Effect of leptin deficiency on metabolic rate in ob/ob mice

Reduced metabolic rate may contribute to weight gain in leptin-deficient (o b/ob) mice; however, available studies have been criticized for referencing O-2 consumption ((V) over dot o(2)) to estimated rather than true lean bod y mass. To evaluate whether leptin deficiency reduces energy expenditure, f our separate experiments were performed: 1) NMR spectroscopy was used to me asure fat and nonfat mass, permitting (V) over dot o(2) to be referenced to true nonfat mass; 2) dietary manipulation was used in an attempt to elimin ate differences in body weight and composition between ob/ob and C57BL/6J m ice; 3) short-term effects of exogenous leptin (0.3 mg kg(-1)day(-1)) on (V ) over dot o(2) were examined; and 4)body weight and composition were compa red in leptin-repleted and pair-fed ob lob animals. ob lob animals had grea ter mass, less lean body mass, and a 10% higher metabolic rate when (V) ove r dot o(2) was referenced to lean mass. Dietary manipulation achieved ident ical body weight in ob/ob and C57BL/6J animals; however, despite weight gai n in C57BL/6J animals, percent fat mass remained higher in ob/ob animals (5 5 vs. 30%). Exogenous leptin increased (V) over dot o(2) in ob/ob but not c ontrol animals. Weight loss in leptin-repleted ob lob mice was greater than in pair-fed animals (45 vs. 17%). We conclude, on the basis of the observe d increase in (V) over dot o(2) and accelerated weight loss seen with lepti n repletion, that leptin deficiency causes a reduction in metabolic rate in ob lob mice. In contrast, these physiological studies suggest that compari son of (V) over dot o(2) in obese and lean animals does not produce useful information on the contribution of leptin to metabolism.