A null mutation in H-FABP only partially inhibits skeletal muscle fatty acid metabolism

Binas, Bert; Han, Xiaoxia; Erol, Erdal; Luiken, Joost J. F. P.; Glatz, Jan F. C.; Dyck, David J.; Motazavi, Rafat; Adihetty, Peter J.; Hood, David A.; Bonen, Arend

doi:10.1152/ajpendo.00060.2003

Cited by 37 publications

(33 citation statements)

References 34 publications

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“…Previous work using isolated myocytes from the H-FABP gene-ablated mice demonstrated a 45% reduction in 16:0 uptake (2). Other studies using giant vesicles made from isolated muscle tissue demonstrate a partial reduction in vesicle fatty acid uptake in H-FABP gene-ablated mice (48,49). However, this reduction was much less than what was observed in isolated myocytes or in our results presented here.…”

Section: Discussioncontrasting

confidence: 82%

Heart Fatty Acid Uptake Is Decreased in Heart Fatty Acid-binding Protein Gene-ablated Mice

Murphy

Barceló‐Coblijn

Binas

et al. 2004

Journal of Biological Chemistry

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Section: Discussioncontrasting

confidence: 82%

Heart Fatty Acid Uptake Is Decreased in Heart Fatty Acid-binding Protein Gene-ablated Mice

Murphy

Barceló‐Coblijn

Binas

et al. 2004

Journal of Biological Chemistry

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“…Medium-chain acyl-CoA dehydrogenase (MCAD) is a mitochondrial enzyme that catalyzes the initial reaction in the FA ␤-oxidation cycle (34,35). Heart type FA-binding protein (H-FABP) is a cytosolic protein important in the intracellular transport of FAs with effects on triglyceride accumulation and oxidation (36)(37)(38). Fatty acid transport protein 1 (FATP-1) is an integral plasma membrane protein involved with FA uptake into the cell, and which also has been reported to have acyl-CoA synthase activity (39)(40)(41).…”

Section: Resultsmentioning

confidence: 99%

Mechanisms mediating insulin resistance in transgenic mice overexpressing mouse apolipoprotein A-II

Castellani

Gargalovic

Febbraio

et al. 2004

Journal of Lipid Research

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We previously demonstrated that transgenic mice overexpressing mouse apolipoprotein A-II (apoA-II) exhibit several traits associated with the insulin resistance (IR) syndrome, including increased atherosclerosis, hypertriglyceridemia, obesity, and IR. The skeletal muscle appeared to be the insulin-resistant tissue in the apoA-II transgenic mice. We now demonstrate a decrease in FA oxidation in skeletal muscle of apoA-II transgenic mice, consistent with reports that decreased skeletal muscle FA oxidation is associated with increased skeletal muscle triglyceride accumulation, skeletal muscle IR, and obesity. The decrease in FA oxidation is not due to decreased carnitine palmitoyltransferase 1 activity, because oxidation of palmitate and octanoate were similarly decreased. Alterations in both glucose and lipid metabolism are two consistent features of the insulin resistance (IR) syndrome) (1, 2). Several studies have demonstrated that primary changes in FA metabolism can lead to IR (3-8). Although much has been learned about the insulin signaling pathways and the metabolism of both glucose and FAs, the underlying cause of most cases of IRS and type 2 diabetes is unknown (9, 10). Whether primary defects in FA metabolism or glucose metabolism underlie the majority of human cases of IRS and type 2 diabetes remains to be determined.Studies using genetically altered mice have demonstrated that both the scavenger receptor CD36 and the HDL-associated protein apolipoprotein A-II (apoA-II) alter FA metabolism and IR (11-16). Furthermore, HDL is a ligand for the CD36 receptor, which raises the possibility of an HDL-CD36 interaction that affects FA metabolism (15). Mice with a null mutation for apoA-II exhibit increased sensitivity to insulin, with decreased plasma concentrations of triglycerides, FFA, and glucose (11). We previously demonstrated that increasing plasma concentrations of mouse apoA-II in transgenic mice produced several aspects of the IR syndrome including hypertriglyceridemia, obesity, and IR, as well as increased atherosclerotic lesion development (12,(17)(18)(19). The skeletal muscle appeared to be the insulin-resistant tissue in the apoA-II transgenic mice, whereas the liver and adipose tissue in the apoA-II trangenic mice appeared to respond normally (12). Compared with control mice, isolated soleus muscles from the apoA-II transgenic mice exhibited decreased glucose uptake and increased triglyceride accumulation (12). We hypothesize that primary alterations in FA metabolism in skeletal muscle initiate IR and promote the development of obesity. In the present study, we demonstrate that FA oxidation is reduced in the skeletal muscle of apoA-II transgenic mice, which could initiate the metabolic events that lead to skeletal muscle IR. We also placed the apoA-II transgene onto a CD36 knockout background and demonstrated that plasma triglyceride and insulin concentrations are not markedly different in the apoA-II transgenic mice, whether or Abbreviations: apoA-II, apolipoprotein A-II; CPT-1, carnitin...

