Chrysafi, PavlinaPerakakis,NikolaosFarr, Olivia M.Stefanakis, KonstantinosPeradze, NatiaSala Vila, AleixMantzoros, Christos S.2021-12-102021-12-102020Chrysafi P, Perakakis N, Farr OM, Stefanakis K, Peradze N, Sala-Vila A, et al. Leptin alters energy intake and fat mass but not energy expenditure in lean subjects. Nat Commun. 2020 Oct 13; 11(1): 5145. DOI: 10.1038/s41467-020-18885-92041-1723http://hdl.handle.net/10230/49167Based 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.application/pdfengCopyright © This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply 2020. Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.Teixit adipósLeptinaObesitatinfo:eu-repo/semantics/articlehttp://dx.doi.org/10.1038/s41467-020-18885-9info:eu-repo/semantics/openAccess