Exercise leads to unfavourable cardiac remodelling and enhanced metabolic homeostasis in obese mice with cardiac and skeletal muscle autophagy deficiency.

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 (Atg7h&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 Atg7h&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.

• Authors: Zhen Yan, Ana Kronemberger, Jay Blomme, Jarrod A Call, Hannah M Caster, Renata O Pereira, Henan Zhao, Vitor U de Melo, Rhianna C Laker, Mei Zhang, Vitor A Lira
• Journal: Scientific reports (Sci Rep) Vol. 7 Issue 1 Pg. 7894 (08 11 2017) ISSN: 2045-2322 [Electronic] England
• PMID: 28801668 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

• Atg7 protein, mouse
• Autophagy-Related Protein 7
• Glucose

Topics

• Animals
• Autophagy
• Autophagy-Related Protein 7 (deficiency)
• Diet, High-Fat
• Endoplasmic Reticulum Stress
• Energy Metabolism
• Glucose (metabolism)
• Insulin Resistance
• Mice, Inbred C57BL
• Mice, Knockout
• Mice, Obese
• Muscle, Skeletal (pathology)
• Myocardium (pathology)
• Obesity
• Organelle Biogenesis
• Physical Conditioning, Animal
• Ventricular Remodeling