Leptin and intermediary metabolism: Focus on glucoregulation and lipids

Abstract

In the first studies of leptin administration to obese mice it was noted that low dose leptin, which did not alter food intake or body weight, decreased blood glucose. This observation initiated investigation into the mechanisms through which leptin regulated intermediary metabolism independent of effects on caloric intake and body weight. With leptin receptors present in the central nervous system and on peripheral tissues, metabolic effects of leptin can be mediated via activation of neural pathways in the brain or by direct binding to the major metabolic tissues including the liver, skeletal muscle, adipose tissue, and pancreas. Leptin regulation of glucose and lipid homeostasis has been observed in multiple rodent models and in humans with hypoleptinemic lipodystrophy. Understanding the mechanisms through which leptin regulates intermediary metabolism is anticipated to result in better therapeutic interventions to correct dysregulated metabolism in obesity and diabetes.