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In this study we compared the function of skinned fiber bundles from transgenic (Tg) mice that overexpress a relatively low level of the peroxisome proliferator-activated receptor \u03b1 (PPAR\u03b1), and nontransgenic (NTg) littermates. The mice (NTg-T and Tg-T) were stressed by transverse aortic constriction (TAC) and compared with shams (NTg-S and Tg-S). There was an approximate 4-fold increase in PPAR\u03b1 expression in Tg-S compared with NTg-S, but Tg-T hearts showed the same PPAR\u03b1 expression as NTg-T. Expression of PPAR\u03b1 did not alter the hypertrophic response to TAC but did reduce ejection fraction (EF) in Tg-T hearts compared with other groups. The rate of actomyosin ATP hydrolysis was significantly higher in Tg-S skinned fiber bundles compared with all other groups. Tg-T hearts showed an increase in phosphorylation of specific sites on cardiac myosin binding protein-C (cMyBP-C) and \u03b2-myosin heavy chain isoform. These results advance our understanding of potential signaling to the myofilaments induced by altered FA metabolism under normal and pathological states. We demonstrate that chronic and transient PPAR\u03b1 activation during pathological stress alters myofilament response to Ca<jats:sup>2+<\/jats:sup>through a mechanism that is possibly mediated by MyBP-C phosphorylation and myosin heavy chain isoforms.<\/jats:p><jats:p>NEW &amp; NOTEWORTHY Data presented here demonstrate novel signaling to sarcomeric proteins by chronic alterations in fatty acid metabolism induced by PPAR\u03b1. The mechanism involves modifications of key myofilament regulatory proteins modifying cross-bridge dynamics with differential effects in controls and hearts stressed by pressure overload.<\/jats:p>","DOI":"10.1152\/ajpheart.00469.2016","type":"journal-article","created":{"date-parts":[[2017,1,28]],"date-time":"2017-01-28T03:10:19Z","timestamp":1485573019000},"page":"H681-H690","source":"Crossref","is-referenced-by-count":11,"title":["Peroxisome proliferator-activated receptor-\u03b1 expression induces alterations in cardiac myofilaments in a pressure-overload model of hypertrophy"],"prefix":"10.1152","volume":"312","author":[{"given":"Chehade N.","family":"Karam","sequence":"first","affiliation":[{"name":"Department of Physiology &amp; Biophysics, Center for Cardiovascular Research, University of Illinois at Chicago, Chicago, Illinois; and"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chad M.","family":"Warren","sequence":"additional","affiliation":[{"name":"Department of Physiology &amp; Biophysics, Center for Cardiovascular Research, University of Illinois at Chicago, Chicago, Illinois; and"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marcus","family":"Henze","sequence":"additional","affiliation":[{"name":"Department of Physiology &amp; Biophysics, Center for Cardiovascular Research, University of Illinois at Chicago, Chicago, Illinois; and"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Natasha H.","family":"Banke","sequence":"additional","affiliation":[{"name":"Department of Physiology &amp; Biophysics, Center for Cardiovascular Research, University of Illinois at Chicago, Chicago, Illinois; and"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"E. 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