Adipose Triglyceride Lipase Activity in Adipocytes, but Not Skeletal Myocytes, Is Essential for Maintaining Normal Contractile Function in Both Young and Old Mice

The production of contractile force is a key physiological function of skeletal muscle which relies on many factors in order to reach maximal force output. While the working muscle requires sufficient energy substrates to maintain work, for maximal contractile force development to occur, skeletal muscle requires multiple motor units to be recruited thereby allowing fibers to unite their contractions. This recruitment process depends on multiple factors such as muscle fiber size, lack of injury and, neuromuscular signaling. As such, maximal force output is often an indicator of overall skeletal muscle quality, with lower quality (e.g. no infiltration of fat or fibrotic tissue) or injured muscle having impaired maximal force production. Adipose Triglyceride Lipase (ATGL) is the rate‐limiting enzyme mediating intracellular triacylglycerol hydrolysis and plays a key role in the mobilization of fatty acids during exercise. However, it likely also plays a role in skeletal muscle physiology as a total loss of ATGL leads to a dystrophic phenotype with progressive myopathies, weakness and impaired exercise performance. In order to determine the role between ATGL mediated lipolysis and skeletal muscle functional performance, we generated adipocyte or skeletal myocyte‐specific ATGL knockout mice and assessed their capacity for force production in both young and older animals. We found that the loss of ATGL‐mediated lipolysis in either muscle or adipose had no effect on twitch force or fatigue resistance compared to wild‐type controls. However, the loss of ATGL activity in adipose tissue resulted in severe impairments in their force frequency profile, particularly at frequencies that elicit a summation of contractions. Together this suggests that adipocyte ATGL‐mediated lipolysis could play a significant role in skeletal muscle function and overall muscle quality. For further analysis, we are planning to investigate changes in gene and protein expression alongside histochemical assessment of muscle architecture and injury to derive a possible mechanism for our observed phenotype phenotype. Support or Funding Information This work was supported by NIH R01DK090166, HHMI Physician‐Scientist Early Career Award, and U. of Pittsburgh Dept of Medicine Junior Scholar Award; NIH T32 DK007052; Erwin Schrödinger Fellowship‐J3221‐B19, the Claude D. Pepper Center for Aging Pilot award, and the MSU Science, Honors, and Innovation Program This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal .