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

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...

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Published inNature communications Vol. 11; no. 1; pp. 5145 - 15
Main Authors Chrysafi, Pavlina, Perakakis, Nikolaos, Farr, Olivia M., Stefanakis, Konstantinos, Peradze, Natia, Sala-Vila, Aleix, Mantzoros, Christos S.
Format Journal Article
LanguageEnglish
Published London Nature Publishing Group UK 13.10.2020
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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. Leptin treatment is effective to reduce body weight in animal models, but patients with obesity and associated hyperleptinemia do not respond well to leptin therapy. Here the authors report a retrospective analysis of four clinical trials in normo- and mildly hypoleptinemic individuals and show that leptin therapy alters food intake in the short term and reduces weight and fat mass in the long term without effects on energy expenditure.
AbstractList 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. Leptin treatment is effective to reduce body weight in animal models, but patients with obesity and associated hyperleptinemia do not respond well to leptin therapy. Here the authors report a retrospective analysis of four clinical trials in normo- and mildly hypoleptinemic individuals and show that leptin therapy alters food intake in the short term and reduces weight and fat mass in the long term without effects on energy expenditure.
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.
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.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.
Leptin treatment is effective to reduce body weight in animal models, but patients with obesity and associated hyperleptinemia do not respond well to leptin therapy. Here the authors report a retrospective analysis of four clinical trials in normo- and mildly hypoleptinemic individuals and show that leptin therapy alters food intake in the short term and reduces weight and fat mass in the long term without effects on energy expenditure.
ArticleNumber 5145
Author Peradze, Natia
Farr, Olivia M.
Sala-Vila, Aleix
Chrysafi, Pavlina
Perakakis, Nikolaos
Stefanakis, Konstantinos
Mantzoros, Christos S.
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  surname: Perakakis
  fullname: Perakakis, Nikolaos
  organization: Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School
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  givenname: Olivia M.
  surname: Farr
  fullname: Farr, Olivia M.
  organization: Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School
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  givenname: Konstantinos
  surname: Stefanakis
  fullname: Stefanakis, Konstantinos
  organization: Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School
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  givenname: Natia
  surname: Peradze
  fullname: Peradze, Natia
  organization: Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School
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  givenname: Aleix
  surname: Sala-Vila
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  organization: Barcelonaβeta Brain Research Center, Pasqual Maragall Foundation, Institut Hospital del Mar d’Investigacions Mèdiques (IMIM)
– sequence: 7
  givenname: Christos S.
  orcidid: 0000-0003-3755-8158
  surname: Mantzoros
  fullname: Mantzoros, Christos S.
  email: cmantzor@bidmc.harvard.edu
  organization: Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School
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Snippet 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...
Leptin treatment is effective to reduce body weight in animal models, but patients with obesity and associated hyperleptinemia do not respond well to leptin...
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Title Leptin alters energy intake and fat mass but not energy expenditure in lean subjects
URI https://link.springer.com/article/10.1038/s41467-020-18885-9
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Volume 11
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