Leptin regulation of lipid homeostasis: dietary and metabolic implications

Leptin is a 16 kDa protein synthesized and secreted primarily from adipocytes. Leptin acts centrally to regulate appetite and energy expenditure and has peripheral effects to coordinate whole-body energy metabolism. Leptin acts as an energy balance and nutrient sensor; its expression and function are regulated by endocrine and dietary factors. Leptin regulates lipid metabolism, specifically lipid storage in adipocytes as well as in skeletal muscle, liver and the pancreas. Effects of leptin on tissue lipid metabolism include regulation of lipogenesis and fatty acid oxidation. Leptin resistance is a hallmark of rodent and human obesity and appears to be due to defects in leptin-receptor signalling (proximal and perhaps distal) as well as impaired leptin transport into the brain. Dietary composition, especially dietary fatty acid intake and profile, impacts on the expression of genes encoding leptin and leptin receptors as well as downstream leptin effectors. Dietary fat consumption, especially consumption of saturated fatty acids, can induce leptin resistance. Leptin has been implicated in nutritional programming during fetal and neonatal growth with long-term effects on susceptibility to obesity, diabetes and CHD in adults.