PMID- 17980390 OWN - NLM STAT- MEDLINE DCOM- 20080319 LR - 20131121 IS - 0022-5193 (Print) IS - 0022-5193 (Linking) VI - 250 IP - 1 DP - 2008 Jan 7 TI - Increased entropy production in diaphragm muscle of PPAR alpha knockout mice. PG - 92-102 AB - Peroxisome proliferator activated receptor alpha (PPAR alpha) regulates fatty acid beta-oxidation (FAO) and plays a central role in the metabolic and energetic homeostasis of striated muscles. The thermodynamic consequences of the absence of PPAR alpha were investigated in diaphragm muscle of PPAR alpha knockout mice (KO). Statistical mechanics provides a powerful tool for determining entropy production, which quantifies irreversible chemical processes generated by myosin molecular motors and which is the product of thermodynamic force A/T (chemical affinity A and temperature T) and thermodynamic flow (myosin crossbridge (CB) cycle velocity upsilon). The behavior of both wild type (WT) and KO diaphragm was shown to be near-equilibrium and in a stationary state, but KO was farther from equilibrium than WT. In KO diaphragm, a substantial decrease in contractile function was associated with an increase in both A/T and upsilon and with profound histological injuries such as contraction band necrosis. There were no changes in PPAR delta and gamma expression levels or myosin heavy chain (MHC) patterns. In KO diaphragm, a marked increase in entropy production (A/T x upsilon) accounted for major thermodynamic dysfunction and a dramatic increase in irreversible chemical processes during the myosin CB cycle. FAU - Lecarpentier, Y AU - Lecarpentier Y AD - Service de Physiologie, Hopital de Bicetre, Assistance Publique-Hopitaux de Paris, Universite Paris 11, Le Kremlin-Bicetre, France. yves.lecarpentier@bct.ap-hp-paris.fr FAU - Krokidis, X AU - Krokidis X FAU - Martin, P AU - Martin P FAU - Pineau, T AU - Pineau T FAU - Hebert, J-L AU - Hebert JL FAU - Quillard, J AU - Quillard J FAU - Cortes-Morichetti, M AU - Cortes-Morichetti M FAU - Coirault, C AU - Coirault C LA - eng PT - Journal Article DEP - 20070921 PL - England TA - J Theor Biol JT - Journal of theoretical biology JID - 0376342 RN - 0 (PPAR alpha) RN - 0 (PPAR delta) RN - 0 (PPAR gamma) RN - 0 (Protein Isoforms) RN - 0 (RNA, Messenger) RN - EC 3.6.4.1 (Myosin Heavy Chains) RN - EC 3.6.4.1 (Myosins) SB - IM MH - Animals MH - Body Weight MH - Diaphragm/metabolism/pathology/*physiopathology MH - Entropy MH - Gene Expression Regulation MH - Male MH - Mice MH - Mice, Inbred C57BL MH - Mice, Knockout MH - Myosin Heavy Chains/analysis MH - Myosins/metabolism MH - PPAR alpha/biosynthesis/*deficiency/genetics MH - PPAR delta/biosynthesis/genetics MH - PPAR gamma/biosynthesis/genetics MH - Protein Isoforms/analysis MH - RNA, Messenger/genetics MH - Reverse Transcriptase Polymerase Chain Reaction/methods MH - Thermodynamics EDAT- 2007/11/06 09:00 MHDA- 2008/03/20 09:00 CRDT- 2007/11/06 09:00 PHST- 2007/04/11 00:00 [received] PHST- 2007/07/13 00:00 [revised] PHST- 2007/09/01 00:00 [accepted] PHST- 2007/11/06 09:00 [pubmed] PHST- 2008/03/20 09:00 [medline] PHST- 2007/11/06 09:00 [entrez] AID - S0022-5193(07)00426-2 [pii] AID - 10.1016/j.jtbi.2007.09.022 [doi] PST - ppublish SO - J Theor Biol. 2008 Jan 7;250(1):92-102. doi: 10.1016/j.jtbi.2007.09.022. Epub 2007 Sep 21.