Brown Adipose Tissue Of Cold-acclimated Rats Research Articles

Basic fibroblast growth factor (bFGF) contributes to the enlargement of brown adipose tissue during cold acclimation.

The contribution of basic fibroblast growth factor to brown adipose tissue (BAT) enlargement during cold acclimation was investigated using rat brown adipocytes in primary culture. After cold exposure (at 5 degrees C) for 28 days, the level of bFGF messenger ribonucleic acid (mRNA) in BAT of cold-acclimated rats was markedly increased with the increase in the BAT weight. In addition, the blood plasma from cold-acclimated rats considerably enhanced the expression of basic fibroblast growth factor mRNA in rat brown adipocytes. Likewise, the blood plasma from cold-acclimated rats significantly stimulated the growth of rat brown adipocyte precursor cells compared with that from warm-acclimated rats, whereas there was no difference of effect between the two blood plasmas on the growth of bovine capillary endothelial cells. Basic fibroblast growth factor, but not platelet-derived growth factor stimulated the growth of brown adipocyte precursor cells. The conditioned medium from brown adipocyte primary culture markedly stimulated the growth of bovine capillary endothelial cells and the effect was inhibited considerably by antibasic fibroblast growth factor antibody. These results suggest that some factors concerned with the growth of brown adipocyte precursor cells are present in the blood plasma from cold-acclimated rats, and that basic fibroblast growth factor produced by brown adipocytes may significantly contribute to BAT enlargement by autocrine mechanisms during cold exposure.

Sympathetic and sensory nerves in control of growth of brown adipose tissue: Effects of denervation and of capsaicin

The thermogenic function and growth of brown adipose tissue (BAT) are known to be primarily under the control of the sympathetic nervous system. However, BAT also contains nerves containing neuropeptides such as substance P (SP) and calcitonin gene-related peptide (CGRP) that are presumed to be sensory nerves. In a previous study we demonstrated an atrophy of BAT in capsaicin-desensitized (CAP-DES) rats. CAP-DES is known to bring about long-lasting impairment of a subpopulation of sensory nerves involved in nociception and characterized by the presence of SP and CGRP. The principal objectives of the present experiments were to find out whether CAP-DES of rats depleted BAT of its sensory neuropeptide, CGRP, whether CAP-DES impaired the sympathetic innervation of BAT and whether the atrophy of BAT induced by CAP-DES resembled that induced by sympathetic denervation. CAP-DES rats had a normal noradrenaline content in BAT (measured by HPLC) but absent CGRP (measured by immunohistochemistry). In CAP-DES rats living at 26 degrees C, BAT had lost 90% of its uncoupling protein (UCP) and 50% of its total protein; its thyroxine 5?-deiodinase (T5?D) concentration was, however, unaltered. Surgical denervation, in contrast, which did not abolish CGRP immunofluorescence in BAT, did not significantly reduce protein or UCP content. Cold-acclimation for 12 days produced large increases in protein and UCP content and T5?D level in intact BAT of control rats. These increases still occurred, although to a lower level, in CAP-DES rats but did not occur surgically denervated BAT. The combination of CAP-DES and surgical denervation resulted in an undetectable level of UCP in BAT of cold-acclimated rats, less than in denervated BAT of control cold-acclimated rats. We conclude that sensory nerves play a role in maintenance of BAT in a warm environment and in cold-induced growth of BAT. This role may be either a trophic effect on mitochondriogenesis or a repressive effect on mitochondrial destruction.

3′:5′-Cyclic-AMP Phosphodiesterase Activities in White and Brown Adipose Tissues of Cold-Acclimated Rats

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.