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

Abstract

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.