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Myostatin Inhibition Prevents Diabetes and Hyperphagia in a Mouse Model of Lipodystrophy
Lipodystrophies are characterized by a loss of white adipose tissue, which causes ectopic lipid deposition, peripheral insulin resistance, reduced adipokine levels, and increased food intake (hyperphagia). The growth factor myostatin (MSTN) negatively regulates skeletal muscle growth, and mice with...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
American Diabetes Association
2012
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3447905/ https://www.ncbi.nlm.nih.gov/pubmed/22596054 http://dx.doi.org/10.2337/db11-0915 |
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author | Guo, Tingqing Bond, Nichole D. Jou, William Gavrilova, Oksana Portas, Jennifer McPherron, Alexandra C. |
author_facet | Guo, Tingqing Bond, Nichole D. Jou, William Gavrilova, Oksana Portas, Jennifer McPherron, Alexandra C. |
author_sort | Guo, Tingqing |
collection | PubMed |
description | Lipodystrophies are characterized by a loss of white adipose tissue, which causes ectopic lipid deposition, peripheral insulin resistance, reduced adipokine levels, and increased food intake (hyperphagia). The growth factor myostatin (MSTN) negatively regulates skeletal muscle growth, and mice with MSTN inhibition have reduced adiposity and improved insulin sensitivity. MSTN inhibition may therefore be efficacious in ameliorating diabetes. To test this hypothesis, we inhibited MSTN signaling in a diabetic model of generalized lipodystrophy to analyze its effects on glucose metabolism separate from effects on adipose mass. A-ZIP/F1 lipodystrophic mice were crossed to mice expressing a dominant-negative MSTN receptor (activin receptor type IIB) in muscle. MSTN inhibition in A-ZIP/F1 mice reduced blood glucose, serum insulin, triglyceride levels, and the rate of triglyceride synthesis, and improved insulin sensitivity. Unexpectedly, hyperphagia was normalized by MSTN inhibition in muscle. Blood glucose and hyperphagia were reduced in double mutants independent of the adipokine leptin. These results show that the effect of MSTN inhibition on insulin sensitivity is not secondary to an effect on adipose mass and that MSTN inhibition may be an effective treatment for diabetes. These results further suggest that muscle may play a heretofore unappreciated role in regulating food intake. |
format | Online Article Text |
id | pubmed-3447905 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2012 |
publisher | American Diabetes Association |
record_format | MEDLINE/PubMed |
spelling | pubmed-34479052013-10-01 Myostatin Inhibition Prevents Diabetes and Hyperphagia in a Mouse Model of Lipodystrophy Guo, Tingqing Bond, Nichole D. Jou, William Gavrilova, Oksana Portas, Jennifer McPherron, Alexandra C. Diabetes Metabolism Lipodystrophies are characterized by a loss of white adipose tissue, which causes ectopic lipid deposition, peripheral insulin resistance, reduced adipokine levels, and increased food intake (hyperphagia). The growth factor myostatin (MSTN) negatively regulates skeletal muscle growth, and mice with MSTN inhibition have reduced adiposity and improved insulin sensitivity. MSTN inhibition may therefore be efficacious in ameliorating diabetes. To test this hypothesis, we inhibited MSTN signaling in a diabetic model of generalized lipodystrophy to analyze its effects on glucose metabolism separate from effects on adipose mass. A-ZIP/F1 lipodystrophic mice were crossed to mice expressing a dominant-negative MSTN receptor (activin receptor type IIB) in muscle. MSTN inhibition in A-ZIP/F1 mice reduced blood glucose, serum insulin, triglyceride levels, and the rate of triglyceride synthesis, and improved insulin sensitivity. Unexpectedly, hyperphagia was normalized by MSTN inhibition in muscle. Blood glucose and hyperphagia were reduced in double mutants independent of the adipokine leptin. These results show that the effect of MSTN inhibition on insulin sensitivity is not secondary to an effect on adipose mass and that MSTN inhibition may be an effective treatment for diabetes. These results further suggest that muscle may play a heretofore unappreciated role in regulating food intake. American Diabetes Association 2012-10 2012-09-13 /pmc/articles/PMC3447905/ /pubmed/22596054 http://dx.doi.org/10.2337/db11-0915 Text en © 2012 by the American Diabetes Association. Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered. See http://creativecommons.org/licenses/by-nc-nd/3.0/ for details. |
spellingShingle | Metabolism Guo, Tingqing Bond, Nichole D. Jou, William Gavrilova, Oksana Portas, Jennifer McPherron, Alexandra C. Myostatin Inhibition Prevents Diabetes and Hyperphagia in a Mouse Model of Lipodystrophy |
title | Myostatin Inhibition Prevents Diabetes and Hyperphagia in a Mouse Model of Lipodystrophy |
title_full | Myostatin Inhibition Prevents Diabetes and Hyperphagia in a Mouse Model of Lipodystrophy |
title_fullStr | Myostatin Inhibition Prevents Diabetes and Hyperphagia in a Mouse Model of Lipodystrophy |
title_full_unstemmed | Myostatin Inhibition Prevents Diabetes and Hyperphagia in a Mouse Model of Lipodystrophy |
title_short | Myostatin Inhibition Prevents Diabetes and Hyperphagia in a Mouse Model of Lipodystrophy |
title_sort | myostatin inhibition prevents diabetes and hyperphagia in a mouse model of lipodystrophy |
topic | Metabolism |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3447905/ https://www.ncbi.nlm.nih.gov/pubmed/22596054 http://dx.doi.org/10.2337/db11-0915 |
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