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Withaferin A is a Leptin Sensitizer with Strong Anti-Diabetic Properties in Mice

The increasing global prevalence of obesity and its associated disorders point to an urgent need for the development of novel and effective therapeutic strategies that induce healthy weight loss. Obesity is characterized by hyperleptinemia and central leptin resistance. In an attempt to identify com...

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Autores principales: Lee, Jaemin, Liu, Junli, Feng, Xudong, Salazar Hernández, Mario Andrés, Mucka, Patrick, Ibi, Dorina, Choi, Jae Won, Ozcan, Umut
Formato: Online Artículo Texto
Lenguaje:English
Publicado: 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5892415/
https://www.ncbi.nlm.nih.gov/pubmed/27479085
http://dx.doi.org/10.1038/nm.4145
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author Lee, Jaemin
Liu, Junli
Feng, Xudong
Salazar Hernández, Mario Andrés
Mucka, Patrick
Ibi, Dorina
Choi, Jae Won
Ozcan, Umut
author_facet Lee, Jaemin
Liu, Junli
Feng, Xudong
Salazar Hernández, Mario Andrés
Mucka, Patrick
Ibi, Dorina
Choi, Jae Won
Ozcan, Umut
author_sort Lee, Jaemin
collection PubMed
description The increasing global prevalence of obesity and its associated disorders point to an urgent need for the development of novel and effective therapeutic strategies that induce healthy weight loss. Obesity is characterized by hyperleptinemia and central leptin resistance. In an attempt to identify compounds that could reverse leptin resistance and thus promote weight loss, we analyzed a library of small molecules with mRNA expression profiles similar to that of celastrol, a naturally-occurring compound we previously identified as a leptin sensitizer. By this process we identified another natural compound, withaferin A, that also acts as a leptin sensitizer. We found that withaferin A treatment of diet-induced obese mice resulted in a 20-25% reduction of body weight, while also decreasing obesity-associated abnormalities including hepatic steatosis. Withaferin A marginally affects the body weight of ob/ob and db/db mice, which are both deficient in leptin signaling. In addition, withaferin A, unlike celastrol, has beneficial effects on glucose metabolism independently from its leptin-sensitizing effect. Our results show that the metabolic abnormalities of diet-induced obesity can be mitigated by sensitizing animals to endogenous leptin, and indicate that withaferin A is a potential leptin sensitizer with additional anti-diabetic actions.
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spelling pubmed-58924152018-04-10 Withaferin A is a Leptin Sensitizer with Strong Anti-Diabetic Properties in Mice Lee, Jaemin Liu, Junli Feng, Xudong Salazar Hernández, Mario Andrés Mucka, Patrick Ibi, Dorina Choi, Jae Won Ozcan, Umut Nat Med Article The increasing global prevalence of obesity and its associated disorders point to an urgent need for the development of novel and effective therapeutic strategies that induce healthy weight loss. Obesity is characterized by hyperleptinemia and central leptin resistance. In an attempt to identify compounds that could reverse leptin resistance and thus promote weight loss, we analyzed a library of small molecules with mRNA expression profiles similar to that of celastrol, a naturally-occurring compound we previously identified as a leptin sensitizer. By this process we identified another natural compound, withaferin A, that also acts as a leptin sensitizer. We found that withaferin A treatment of diet-induced obese mice resulted in a 20-25% reduction of body weight, while also decreasing obesity-associated abnormalities including hepatic steatosis. Withaferin A marginally affects the body weight of ob/ob and db/db mice, which are both deficient in leptin signaling. In addition, withaferin A, unlike celastrol, has beneficial effects on glucose metabolism independently from its leptin-sensitizing effect. Our results show that the metabolic abnormalities of diet-induced obesity can be mitigated by sensitizing animals to endogenous leptin, and indicate that withaferin A is a potential leptin sensitizer with additional anti-diabetic actions. 2016-08-01 2016-09 /pmc/articles/PMC5892415/ /pubmed/27479085 http://dx.doi.org/10.1038/nm.4145 Text en http://www.nature.com/authors/editorial_policies/license.html#terms Users may view, print, copy, and download text and data-mine the content in such documents, for the purposes of academic research, subject always to the full Conditions of use:http://www.nature.com/authors/editorial_policies/license.html#terms
spellingShingle Article
Lee, Jaemin
Liu, Junli
Feng, Xudong
Salazar Hernández, Mario Andrés
Mucka, Patrick
Ibi, Dorina
Choi, Jae Won
Ozcan, Umut
Withaferin A is a Leptin Sensitizer with Strong Anti-Diabetic Properties in Mice
title Withaferin A is a Leptin Sensitizer with Strong Anti-Diabetic Properties in Mice
title_full Withaferin A is a Leptin Sensitizer with Strong Anti-Diabetic Properties in Mice
title_fullStr Withaferin A is a Leptin Sensitizer with Strong Anti-Diabetic Properties in Mice
title_full_unstemmed Withaferin A is a Leptin Sensitizer with Strong Anti-Diabetic Properties in Mice
title_short Withaferin A is a Leptin Sensitizer with Strong Anti-Diabetic Properties in Mice
title_sort withaferin a is a leptin sensitizer with strong anti-diabetic properties in mice
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5892415/
https://www.ncbi.nlm.nih.gov/pubmed/27479085
http://dx.doi.org/10.1038/nm.4145
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