RGD Reference Report - Chronic leptin administration decreases fatty acid uptake and fatty acid transporters in rat skeletal muscle. - Rat Genome Database

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Chronic leptin administration decreases fatty acid uptake and fatty acid transporters in rat skeletal muscle.

Authors: Steinberg, GR  Dyck, DJ  Calles-Escandon, J  Tandon, NN  Luiken, JJ  Glatz, JF  Bonen, A 
Citation: Steinberg GR, etal., J Biol Chem 2002 Mar 15;277(11):8854-60.
RGD ID: 619548
Pubmed: PMID:11729182   (View Abstract at PubMed)
DOI: DOI:10.1074/jbc.M107683200   (Journal Full-text)

Chronic leptin administration reduces triacylglycerol content in skeletal muscle. We hypothesized that chronic leptin treatment, within physiologic limits, would reduce the fatty acid uptake capacity of red and white skeletal muscle due to a reduction in transport protein expression (fatty acid translocase (FAT/CD36) and plasma membrane-associated fatty acid-binding protein (FABPpm)) at the plasma membrane. Female Sprague-Dawley rats were infused for 2 weeks with leptin (0.5 mg/kg/day) using subcutaneously implanted miniosmotic pumps. Control and pair-fed animals received saline-filled implants. Leptin levels were significantly elevated (approximately 4-fold; p < 0.001) in treated animals, whereas pair-fed treated animals had reduced serum leptin levels (approximately -2-fold; p < 0.01) relative to controls. Palmitate transport rates into giant sarcolemmal vesicles were reduced following leptin treatment in both red (-45%) and white (-84%) skeletal muscle compared with control and pair-fed animals (p < 0.05). Leptin treatment reduced FAT mRNA (red, -70%, p < 0.001; white, -48%, p < 0.01) and FAT/CD36 protein expression (red, -32%; p < 0.05) in whole muscle homogenates, whereas FABPpm mRNA and protein expression were unaltered. However, in leptin-treated animals plasma membrane fractions of both FAT/CD36 and FABPpm protein expression were significantly reduced in red (-28 and -34%, respectively) and white (-44 and -56%, respectively) muscles (p < 0.05). Across all experimental treatments and muscles, palmitate uptake by giant sarcolemmal vesicles was highly correlated with the plasma membrane FAT/CD36 protein (r = 0.88, p < 0.01) and plasma membrane FABPpm protein (r = 0.94, p < 0.01). These studies provide the first evidence that protein-mediated long chain fatty acid transport is subject to long term regulation by leptin.

Gene Ontology Annotations    Click to see Annotation Detail View

Biological Process
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
fatty acid metabolic process  IDA 619548; 619548 RGD 

Molecular Function
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
fatty acid binding  TAS 619548 RGD 

Objects Annotated

Genes (Rattus norvegicus)
Cd36  (CD36 molecule)
Fabp2  (fatty acid binding protein 2)


Additional Information