Role of sensory nerves in growth and thermogenesis of brown adipose tissue.

Abstract

The original objective of work described in this thesis was to study neural control of diet-induced thermogenesis in BAT. The hypothesis was that impairment of central warmth perception by capsaicin-desensitization (CAP-DES) would diminish central suppression of BAT thermogenesis by heat generated as a consequence of food ingestion, and thus enhance sympathetic-mediated diet-induced hypertrophy of BAT. Unexpectedly, CAP-DES caused atrophy of BAT and prevented diet-induced thermogenesis in BAT. This novel finding led to a modification of objectives to find out why CAP-DES induces atrophy of BAT and to study further the consequences for the CAP-DES rat of the atrophied state of its BAT. Atrophy of BAT in the CAP-DES rat involved loss of total protein, loss of mitochondrial proteins and loss of cells. BAT of the CAP-DES rat was unresponsive to stimulation by diet and cold-induced growth was retarded. The most extensive destruction of BAT occurred at 1 day, gradually reversed over the next 28 days, then reappeared at 8 months. A preliminary study in which a neurotransmitter of sensory nerves, calcitonin gene-related peptide (CGRP) was infused for several days suggested that the effect of CAP-DES might be due to removal of a trophic influence of neuropeptides of sensory nerves, known to be depleted in BAT of the CAP-DES rat. The association between atrophied BAT and obesity in several different animal models suggested that CAP-DES rats might become obese. However, CAP-DES rats fed an obesity-inducing diet (high fat) for 10 weeks did not become any more obese than control rats eating the same diet and aging-induced obesity was reduced in the CAP-DES rat. Conclusions. Neuropeptides of sensory nerves play an important role in control of BAT thermogenic capacity, supplementing that of noradrenaline. The relation of atrophied BAT to energy balance in the CAP-DES rat remains to be elucidated.