Leptin alters energy intake and fat mass but not energy expenditure in lean subjects

Pavlina Chrysafi, Nikolaos Perakakis, Olivia M. Farr, Konstantinos Stefanakis, Natia Peradze, Aleix Sala-Vila and Christos S. Mantzoros ()
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Pavlina Chrysafi: Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School
Nikolaos Perakakis: Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School
Olivia M. Farr: Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School
Konstantinos Stefanakis: Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School
Natia Peradze: Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School
Aleix Sala-Vila: Barcelonaβeta Brain Research Center, Pasqual Maragall Foundation
Christos S. Mantzoros: Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School

Nature Communications, 2020, vol. 11, issue 1, 1-15

Abstract: Abstract Based on studies in mice, leptin was expected to decrease body weight in obese individuals. However, the majority of the obese are hyperleptinemic and do not respond to leptin treatment, suggesting the presence of leptin tolerance and questioning the role of leptin as regulator of energy balance in humans. We thus performed detailed novel measurements and analyses of samples and data from our clinical trials biobank to investigate leptin effects on mechanisms of weight regulation in lean normo- and mildly hypo-leptinemic individuals without genetic disorders. We demonstrate that short-term leptin administration alters food intake during refeeding after fasting, whereas long-term leptin treatment reduces fat mass and body weight, and transiently alters circulating free fatty acids in lean mildly hypoleptinemic individuals. Leptin levels before treatment initiation and leptin dose do not predict the observed weight loss in lean individuals suggesting a saturable effect of leptin. In contrast to data from animal studies, leptin treatment does not affect energy expenditure, lipid utilization, SNS activity, heart rate, blood pressure or lean body mass.

Date: 2020
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DOI: 10.1038/s41467-020-18885-9

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