Key role of the ERK1/2 MAPK pathway in the transcriptional regulation of the Stearoyl-CoA Desaturase (SCD1) gene expression in response to leptin

Molecular and Cellular Endocrinology
Daniel MauvoisinCatherine Mounier

Abstract

Stearoyl-CoA Desaturase-1 (SCD1) is the rate limiting enzyme catalyzing the synthesis of monounsaturated fatty acids. Variation of SCD1 activity and the ratio of saturated to unsaturated fatty acids have been implicated in a variety of diseases including obesity, type II diabetes and cancers. In liver, many factors regulate SCD1 expression including dietary and hormonal factors such as insulin and leptin. We previously showed in hepatic cells that insulin acts through the PI3K and mTOR pathways to upregulate SCD1 expression. In the present study, using HepG2 cells, we characterized the signaling pathway mediating the leptin inhibitory response on SCD1 gene expression. We showed that leptin inhibits SCD1 at the transcriptional level. Inhibition of the ERK1/2 MAPK pathway with the PD98059 reverses the effect of leptin on SCD1 expression. Our data also demonstrated that the effect of leptin is entirely independent of the effect of insulin. Using the pharmaceutical inhibitors Ag490 and SL0101, we showed that the inhibitory effect of leptin is also mediated by the Janus Kinase 2 (Jak2) and p90RSK. EMSA and transfection experiments suggest a key role for the Sp1 transcription factor, which in turn may compete for the binding of other...Continue Reading

Citations

Dec 5, 2012·Breast Cancer Research and Treatment·Ashley M HolderFunda Meric-Bernstam
Nov 17, 2012·Nutrition & Diabetes·M Caron-JobinC Mounier
Nov 10, 2010·Molecular Medicine·Sara García-SerranoEduardo García-Fuentes
May 23, 2014·Obesity Research & Clinical Practice·Emiko SaitoYohei Kitamura
Aug 18, 2010·Biochimie·Daniel Mauvoisin, Catherine Mounier
Aug 16, 2016·Endocrinology and Metabolism Clinics of North America·Georgios A TriantafyllouChristos S Mantzoros
Oct 22, 2016·Biochimica Et Biophysica Acta·R Ariel Igal
Dec 20, 2011·Cellular Physiology and Biochemistry : International Journal of Experimental Cellular Physiology, Biochemistry, and Pharmacology·Lauren M CornallAndrew J McAinch
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Jun 12, 2012·The Journal of Immunology : Official Journal of the American Association of Immunologists·Peter MancusoMarc Peters-Golden
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Nov 22, 2020·Molecular Aspects of Medicine·Elena PiccininAntonio Moschetta
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