Fatty acids inhibit leptin signalling in BRIN-BD11 insulinoma cells.
The effect of treatment with a 0.03% fatty acid (FA) cocktail on leptin-receptor-mediated STAT (signal transducers and activators of transcription) activation in the rat insulinoma cell line BRIN-BD11 was investigated. Leptin (10 nM) stimulated the tyrosine phosphorylation of STAT3 and STAT5b. Acute treatment with FAs prevented leptin-stimulated STAT3 tyrosine phosphorylation and significantly raised basal STAT5 phosphorylation. A chronic treatment (5 days) of BRIN-BD11 cells with FAs similarly attenuated leptin-stimulated STAT tyrosine phosphorylation. Chronic FA treatment also attenuated prolactin-stimulated STAT5b tyrosine phosphorylation but not interleukin-6-stimulated STAT3 tyrosine phosphorylation, suggesting that the effect is receptor/ligand specific. TaqMan analysis of gene expression following chronic FA treatment showed neither a decrease in the amount of leptin receptor (Ob-R) mRNA, nor an increase in the negative regulators of STAT signalling, SOCS3 (suppressors of cytokine signalling) or cytokine inducible sequence (CIS). These data demonstrate that FAs modulate leptin and prolactin signalling in beta-cells, implying that high levels of circulating FAs present in obese individuals affect the action of selective cytokines in beta-cell function.
Department of Vascular Biology, SmithKline Beecham Pharmaceuticals, New Frontiers Science Park, Harlow, Essex, UK.
C P
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Briscoe
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Hanif
J R
JR
Arch
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Tadayyon
D000818:Animals; D015153:Blotting, Western; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism*; D004268:DNA-Binding Proteins / Q000378:metabolism*; D005227:Fatty Acids / Q000494:pharmacology*; D017874:Immediate-Early Proteins / Q000378:metabolism; D007340:Insulinoma; D015850:Interleukin-6 / Q000378:metabolism; D007515:Islets of Langerhans / Q000187:drug effects* / Q000378:metabolism; D020738:Leptin / Q000378:metabolism*; D008894:Milk Proteins; D010766:Phosphorylation / Q000187:drug effects; D011233:Precipitin Tests; D011388:Prolactin / Q000378:metabolism; D020033:Protein Isoforms; D011506:Proteins / Q000378:metabolism; D051381:Rats; D011956:Receptors, Cell Surface; D054411:Receptors, Leptin; D012097:Repressor Proteins; D050796:STAT3 Transcription Factor; D050799:STAT5 Transcription Factor; D015398:Signal Transduction / Q000187:drug effects* / Q000502:physiology; D000071223:Suppressor of Cytokine Signaling 3 Protein; D050826:Suppressor of Cytokine Signaling Proteins; D015534:Trans-Activators / Q000378:metabolism*; D014157:Transcription Factors; D014407:Tumor Cells, Cultured; D014443:Tyrosine / Q000378:metabolism
D002352:Carrier Proteins; D004268:DNA-Binding Proteins; D005227:Fatty Acids; D017874:Immediate-Early Proteins; D015850:Interleukin-6; D020738:Leptin; D008894:Milk Proteins; D011388:Prolactin; D020033:Protein Isoforms; D011506:Proteins; D011956:Receptors, Cell Surface; D054411:Receptors, Leptin; D012097:Repressor Proteins; D050796:STAT3 Transcription Factor; D050799:STAT5 Transcription Factor; D000071223:Suppressor of Cytokine Signaling 3 Protein; D050826:Suppressor of Cytokine Signaling Proteins; D015534:Trans-Activators; D014157:Transcription Factors; D014443:Tyrosine; C491410:Socs3 protein, rat; C494088:Stat3 protein, rat; C494097:Stat5b protein, rat