after 10 days of cold acclimation. By contrast, adrenaline excretion was quite low (0.6-1.6 micrograms/24 h) and showed no significant variation with time. It is likely that these hormonal and biochemical modifications play a prominent part in the mechanism of cold acclimation in the piglet. Their significance in the development of shivering and nonshivering thermogenesis is discussed in relation to the supply of energy substrates to the fatty acid utilizing tissues and to the possible uncoupling effect of free fatty acids.

Brown adipose tissue (BAT) has an important role in the thermogenesis of newborn mammals and cold-acclimated rodents. Heat production within the tissue is regulated by the sympathetic nervous system (SNS) via norepinephrine (NE) release. As only little is known of the progressive role of SNS during the developmental period, NE content and turnover were determined in BAT of infant rats 1-33 days of age. The dams and the pups were kept at either 28 or 16 degrees C. It was observed that the NE level in the tissue and the mediator turnover had an almost parallel evolution during the experimental period. In the first week of life, level and turnover of NE were higher in the 28 degrees C group than in the 16 degrees C group. During the second week, the level remained constant in rats kept at 28 degrees C, but the NE turnover slightly decreased. In contrast, a large increase of both parameters was observed in rats kept at 16 degrees C. Then a decrease occurred in both groups until weaning. Subsequently the values remained almost constant. It must be noted that, from the end of the first week, NE content and turnover were always significantly higher in the 16 degrees C group than in the 28 degrees C group. At the end of the first month, the level was 50% higher in cold-acclimated rats and turnover was four times as high as in controls.(ABSTRACT TRUNCATED AT 250 WORDS)

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.

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.

The variation in the amounts of cyclic AMP and cyclic GMP were studied in white and brown adipose tissues and in the liver of rats during the first week of cold exposure (5 degrees C). In white fat, only a small increase in cAMP was observed on the first day. In brown fat, parallel decreases in cAMP and cGMP contents were induced which might be related to a large mobilization of tissue fatty acids. In the liver, cold exposure barely affected the cAMP content but the level of cGMP was markedly increased. These results are discussed with regard to the respective role of these different tissues in cold-induced energetic substrate mobilization.

3':5'-Cyclic-AMP phosphodiesterase (PDE) (EC 3.1.4.17) activity was measured in interscapular brown adipose tissue (BAT) and in white epididymal adipose tissue of rats acclimated to constant or fluctuating cold. Experiments were carried out on isolated adipocytes or tissue homogenates. In brown or white adipose tissue or isolated adipocyte homogenates, two different apparent Km values were found according to the substrate (cAMP) concentration. The low Km was at about 10(-6) M and the high one at about 10(-4) M. The apparent V of the high Km enzyme was about 10-fold higher than the V of the low Km enzyme. Cold acclimation to constant or fluctuating cold did not modify appreciably the Km or V values. For low substrate concentrations (10(-6)-10(-8) M), the specific activity of PDE expressed per milligram of protein was decreased in BAT adipocytes of the two groups of cold-acclimated rats, compared to controls. Inversely, it was increased in total tissue homogenates. These variations were smaller in fluctuating cold than in constant cold-acclimate rats. They could, in part, induce the increases in lipolysis and in blood flow observed in the BAT of cold-acclimated rats.

The intracellular level of adenosine 3':5'-monophosphate (cyclic AMP) and its stimulation in vitro by norepinephrine were studied in brown and white adipocytes from rats adapted to constant or fluctuating cold. Cold acclimatization had no effect on the basal cyclic AMP intracellular content in both tissues, but the level in brown adipocytes was four-fold higher than in the white ones. Addition of norepinephrine in the incubation medium doubled the cyclic AMP content of white adipocytes from control or fluctuating-cold-adapted rats, and enhanced four-fold in constant-cold-adapted rats. In brown adipocytes norepinephrine increased cyclic AMP levels in the first two groups, but had no effects in constant-cold-adapted rats. In the two tissues of control and fluctuating-cold-adapted rats the norepinephrine action was increased by phentolamine and decreased by propranolol. The lack of response to norepinephrine of brown adipocytes from constant cold-adapted rats was not due to the predominance of the alpha component of hormone receptors. Antilipolytic drugs (nicotinic acid, insulin and prostaglandin E2) inhibited the action of norepinephrine on white adipocytes; only prostaglandin E2 had an effect on brown ones.

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.