Antagonizing PPARγ improves muscle fiber force production and reduces lipid infiltration following chronic muscle injury (1163.20)

Abstract

Following chronic tears, certain muscle groups develop an accumulation of ectopic fat within muscle fibers, as well as in plaques within the extracellular matrix. Muscle atrophy, fibrosis and inflammation often accompany this fat infiltration, and these changes are commonly referred to as “fatty degeneration.” As PPARγ is a potent inducer of adipogenesis, we tested the hypothesis that antagonizing PPARγ signaling would reduce fatty degeneration and increase muscle fiber specific force production in a rat full-thickness severe rotator cuff tear model. Rats were subjected to a full thickness tenectomy of the supraspinatus and infraspinatus tendons and received either standard chow or chow infused with the PPARγ antagonist GW9662. Thirty days after tear, muscles were harvested and prepared for muscle fiber contractility, histology, and RNA isolation. Compared with control rats, torn muscles from PPARγ antagonist rats exhibited a 15% increase in specific force production. Additionally, antagonizing PPARγ reduced the amount of lipid plaques, along with a downregulation of several mRNA transcripts involved in canonical muscle lipid metabolism, macrophage accumulation, atrophy, autophagy and fibrosis. While further studies are necessary, the results from the current work support PPARγ as a potential therapeutic target for the treatment of fatty degeneration in chronic muscle tears.