Leptin: an essential regulator of lipid metabolism

This paper reviews the general mechanisms by which leptin acts as a regulat or of lipid reserves through changes in food intake, energy expenditure and fuel selection, with an emphasis on its direct effects on cellular lipid m etabolism. Briefly, when leptin levels increase, food consumption decreases via modulation of hypothalamic neuropeptides. As well, normal decreases in energy expenditures (e.g. with diurnal cycles or reduced caloric intake) d o not occur. This is probably caused by an increase in mitochondrial proton leak mediated by leptin via increases in sympathetic nervous system stimul ation and thyroid hormone release. The decrease in caloric input coupled wi th relatively higher energy expenditure, therefore, leads to negative energ y balance. Leptin also changes the fuel source from which ATP is generated. Fuel preference switches from carbohydrate (glucose) to lipid (fatty acids ). This effect arises through stimulation of triacylglycerol catabolism by leptin. In vitro studies show that leptin is a potent stimulator of lipolys is and fatty acid oxidation in adipocytes and other cell types. Consequentl y, leptin is also a regulator of cellular triacylglycerol content. Hormonal regulation of leptin, as well as its role in fasting and seasonal weight g ain and energy expenditure are also briefly discussed. (C) 2000 Elsevier Sc ience Inc. All rights reserved.