Insulin attenuates leptin-induced STAT3 tyrosine-phosphorylation in a hepatoma cell line.
Leptin, the 16 kDa protein product of the ob gene, is secreted by adipocytes. The long form leptin receptor (ObRb) is expressed at high levels in the hypothalamus, and regulates appetite and energy expenditure. The fact that serum concentration of leptin is correlated with body mass index (BMI) suggests reduced sensitivity to leptin. Even though hyperinsulinemia and hyperleptinemia could coexist in obese humans, little is known about the interaction of insulin and leptin. In this study, we examined the effect of insulin on leptin signaling using Huh 7 cells transiently transfected with ObRb cDNA. Insulin inhibits leptin-induced STAT3 phosphorylation in a time- and dose-dependent manner without affecting Janus tyrosine kinases (JAKs) JAK2 phosphorylation. Okadaic acid prevents the inhibitory effect of insulin on leptin-induced STAT3 activation.
Kuwahara
Hironaga
H
First Department of Internal Medicine, Division of Immunology, Endocrinology and Metabolism, Nagasaki University, 1-7-1 Sakamoto, 852-8501 Nagasaki, Japan.
Uotani
Shigeo
S
Abe
Takahiro
T
Degawa-Yamauchi
Mikako
M
Takahashi
Ryoko
R
Kita
Atsushi
A
Fujita
Naruhiro
N
Ohshima
Katuya
K
Sakamaki
Hiroyuki
H
Yamasaki
Hironori
H
Yamaguchi
Yoshihiko
Y
Eguchi
Katsumi
K
D000818:Animals; D006528:Carcinoma, Hepatocellular / Q000378:metabolism*; D045744:Cell Line, Tumor; D018076:DNA, Complementary / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000737:chemistry / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D006801:Humans; D007328:Insulin / Q000494:pharmacology*; D053614:Janus Kinase 2; D020738:Leptin / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D008113:Liver Neoplasms / Q000378:metabolism*; D051379:Mice; D019319:Okadaic Acid / Q000494:pharmacology; D010766:Phosphorylation; D011485:Protein Binding; D017027:Protein Tyrosine Phosphatases / Q000378:metabolism; D011505:Protein-Tyrosine Kinases / Q000378:metabolism; D011518:Proto-Oncogene Proteins; D011972:Receptor, Insulin / Q000378:metabolism; D011956:Receptors, Cell Surface / Q000235:genetics; D054411:Receptors, Leptin; D050796:STAT3 Transcription Factor; D013997:Time Factors; D015534:Trans-Activators / Q000737:chemistry / Q000378:metabolism*; D014443:Tyrosine / Q000378:metabolism
D018076:DNA, Complementary; D004268:DNA-Binding Proteins; D007328:Insulin; C515448:LEPR protein, human; D020738:Leptin; D011518:Proto-Oncogene Proteins; D011956:Receptors, Cell Surface; D054411:Receptors, Leptin; D050796:STAT3 Transcription Factor; C494086:STAT3 protein, human; C494087:Stat3 protein, mouse; D015534:Trans-Activators; C515447:leptin receptor, mouse; D019319:Okadaic Acid; D014443:Tyrosine; D011505:Protein-Tyrosine Kinases; D011972:Receptor, Insulin; C507924:JAK2 protein, human; C507926:Jak2 protein, mouse; D053614:Janus Kinase 2; D017027:Protein Tyrosine Phosphatases