Signalling in body-weight homeostasis: neuroendocrine efferent signals

Whilst a number of neuroendocrine afferent signals are implicated in body-w eight homeostasis, the major efferent pathway is the sympathetic nervous sy stem (SNS), which affects both energy expenditure and substrate utilization . Thyroid hormones and their interactions with the SNS may also have a role to play. Some of the variability in resting energy expenditure can be expl ained by differences in SNS activity, and beta-blockade can reduce energy e xpenditure and diet-induced thermogenesis in Caucasians. Excess energy inta ke leads to SNS activation and increased diet-induced thermogenesis. A rela tionship has also been demonstrated between spontaneous physical activity a nd SNS activity. In many animal models the SNS activates brown adipose tiss ue thermogenesis, hence increasing diet-induced thermogenesis and dissipati ng excess energy as heat. This effect is mediated via beta(3)-adrenoceptors and activation of an uncoupling protein unique to brown adipose tissue. Ho mologous proteins have been identified in human tissues and may play a role in human energy expenditure. How the SNS is implicated in this process is unclear at present. beta(3)-Adrenoceptor polymorphism has been associated b oth with lower resting energy expenditure in some populations and with redu ced autonomic nervous system activity. SNS effects on substrate cycling may also play a role. In the development of obesity the effects of the SNS in promoting lipolysis and fat oxidation are likely to be at least as importan t as its effects on thermogenesis. beta-Blockade has relatively small effec ts on energy expenditure, but more pronounced effects on reducing Lipid oxi dation, so tending to favour fat storage and weight gain. Low lipid oxidati on is a risk factor for weight gain, and there is some evidence that low ba sal sympathetic nerve activity in muscle is associated with this process. O verall, the relationship between SNS activity and obesity is complex, with evidence of low SNS activity occurring in some, but not all, studies.