title: mTOR regulates fatty infiltration through SREBP-1 and PPARγ after a combined massive rotator cuff tear and suprascapular nerve injury in rats.
abstract: Rotator cuff tears (RCTs) are among the most common injuries seen in orthopedic patients. Chronic tears can result in the development of muscular atrophy and fatty infiltration. Despite the prevalence of RCTs, little is known about the underlying molecular pathways that produce these changes. Recently, we have shown that mammalian target of rapamycin (mTOR) signaling plays an important role in muscle atrophy that results from massive RCTs in a rat model. The purpose of this study was therefore to extend our understanding of mTOR signaling and evaluate its role in fatty infiltration after a combined tendon transection and suprascapular nerve denervation surgery. Akt/mTOR signaling was significantly increased and resulted in the up-regulation of two transcription factors: SREBP-1 and PPARγ. We also saw an increase in expression of adipogenic markers: C/EBP-α and FASN. Upon treatment with rapamycin, an inhibitor of mTOR, we observed a decrease in mTOR signaling, activity of transcription factors, and reduction in fatty infiltration. Therefore, our study suggests that mTOR signaling mediates rotator cuff fatty infiltration via SREBP-1 and PPARγ. Clinically, our finding may alter current treatment methods to address rotator cuff fatty infiltration.
authors.affiliation: San Francisco Veterans Affairs Medical Center, Department of Veterans Affairs, University of California, 1500 Owens Avenue, San Francisco, CA 94153, USA.
authors.forename: Sunil K
authors.initials: SK
authors.lastname: Joshi
authors.forename: Xuhui
authors.initials: X
authors.lastname: Liu
authors.forename: Sanjum P
authors.initials: SP
authors.lastname: Samagh
authors.forename: David H
authors.initials: DH
authors.lastname: Lovett
authors.forename: Sue C
authors.initials: SC
authors.lastname: Bodine
authors.forename: Hubert T
authors.initials: HT
authors.lastname: Kim
authors.forename: Brian T
authors.initials: BT
authors.lastname: Feeley
mesh_terms: D050156:Adipogenesis / Q000502:physiology; D000273:Adipose Tissue / Q000378:metabolism / Q000503:physiopathology; D000818:Animals; D005260:Female; D009121:Muscle Denervation; D018482:Muscle, Skeletal / Q000294:innervation / Q000378:metabolism / Q000503:physiopathology; D009133:Muscular Atrophy / Q000503:physiopathology; D047495:PPAR gamma / Q000378:metabolism / Q000502:physiology*; D059348:Peripheral Nerve Injuries / Q000503:physiopathology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D017006:Rotator Cuff / Q000294:innervation / Q000503:physiopathology; D000070636:Rotator Cuff Injuries; D015398:Signal Transduction / Q000502:physiology; D051780:Sterol Regulatory Element Binding Protein 1 / Q000378:metabolism / Q000502:physiology*; D058570:TOR Serine-Threonine Kinases / Q000378:metabolism / Q000502:physiology*; D013708:Tendon Injuries / Q000503:physiopathology*; D015854:Up-Regulation / Q000502:physiology
chemical_list: D047495:PPAR gamma; C497389:Srebf1 protein, rat; D051780:Sterol Regulatory Element Binding Protein 1; C546845:mTOR protein, rat; D058570:TOR Serine-Threonine Kinases