Diet‐induced obesity alters anabolic signalling in mice at the onset of skeletal muscle regeneration

<jats:title>Abstract</jats:title><jats:sec><jats:title>Aim</jats:title><jats:p>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 (<jats:styled-content style="fixed-case">MRF</jats:styled-content>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.</jats:p></jats:sec><jats:sec><jats:title>Methods</jats:title><jats:p>Forty‐eight male C57BL/6J mice (3 weeks old) were randomly assigned to either a high‐fat diet (<jats:styled-content style="fixed-case">HFD</jats:styled-content>, 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 (<jats:italic>n</jats:italic> = 5–8/group) and <jats:styled-content style="fixed-case">PBS</jats:styled-content> was injected into the control (<jats:italic>n</jats:italic> = 5–6). The <jats:styled-content style="fixed-case">TA</jats:styled-content> was excised 3 or 28 days after injection.</jats:p></jats:sec><jats:sec><jats:title>Results</jats:title><jats:p>We demonstrated impaired muscle regeneration in obese mice. The obese mice had reduced <jats:styled-content style="fixed-case">IL</jats:styled-content>‐6, MyoD and <jats:styled-content style="fixed-case">IGF</jats:styled-content>‐1 <jats:styled-content style="fixed-case">mRNA</jats:styled-content> abundance compared to the lean mice (<jats:italic>P </jats:italic><<jats:italic> </jats:italic>0.05). Three days following muscle damage, <jats:styled-content style="fixed-case">TNF</jats:styled-content>‐<jats:italic>α </jats:italic><jats:styled-content style="fixed-case">mRNA</jats:styled-content> and protein levels of P‐<jats:styled-content style="fixed-case">STAT</jats:styled-content>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.</jats:p></jats:sec><jats:sec><jats:title>Conclusion</jats:title><jats:p>Obese mice have impaired inflammatory and protein synthetic signalling that may negatively influence muscle regeneration.</jats:p></jats:sec>