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“…For these purposes, acid-soluble 14 C products in hindlimb muscles were obtained during the extraction of the lipids from the hindlimb muscles. This method has been widely used in isolated muscles (3,5,9,18,19,37,44) and in studies with fatty acid oxidation by isolated mitochondria (10,28).…”

Section: Co2 Productionmentioning

confidence: 99%

A null mutation in skeletal muscle FAT/CD36 reveals its essential role in insulin- and AICAR-stimulated fatty acid metabolism

Bonen¹,

Han²,

Habets³

et al. 2007

American Journal of Physiology-Endocrinology and Metabolism

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Bonen A, Han X-X, Habets DD, Febbraio M, Glatz JF, Luiken JJ. A null mutation in skeletal muscle FAT/CD36 reveals its essential role in insulin-and AICAR-stimulated fatty acid metabolism. Am J Physiol Endocrinol Metab 292: E1740 -E1749, 2007. First published January 30, 2007; doi:10.1152/ajpendo.00579.2006.-Fatty acid translocase (FAT)/CD36 is involved in regulating the uptake of long-chain fatty acids into muscle cells. However, the contribution of FAT/CD36 to fatty acid metabolism remains unknown. We examined the role of FAT/CD36 on fatty acid metabolism in perfused muscles (soleus and red and white gastrocnemius) of wild-type (WT) and FAT/CD36 null (KO) mice. In general, in muscles of KO mice, 1) insulin sensitivity and 5-aminoimidazole-4-carboxamide-1-␤-Dribofuranoside (AICAR) sensitivity were normal, 2) key enzymes involved in fatty acid oxidation were altered minimally or not at all, and 3) except for an increase in soleus muscle FATP1 and FATP4, these fatty acid transporters were not altered in red and white gastrocnemius muscles, whereas plasma membrane-bound fatty acid binding protein was not altered in any muscle. In KO muscles perfused under basal conditions (i.e., no insulin, no AICAR), rates of hindquarter fatty acid oxidation were reduced by 26%. Similarly, in oxidative but not glycolytic muscles, the basal rates of triacylglycerol esterification were reduced by 40%. When muscles were perfused with insulin, the net increase in fatty acid esterification was threefold greater in the oxidative muscles of WT mice compared with the oxidative muscles in KO mice. With AICAR-stimulation, the net increase in fatty acid oxidation by hindquarter muscles was 3.7-fold greater in WT compared with KO mice. In conclusion, the present studies demonstrate that FAT/CD36 has a critical role in regulating fatty acid esterification and oxidation, particularly during stimulation with insulin or AICAR.perfusion; palmitate; esterification; oxidation; fatty transport proteins 1 and 2; plasma membrane-bound fatty acid binding protein; 5-amino-imidazole-4-carboxamide-1-␤-D-ribofuranoside IN RECENT YEARS it has been established that fatty acid transport into metabolically active tissues such as heart and skeletal muscle occurs, in part, via a protein-mediated process (4, 7-9, 32, 33). Although a number of fatty acid transporters have been identified, it appears that fatty acid translocase (FAT)/CD36 and plasma membrane-bound fatty acid binding protein (FABPpm) are two key fatty acid transporters. Upregulation of FAT/CD36 and FABPpm, either after 7 days of chronic muscle contraction or after exposure of cardiac myocytes to insulin or 5-aminoimidazole-4-carboxamide-1-␤-D-ribofuranoside (AICAR), increases the rates of fatty acid transport (1,5,11,13,27). Conversely, when FAT/CD36 and FABPpm are concurrently downregulated, the rates of fatty acid transport into resting muscle are decreased (27, 44). The content of plasmalemmal FAT/CD36, but not FABPpm, is increased in insulin-resistant skeletal muscle, and this correlates with in...

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A null mutation in H-FABP only partially inhibits skeletal muscle fatty acid metabolism

Cited by 37 publications

References 34 publications

Heart Fatty Acid Uptake Is Decreased in Heart Fatty Acid-binding Protein Gene-ablated Mice

Heart Fatty Acid Uptake Is Decreased in Heart Fatty Acid-binding Protein Gene-ablated Mice

Mechanisms mediating insulin resistance in transgenic mice overexpressing mouse apolipoprotein A-II

A null mutation in skeletal muscle FAT/CD36 reveals its essential role in insulin- and AICAR-stimulated fatty acid metabolism

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