Effects of amylin on food intake and body weight via sympathetic innervation of the interscapular brown adipose tissue.

Objective

Amylin acts on the lateral dorsal tegmental nucleus (LDT), resulting in anorexic and weight-loss effects and activates thermogenesis in the interscapular brown adipose tissue (IBAT). In addition, it induces neuronal nitric oxide synthase (nNOS) and choline acetyltransferase (ChAT)-mediated feeding. However, the influence of the intact sympathetic nervous system (SNS) in mediating amylin's effects has not been fully characterised. We investigated whether extracellular signal-regulated kinase (ERK), nNOS, and ChAT activities in the LDT are responsible for amylin's anorexigenic effects and whether this requires an intact SNS.

Methods

C57BL/6J mice [wild-type (WT), sham, and sympathetic denervation of IBAT] were used. Food consumption, body weight, and distribution of pERK, nNOS, and ChAT positive neurons in the brain were examined following acute and chronic amylin administration.

Results

Food intake was significantly decreased in WT and sham animals following acute amylin injection, but not in the denervated mice. Chronic amylin reduced body weight and serum glucose levels after 6 weeks, but increased insulin levels; no changes were observed in the denervated mice. Acute amylin increased the expression of nNOS, ChAT, and uncoupling protein-1 in the IBAT of WT and sham mice, while no changes were observed in the denervated mice and pERK from the above effect.

Conclusions

Intact SNS of IBAT influences amylin-induced suppression of food intake and body weight, thus affecting nNOS and ChAT signalling in the LDT and locus coeruleus.