Journal article
Exercise leads to unfavourable cardiac remodelling and enhanced metabolic homeostasis in obese mice with cardiac and skeletal muscle autophagy deficiency
Scientific reports, Vol.7(1), 7894
08/11/2017
DOI: 10.1038/s41598-017-08480-2
PMCID: PMC5554260
PMID: 28801668
Abstract
Autophagy is stimulated by exercise in several tissues; yet the role of skeletal and cardiac muscle-specific autophagy on the benefits of exercise training remains incompletely understood. Here, we determined the metabolic impact of exercise training in obese mice with cardiac and skeletal muscle disruption of the Autophagy related 7 gene (Atg7(h&mKO)). Muscle autophagy deficiency did not affect glucose clearance and exercise capacity in lean adult mice. High-fat diet in sedentary mice led to endoplasmic reticulum stress and aberrant mitochondrial protein expression in autophagy-deficient skeletal and cardiac muscles. Endurance exercise training partially reversed these abnormalities in skeletal muscle, but aggravated those in the heart also causing cardiac fibrosis, foetal gene reprogramming, and impaired mitochondrial biogenesis. Interestingly, exercise-trained Atg7(h&mKO) mice were better protected against obesity and insulin resistance with increased circulating fibroblast growth factor 21 (FGF21), elevated Fgf21 mRNA and protein solely in the heart, and upregulation of FGF21-target genes involved in thermogenesis and fatty acid oxidation in brown fat. These results indicate that autophagy is essential for the protective effects of exercise in the heart. However, the atypical remodelling elicited by exercise in the autophagy deficient cardiac muscle enhances whole-body metabolism, at least partially, via a heart-brown fat cross-talk involving FGF21.
Details
- Title: Subtitle
- Exercise leads to unfavourable cardiac remodelling and enhanced metabolic homeostasis in obese mice with cardiac and skeletal muscle autophagy deficiency
- Creators
- Zhen Yan - University of VirginiaAna Kronemberger - University of IowaJay Blomme - University of IowaJarrod A. Call - University of VirginiaHannah M. Caster - University of IowaRenata O. Pereira - Roy J. and Lucille A. Carver College of MedicineHenan Zhao - University of VirginiaVitor U. de Melo - University of IowaRhianna C. Laker - University of VirginiaMei Zhang - University of VirginiaVitor A. Lira - University of Iowa
- Resource Type
- Journal article
- Publication Details
- Scientific reports, Vol.7(1), 7894
- DOI
- 10.1038/s41598-017-08480-2
- PMID
- 28801668
- PMCID
- PMC5554260
- NLM abbreviation
- Sci Rep
- ISSN
- 2045-2322
- eISSN
- 2045-2322
- Publisher
- NATURE PORTFOLIO
- Number of pages
- 15
- Grant note
- 16SDG30360001 / American Heart Association Grant; American Heart Association AR050429 / NIH; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA R01AR050429 / NATIONAL INSTITUTE OF ARTHRITIS AND MUSCULOSKELETAL AND SKIN DISEASES; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Institute of Arthritis & Musculoskeletal & Skin Diseases (NIAMS) BEX 6292/15-1 / Coordenacao de Aperfeicoamento de Pessoal de Nivel Superior CAPES/Proc
- Language
- English
- Date published
- 08/11/2017
- Academic Unit
- Family and Community Medicine; Fraternal Order of Eagles Diabetes Research Center; Endocrinology and Metabolism; Health, Sport, and Human Physiology ; Internal Medicine
- Record Identifier
- 9984259399302771
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