Recent advances in obesity: adiposity signaling and fat metabolism in energy homeostasis.

Interactions between our conserved 'thrifty genotype' and current trends toward reduced physical activity and increased food intake are posited as the root cause of the rising prevalence of obesity in the modern era. The past decade has seen tremendous advances in our understanding of the physiological regulation of energy balance and adiposity, and important insights into the pathogenesis of obesity. We have gained a more comprehensive view of the energy homeostasis system from the discovery of the adiposity hormone leptin, the subsequent identification of hypothalamic and other brain neuropeptide systems controlling energy balance, and the progress in understanding the molecular mechanisms by which cells can sense and respond to changes in metabolic state. Numerous targets have been identified for potential pharmacological and genetic approaches to obesity management. Some of the most recent developments are prototypic compounds that manipulate fat metabolism, both in peripheral tissues and in the brain, to reduce body fat synthesis and storage and to increase fat oxidation, to reduce food intake, and to increase energy expenditure.