Blunted fasting-induced decreases in plasma and CSF leptin concentrations in obese rats: the role of increased leptin secretion

Fasting substantially decreases plasma leptin concentration. However, in obesity, the fasting-induced decrease in leptin concentration is blunted or absent. The objective of the current study was to determine in diet-induced obese (DIO) rats the contribution of altered leptin secretion and leptin expression to the blunted nutritional regulation of leptin concentration. Fasting-induced decreases in plasma leptin concentration were greater in lean ( standard chow (SC)) rats compared to DIO (similar to79 vs similar to48%, P<0.05 for DIO vs SC). CSF leptin was significantly reduced by fasting in SC (∼46%) but not in DIO. Fasting decreased adipose tissue leptin secretion in both SC and DIO, but the decrease was greater in SC ( average ∼74%) compared to DIO ( average ∼44%, P<0.05, DIO vs SC). Additionally, leptin secretion in fasted DIO was substantially greater ( average similar to175%) than in fasted SC (P<0.05). Adipose tissue leptin protein content was increased by ∼80% in DIO compared to SC (P<0.05). We conclude that a probable cause of blunted fasting-induced decreases in leptin concentration in obesity is elevated leptin secretion, which possibly results from increased leptin gene expression.