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Leptin Improves Parameters of Brown Adipose Tissue Thermogenesis in Lipodystrophic Mice

Lipodystrophy syndromes (LD) are a heterogeneous group of very rare congenital or acquired disorders characterized by a generalized or partial lack of adipose tissue. They are strongly associated with severe metabolic dysfunction due to ectopic fat accumulation in the liver and other organs and the...

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Autores principales: Hoffmann, Annett, Ebert, Thomas, Hankir, Mohammed K., Flehmig, Gesine, Klöting, Nora, Jessnitzer, Beate, Lössner, Ulrike, Stumvoll, Michael, Blüher, Matthias, Fasshauer, Mathias, Tönjes, Anke, Miehle, Konstanze, Kralisch, Susan
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8399124/
https://www.ncbi.nlm.nih.gov/pubmed/34444659
http://dx.doi.org/10.3390/nu13082499
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author Hoffmann, Annett
Ebert, Thomas
Hankir, Mohammed K.
Flehmig, Gesine
Klöting, Nora
Jessnitzer, Beate
Lössner, Ulrike
Stumvoll, Michael
Blüher, Matthias
Fasshauer, Mathias
Tönjes, Anke
Miehle, Konstanze
Kralisch, Susan
author_facet Hoffmann, Annett
Ebert, Thomas
Hankir, Mohammed K.
Flehmig, Gesine
Klöting, Nora
Jessnitzer, Beate
Lössner, Ulrike
Stumvoll, Michael
Blüher, Matthias
Fasshauer, Mathias
Tönjes, Anke
Miehle, Konstanze
Kralisch, Susan
author_sort Hoffmann, Annett
collection PubMed
description Lipodystrophy syndromes (LD) are a heterogeneous group of very rare congenital or acquired disorders characterized by a generalized or partial lack of adipose tissue. They are strongly associated with severe metabolic dysfunction due to ectopic fat accumulation in the liver and other organs and the dysregulation of several key adipokines, including leptin. Treatment with leptin or its analogues is therefore sufficient to reverse some of the metabolic symptoms of LD in patients and in mouse models through distinct mechanisms. Brown adipose tissue (BAT) thermogenesis has emerged as an important regulator of systemic metabolism in rodents and in humans, but it is poorly understood how leptin impacts BAT in LD. Here, we show in transgenic C57Bl/6 mice overexpressing sterol regulatory element-binding protein 1c in adipose tissue (Tg (aP2-nSREBP1c)), an established model of congenital LD, that daily subcutaneous administration of 3 mg/kg leptin for 6 to 8 weeks increases body temperature without affecting food intake or body weight. This is associated with increased protein expression of the thermogenic molecule uncoupling protein 1 (UCP1) and the sympathetic nerve marker tyrosine hydroxylase (TH) in BAT. These findings suggest that leptin treatment in LD stimulates BAT thermogenesis through sympathetic nerves, which might contribute to some of its metabolic benefits by providing a healthy reservoir for excess circulating nutrients.
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spelling pubmed-83991242021-08-29 Leptin Improves Parameters of Brown Adipose Tissue Thermogenesis in Lipodystrophic Mice Hoffmann, Annett Ebert, Thomas Hankir, Mohammed K. Flehmig, Gesine Klöting, Nora Jessnitzer, Beate Lössner, Ulrike Stumvoll, Michael Blüher, Matthias Fasshauer, Mathias Tönjes, Anke Miehle, Konstanze Kralisch, Susan Nutrients Article Lipodystrophy syndromes (LD) are a heterogeneous group of very rare congenital or acquired disorders characterized by a generalized or partial lack of adipose tissue. They are strongly associated with severe metabolic dysfunction due to ectopic fat accumulation in the liver and other organs and the dysregulation of several key adipokines, including leptin. Treatment with leptin or its analogues is therefore sufficient to reverse some of the metabolic symptoms of LD in patients and in mouse models through distinct mechanisms. Brown adipose tissue (BAT) thermogenesis has emerged as an important regulator of systemic metabolism in rodents and in humans, but it is poorly understood how leptin impacts BAT in LD. Here, we show in transgenic C57Bl/6 mice overexpressing sterol regulatory element-binding protein 1c in adipose tissue (Tg (aP2-nSREBP1c)), an established model of congenital LD, that daily subcutaneous administration of 3 mg/kg leptin for 6 to 8 weeks increases body temperature without affecting food intake or body weight. This is associated with increased protein expression of the thermogenic molecule uncoupling protein 1 (UCP1) and the sympathetic nerve marker tyrosine hydroxylase (TH) in BAT. These findings suggest that leptin treatment in LD stimulates BAT thermogenesis through sympathetic nerves, which might contribute to some of its metabolic benefits by providing a healthy reservoir for excess circulating nutrients. MDPI 2021-07-22 /pmc/articles/PMC8399124/ /pubmed/34444659 http://dx.doi.org/10.3390/nu13082499 Text en © 2021 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Hoffmann, Annett
Ebert, Thomas
Hankir, Mohammed K.
Flehmig, Gesine
Klöting, Nora
Jessnitzer, Beate
Lössner, Ulrike
Stumvoll, Michael
Blüher, Matthias
Fasshauer, Mathias
Tönjes, Anke
Miehle, Konstanze
Kralisch, Susan
Leptin Improves Parameters of Brown Adipose Tissue Thermogenesis in Lipodystrophic Mice
title Leptin Improves Parameters of Brown Adipose Tissue Thermogenesis in Lipodystrophic Mice
title_full Leptin Improves Parameters of Brown Adipose Tissue Thermogenesis in Lipodystrophic Mice
title_fullStr Leptin Improves Parameters of Brown Adipose Tissue Thermogenesis in Lipodystrophic Mice
title_full_unstemmed Leptin Improves Parameters of Brown Adipose Tissue Thermogenesis in Lipodystrophic Mice
title_short Leptin Improves Parameters of Brown Adipose Tissue Thermogenesis in Lipodystrophic Mice
title_sort leptin improves parameters of brown adipose tissue thermogenesis in lipodystrophic mice
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8399124/
https://www.ncbi.nlm.nih.gov/pubmed/34444659
http://dx.doi.org/10.3390/nu13082499
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