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Diet‐induced obesity alters anabolic signalling in mice at the onset of skeletal muscle regeneration
Author(s) -
Brown L. A.,
Lee D. E.,
Patton J. F.,
Perry R. A.,
Brown J. L.,
Baum J. I.,
SmithBlair N.,
Greene N. P.,
Washington T. A.
Publication year - 2015
Publication title -
acta physiologica
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.591
H-Index - 116
eISSN - 1748-1716
pISSN - 1748-1708
DOI - 10.1111/apha.12537
Subject(s) - endocrinology , medicine , skeletal muscle , myod , anabolism , regeneration (biology) , inflammation , diet induced obese , myogenin , biology , tibialis anterior muscle , obesity , myogenesis , insulin resistance , microbiology and biotechnology
Aim Obesity is classified as a metabolic disorder that is associated with delayed muscle regeneration following damage. For optimal skeletal muscle regeneration, inflammation along with extracellular matrix remodelling and muscle growth must be tightly regulated. Moreover, the regenerative process is dependent on the activation of myogenic regulatory factors ( MRF s) for myoblast proliferation and differentiation. The purpose of this study was to determine how obesity alters inflammatory and protein synthetic signalling and MRF expression at the onset of muscle regeneration in mice. Methods Forty‐eight male C57BL/6J mice (3 weeks old) were randomly assigned to either a high‐fat diet ( HFD , 60% fat) or a lean diet (10% fat) for 12 weeks. At 15 weeks, bupivacaine was injected into the tibialis anterior (TA) of the injured group ( n = 5–8/group) and PBS was injected into the control ( n = 5–6). The TA was excised 3 or 28 days after injection. Results We demonstrated impaired muscle regeneration in obese mice. The obese mice had reduced IL ‐6, MyoD and IGF ‐1 mRNA abundance compared to the lean mice ( P < 0.05). Three days following muscle damage, TNF ‐ α mRNA and protein levels of P‐ STAT 3 and P‐Akt were 14‐fold, fourfold and fivefold greater in the lean mice respectively. However, there were no differences observed in the obese injured group compared to the uninjured group. Moreover, p70S6K1 was threefold greater in lean injured mice compared to uninjured but was reduced by 28% in the obese injured mice. Conclusion Obese mice have impaired inflammatory and protein synthetic signalling that may negatively influence muscle regeneration.