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Long‐chain fatty acid uptake by skeletal muscle is impaired in homozygous, but not heterozygous, heart‐type‐FABP null mice
Author(s) -
Luiken J. J. F. P.,
Koonen D. P. Y.,
Coumans W. A.,
Pelsers M. M. A. L.,
Binas B.,
Bonen A.,
Glatz J. F. C.
Publication year - 2003
Publication title -
lipids
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.601
H-Index - 120
eISSN - 1558-9307
pISSN - 0024-4201
DOI - 10.1007/s11745-003-1089-6
Subject(s) - fatty acid binding protein , skeletal muscle , heart type fatty acid binding protein , medicine , endocrinology , cd36 , wild type , biology , myocyte , chemistry , lipotoxicity , biochemistry , receptor , gene , mutant , insulin , insulin resistance
Previous studies with cardiac myocytes from homozygous heart‐type fatty acid (FA)‐binding protein (H‐FABP) −/− mice have indicated that this intracellular: receptor protein for long‐chain FA is involved in the cellular uptake of these substrates. Based on the knowledge that muscle FA uptake is a process highly sensitive to regulation by hormonal and mechanical stimuli, we studied whether H‐FABP would play a role in this regulation. A suitable model system to answer this question is provided by H‐FABP +/− mice, because in hindlimb muscles the content of H‐FABP was measured to be 34% compared to wild‐type mice. In these H‐FABP +/− skeletal muscles, just as in H‐FABP −/− muscles, contents of FA transporters, i.e., 43‐kDa FABPpm and 88‐kDa FAT/CD36, were similar compared to wild‐type muscles, excluding possible compensatory mech‐anisms at the sarcolemmal level. Palmitate uptake rates were measured in giant vesicles prepared from hindlimb muscles of H‐FABP −/− , H‐FABP +/− and H‐FABP +/+ mice. For comparison, giant vesicles were isolated from liver, the tissue of which expresses a distinct type of FABP (i.e., L‐FABP). Whereas in H‐FABP −/− skeletal muscle FA uptake was reduced by 42–45%, FA uptake by H‐FABP +/− skeletal muscle was not different from that in wild‐type mice. In contrast, in liver from H‐FABP −/− and from H‐FABP +/− mice, FA uptake was not altered compared to wild‐type animals, indicating that changes in FA uptake are restricted to H‐FABP expressing tissues. It is concluded that H‐FABP plays an important, yet merely permissive, role in FA uptake into muscle tissues.