Maunder, EdRothschild, Jeffrey AFritzen, Andreas MJordy, Andreas BKiens, BenteBrick, Matthew JLeigh, Warren BChang, Wee-LeongKilding, Andrew E2023-11-272023-11-272023-07-14Pflugers Arch, ISSN: 1432-2013 (Print); 1432-2013 (Online), Springer Science and Business Media LLC, 475(9), 1061-1072. doi: 10.1007/s00424-023-02843-71432-20131432-2013http://hdl.handle.net/10292/17011Several proteins are implicated in transmembrane fatty acid transport. The purpose of this study was to quantify the variation in fatty acid oxidation rates during exercise explained by skeletal muscle proteins involved in fatty acid transport. Seventeen endurance-trained males underwent a (i) fasted, incremental cycling test to estimate peak whole-body fatty acid oxidation rate (PFO), (ii) resting vastus lateralis microbiopsy, and (iii) 2 h of fed-state, moderate-intensity cycling to estimate whole-body fatty acid oxidation during fed-state exercise (FO). Bivariate correlations and stepwise linear regression models of PFO and FO during 0-30 min (early FO) and 90-120 min (late FO) of continuous cycling were constructed using muscle data. To assess the causal role of transmembrane fatty acid transport in fatty acid oxidation rates during exercise, we measured fatty acid oxidation during in vivo exercise and ex vivo contractions in wild-type and CD36 knock-out mice. We observed a novel, positive association between vastus lateralis FATP1 and PFO and replicated work reporting a positive association between FABPpm and PFO. The stepwise linear regression model of PFO retained CD36, FATP1, FATP4, and FABPpm, explaining ~87% of the variation. Models of early and late FO explained ~61 and ~65% of the variation, respectively. FATP1 and FATP4 emerged as contributors to models of PFO and FO. Mice lacking CD36 had impaired whole-body and muscle fatty acid oxidation during exercise and muscle contractions, respectively. These data suggest that substantial variation in fatty acid oxidation rates during exercise can be explained by skeletal muscle proteins involved in fatty acid transport.Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.http://creativecommons.org/licenses/by/4.0/CyclingFat metabolismMuscleTransportersCyclingFat metabolismMuscleTransporters3101 Biochemistry and Cell Biology32 Biomedical and Clinical Sciences31 Biological Sciences3109 Zoology3208 Medical PhysiologyCardiovascularPreventionHeart DiseaseMusculoskeletal0606 Physiology1106 Human Movement and Sports Sciences1116 Medical PhysiologyPhysiology3101 Biochemistry and cell biology3109 Zoology3208 Medical physiologyMaleMiceAnimalsFatty Acid Transport ProteinsMuscle ProteinsMuscle, SkeletalCD36 AntigensFatty AcidsOxidation-ReductionMuscle, SkeletalAnimalsMiceFatty AcidsMuscle ProteinsOxidation-ReductionMaleFatty Acid Transport ProteinsCD36 AntigensMaleMiceAnimalsFatty Acid Transport ProteinsMuscle ProteinsMuscle, SkeletalCD36 AntigensFatty AcidsOxidation-ReductionJournal ArticleOpenAccess10.1007/s00424-023-02843-7