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Alterations in Adiposity and Glucose Homeostasis in Adult Gasp-1 Overexpressing Mice

Alterations in Adiposity and Glucose Homeostasis in Adult Gasp-1 Overexpressing Mice

Cellular Physiology and Biochemistry 44(5): 1896-1911

Myostatin is known as a powerful negative regulator of muscle growth playing a key role in skeletal muscle homeostasis. Recent studies revealed that myostatin-deficient mice lead to an increase of insulin sensitivity, a decrease of adiposity and a resistance to obesity, showing that myostatin can also impact on metabolism. Thus, myostatin appeared as a potential therapeutic target to treat insulin resistance. We generated transgenic mice overexpressing Gasp-1, a myostatin inhibitor. Surprisingly, we found that these mice gained weight with age due to an increase in fat mass associated with ectopic fat accumulation. In addition, these mice developed an adipocyte hypertrophy, hyperglycemia, hyperinsulinemia, muscle and hepatic insulin resistance. Understanding the molecular networks controlling this insulin resistance responsiveness in overexpressing Gasp-1 mice is essential. Molecular analyses revealed a deregulation of adipokines and muscle cytokines expression, but also an increase in plasma myostatin levels. The increase in myostatin bioactivity by a positive feedback mechanism in the Tg(Gasp-1) transgenic mice could lead to this combination of phenotypes. Altogether, these data suggested that overexpressing Gasp-1 mice develop most of the symptoms associated with metabolic syndrome and could be a relevant model for the study of obesity or type 2 diabetes.

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Accession: 045985781

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PMID: 29224025

DOI: 10.1159/000485878

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