1189-P: Ankyrin-B Modulates the Integrity and Bioenergetic Capacity of Skeletal Muscle Fibers
| Autor: | Joyce Tzeng, Kayleigh M Voos, Damaris N Lorenzo |
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| Rok vydání: | 2021 |
| Předmět: | |
| Zdroj: | Diabetes. 70 |
| ISSN: | 1939-327X 0012-1797 |
| Popis: | Ankyrin-B (AnkB) is a cytoskeletal protein that positions and stabilizes specialized membrane-associated protein complexes. AnkB also associates with organelles and facilitates their dynamics across cell types. AnkB variants have been linked to higher risk for obesity and type 2 diabetes (T2D) in humans and mice. In skeletal muscle (SKM), AnkB localizes to costameres and acts as a scaffold to β-dystroglycan/dystrophin complexes. This protein complex has been demonstrated to be essential for SKM integrity and exercise injury protection. However, besides this structural role, our findings suggest that AnkB associates with mitochondria in SKM and likely plays important roles in SKM bioenergetics. We found that non-obese young mice lacking AnkB solely in SKM (SKM-AnkB KO) develop early signs of myofibrillar disorganization and fibrosis and display reduced physical activity without changes in body weight, fasting glucose levels, or peripheral insulin response. In contrast, SKM-AnkB KO mice are more susceptible to the metabolic effects of a HFD, manifested as lower insulin sensitivity and further reductions in physical activity. Our findings suggest that loss of myofibril organization synergizes with changes in mitochondrial function to worsen SKM bioenergetics and insulin action. These physiological alterations are in agreement with our RNA-seq and proteomics studies, which implicate AnkB in the regulation of SKM oxidative capacity, protein translation, and cellular responses to stress and nutrient availability. We will discuss our ongoing efforts to uncover the mechanistic basis of these metabolic impairments cause by AnkB deficits. Disclosure K. Voos: None. J. Tzeng: None. D. Lorenzo: None. Funding American Diabetes Association (1-19-JDF-081 to D.L.) |
| Databáze: | OpenAIRE |
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