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

Abstract

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 (79 vs 48%, 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 175%) 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.

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Acknowledgements

A Career Development Award from the American Diabetes Association and NIH RO1 DK58855-01 (both to ROD) supported these studies.

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Correspondence to R M O'Doherty.

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O'Doherty, R., Nguyen, L. Blunted fasting-induced decreases in plasma and CSF leptin concentrations in obese rats: the role of increased leptin secretion. Int J Obes 28, 173–175 (2004). https://doi.org/10.1038/sj.ijo.0802477

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