In vivo leptin infusion impairs insulin and leptin signalling in liver and hypothalamus.
Leptin resistance contributes to the pathogenesis of common obesity related metabolic diseases, including insulin resistance. However, the relationship between leptin and insulin resistance is not clearly established. Here, we show that induced hyperleptinemia by leptin infusion alters insulin signalling in rat liver. Leptin infusion clearly reduced the insulin or leptin dependent IRS-1/IRS-2 association to p85 regulatory subunit of PI 3-kinase. Leptin infusion also abolished STAT-3 phosphorylation in response to insulin or leptin and similar results were obtained for MAP-kinase phosphorylation. Hypothalamic leptin resistance was also induced by leptin infusion since leptin was unable to induce STAT-3 phosphorylation. These results provide evidence that induced hyperleptinemia can contribute to the onset of insulin resistance at least at the hepatic level.
Benomar
Yacir
Y
Neuroendocrinologie Moléculaire de la Prise Alimentaire INRA, Université Paris XI, IBAIC, Bat447, 91405 Orsay, France.
Wetzler
Sandrine
S
Larue-Achagiotis
Christiane
C
Djiane
Jean
J
Tomé
Daniel
D
Taouis
Mohammed
M
D000818:Animals; D001835:Body Weight; D004435:Eating; D007031:Hypothalamus / Q000187:drug effects* / Q000378:metabolism; D007263:Infusions, Parenteral; D007328:Insulin / Q000378:metabolism* / Q000494:pharmacology; D055504:Insulin Receptor Substrate Proteins; D007333:Insulin Resistance; D047908:Intracellular Signaling Peptides and Proteins; D020738:Leptin / Q000008:administration & dosage / Q000097:blood / Q000378:metabolism* / Q000494:pharmacology*; D008099:Liver / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D019869:Phosphatidylinositol 3-Kinases / Q000737:chemistry / Q000378:metabolism; D010750:Phosphoproteins / Q000378:metabolism; D010766:Phosphorylation / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D050796:STAT3 Transcription Factor / Q000378:metabolism; D012756:Sheep; D015398:Signal Transduction / Q000187:drug effects*
D007328:Insulin; D055504:Insulin Receptor Substrate Proteins; D047908:Intracellular Signaling Peptides and Proteins; C526296:Irs1 protein, rat; C526299:Irs2 protein, rat; D020738:Leptin; D010750:Phosphoproteins; D050796:STAT3 Transcription Factor; D019869:Phosphatidylinositol 3-Kinases; D020928:Mitogen-Activated Protein Kinases