McFarlan 2012 J Biol Chem

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McFarlan JT, Yoshida Y, Jain SS, Han XX, Snook LA, Lally J, Smith BK, Glatz JF, Luiken JJ, Sayer RA, Tupling AR, Chabowski A, Holloway GP, Bonen A (2012) In vivo, fatty acid translocase (CD36) critically regulates skeletal muscle fuel selection, exercise performance and training-induced adaptation of fatty acid oxidation. J Biol Chem 287:23502-16.

» PMID: 22584574 Open Access

McFarlan JT, Yoshida Y, Jain SS, Han XX, Snook LA, Lally J, Smith BK, Glatz JF, Luiken JJ, Sayer RA, Tupling AR, Chabowski A, Holloway GP, Bonen A (2012) J Biol Chem

Abstract: For ~40 years it has been widely accepted that i) the exercise-induced increase in muscle fatty acid oxidation (FAO) is dependent on the increased delivery of circulating fatty acids, and ii) exercise-training-induced FAO upregulation is largely attributable to muscle mitochondrial biogenesis. These long-standing concepts were developed prior to recent recognition that fatty acid entry into muscle occurs via a regulatable, sarcolemmal CD36-mediated mechanism. We examined the role of CD36 in muscle fuel selection under basal conditions, during a metabolic challenge (exercise), and after exercise-training. We also investigated whether CD36 overexpression, independent of mitochondrial changes, mimicked exercise-training-induced FAO upregulation. Under basal conditions CD36-KO vs WT mice displayed reduced fatty acid transport (-21%) and oxidation (-25%), intramuscular lipids (<-31%), and hepatic glycogen (-20%); but muscle glycogen, VO2max, and mitochondrial content and enzymes did not differ. In acutely exercised (78%VO2max) CD36-KO mice, fatty acid transport (-41%) and oxidation (-37%), and exercise duration (-44%) were reduced, while muscle and hepatic glycogen depletions were accelerated by 27-55%, revealing 2-fold greater carbohydrate use. Exercise-training increased mtDNA and β-HAD similarly in WT and CD36-KO muscles, but FAO was increased only in WT muscle (+90%). Comparable CD36 increases, induced by exercise-training (+44%) or by CD36-overexpression (+41%), increased FAO similarly (84-90%), either when mitochondrial biogenesis and FAO enzymes were upregulated (exercise-training) or when these were unaltered (CD36-overexpression). Thus, sarcolemmal CD36 has a key role in muscle fuel selection, exercise performance and training-induced muscle FAO adaptation, challenging long-held, views of mechanisms involved in acute and adaptive regulation of muscle FAO.

Keywords: CD36-KO mice, Fatty acids, Transport, Exercise, Training, Muscle, Transfection

O2k-Network Lab: CA Guelph Holloway GP


Labels: MiParea: Respiration, mt-Biogenesis;mt-density, mtDNA;mt-genetics, Exercise physiology;nutrition;life style 


Organism: Mouse  Tissue;cell: Skeletal muscle  Preparation: Permeabilized tissue 

Regulation: Fatty acid 


HRR: Oxygraph-2k