2015 Jun 30. doi: 10.1038/nrendo.2015.103. [Epub ahead of print]
Obesity ensues from an imbalance between energy intake and expenditure that results from gene-environment interactions, which favour a positive energy balance. A society that promotes unhealthy food and encourages sedentary lifestyle (that is, an obesogenic environment) has become a major contributory factor in excess fat deposition in individuals predisposed to obesity. Energy homeostasis relies upon control of energy intake as well as expenditure, which is in part determined by the themogenesis of brown adipose tissue and mediated by the sympathetic nervous system. Several areas of the brain that constitute cognitive and autonomic brain systems, which in turn form networks involved in the control of appetite and thermogenesis, also contribute to energy homeostasis. These networks include the dopamine mesolimbic circuit, as well as the opioid, endocannabinoid and melanocortin systems. The activity of these networks is modulated by peripheral factors such as hormones derived from adipose tissue and the gut, which access the brain via the circulation and neuronal signalling pathways to inform the central nervous system about energy balance and nutritional status. In this Review, I focus on the determinants of energy homeostasis that have emerged as prominent factors relevant to obesity.