Leptin-induced transactivation of NPY gene promoter mediated by JAK1, JAK2 and STAT3 in the neural cell lines

Muraoka, Osamu; Xu, Bin; Tsurumaki, Tatsuru; Akira, Shizuo; Yamaguchi, Takashi; Handa, Hiroshi

doi:10.1016/s0197-0186(02)00160-2

Cited by 43 publications

(34 citation statements)

References 53 publications

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“…The dominant-negative transfections were performed using LipofectAMINE2000 (Invitrogen) according to the instructions of the manufacture. The cells were incubated for 24 h with 2.5 g of pEF-BOS (internal control), pWT-STAT3 (wild type of STAT3), or pDN-STAT3 (dominant-negative type of STAT3; kindly provided by Hiroshi Higuchi, Osaka University, Osaka, Japan) (Minami et al, 1996;Muraoka et al, 2003). Medium was then replaced with serum-free DMEM with 1% BSA for 2 h, after which the cells were treated with or without 10 Ϫ11 M leptin and incubated for 4 h before RNA isolation.…”

Section: Methodsmentioning

confidence: 99%

“…To further understand whether STAT proteins were important for the regulation of the NT gene by leptin, we used wild-type and dominant-negative STAT3 proteins [Y705F (Minami et al, 1996;Muraoka et al, 2003)] cloned into the mammalian expression vector, pEF-Bos, under the control of the elongation factor gene promoter. When we transiently transfected the three constructs into N-39 cells, we found that leptin treatment (10 Ϫ7 and 10 Ϫ11 M) was able to significantly induce NT gene expression with both the WT-STAT3 and mock pEF-Bos constructs, but NT induction was abolished after transfection of the DN-STAT3 construct (Fig.…”

Section: Localization Of Leptin Responsive Region Within the Nt Genementioning

confidence: 99%

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Anorexigenic Hormones Leptin, Insulin, and α-Melanocyte-Stimulating Hormone Directly Induce Neurotensin (NT) Gene Expression in Novel NT-Expressing Cell Models

Cui¹,

Cai²,

Belsham³

2005

J. Neurosci.

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Section: Methodsmentioning

confidence: 99%

Section: Localization Of Leptin Responsive Region Within the Nt Genementioning

confidence: 99%

Anorexigenic Hormones Leptin, Insulin, and α-Melanocyte-Stimulating Hormone Directly Induce Neurotensin (NT) Gene Expression in Novel NT-Expressing Cell Models

Cui¹,

Cai²,

Belsham³

2005

J. Neurosci.

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“…Consequently leptin-induced transactivation of the NPY gene was established in the neural cell lines that expressed the functional leptin receptor (23). Therefore, we further characterized the inhibitory mechanism of transcription of the NPY gene induced by leptin in vivo.…”

Section: Introductionmentioning

confidence: 99%

Transcriptional Regulation of Neuronal Genes and Its Effect on Neural Functions: Transcriptional Regulation of Neuropeptide Y Gene by Leptin and Its Effect on Feeding

2005

Self Cite

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Abstract. Leptin is an adipose tissue-derived secretory hormone that suppresses appetite by inhibition of neuropepeptide Y (NPY) gene expression in arcuate nucleus (ARC) in the hypothalamus. To investigate the transcriptional regulation of NPY gene by leptin, we carried out a luciferase assay using NPY gene promotor plasmid (NPY-luc) in NPY expressing cells such as N18TG2, NG108-15, and PC12 cells. In these cells, the NPY gene was transactivated by leptin through activation of leptin receptor. Leptin-induced transactivation was mediated through the 221-bp region of the NPY gene promotor, which possesses two putative STAT3 binding sites. To investigate the mechanism of in vivo suppression of NPY gene transcription in ARC by leptin, the effect of SOCS members on the leptin-induced transactivation of NPY gene was studied. In vivo SOCS2 and SOCS3 mRNAs were induced in mouse hypothalamus by leptin. Although leptin (125 ng / ml) induced significant increase in NPY gene transcriptional activity in mock-transfected cells, the leptin-induced NPY gene transcriptional activity was completely abolished in SOCS3-transfected cells. SOCS3 also suppressed the basal NPY gene transcription. These finding suggested that leptin inhibits NPY gene transcription in the hypothalamus in vivo and SOCS3 is a negative regulator of the NPY gene.

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“…Dysregulation of hepatic Xbp1s expression has been shown to be important in the pathogenesis of human NASH (Puri et al 2008). In addition, several studies have also demonstrated the important role of Socs3 in the pathogenesis of nonalcoholic steatohepatitis, regulating insulin sensitivity, leptin signaling, glucose metabolism, lipogenesis, and fatty liver Ihle 1995;Muraoka et al 2003;Kievit et al 2006;Howard et al 2004;Dittrich et al 2012;Sachithanandan et al 2010).…”

Section: Discussionmentioning

confidence: 99%

Identification of eQTLs for hepatic Xbp1 s and Socs3 gene expression in mice fed a high-fat, high caloric diet

Pasricha¹,

Anderson²,

Hall

et al. 2015

Z Gastroenterol

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Nonalcoholic fatty liver disease (NAFLD) is a highly prevalent form of human hepatic disease and feeding mice a high-fat, high-caloric (HFHC) diet is a standard model of NAFLD. To better understand the genetic basis of NAFLD, we conducted an expression quantitative trait locus (eQTL) analysis of mice fed a HFHC diet. Two-hundred sixty-five (A/J · C57BL/6J) F 2 male mice were fed a HFHC diet for 8 wk. eQTL analysis was utilized to identify genomic regions that regulate hepatic gene expression of Xbp1s and Socs3. We identified two overlapping loci for Xbp1s and Socs3 on Chr 1 (164.0-185.4 Mb and 174.4-190.5 Mb, respectively) and Chr 11 (41.1-73.1 Mb and 44.0-68.6 Mb, respectively), and an additional locus for Socs3 on Chr 12 (109.9-117.4 Mb). C57BL/6J-Chr 11 A/J / NaJ mice fed a HFHC diet manifested the A/J phenotype of increased Xbp1s and Socs3 gene expression (P , 0.05), whereas C57BL/6J-Chr 1 A/J / NaJ mice retained the C57BL/6J phenotype. In addition, we replicated the eQTLs on Chr 1 and Chr 12 (LOD scores $3.5) using mice from the BXD murine reference panel challenged with CCl 4 to induce chronic liver injury and fibrosis. We have identified overlapping eQTLs for Xbp1 and Socs3 on Chr 1 and Chr 11, and consomic mice confirmed that replacing the C57BL/6J Chr 11 with the A/J Chr 11 resulted in an A/J phenotype for Xbp1 and Socs3 gene expression. Identification of the genes for these eQTLs will lead to a better understanding of the genetic factors responsible for NAFLD and potentially other hepatic diseases.

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Leptin-induced transactivation of NPY gene promoter mediated by JAK1, JAK2 and STAT3 in the neural cell lines

Cited by 43 publications

References 53 publications

Anorexigenic Hormones Leptin, Insulin, and α-Melanocyte-Stimulating Hormone Directly Induce Neurotensin (NT) Gene Expression in Novel NT-Expressing Cell Models

Anorexigenic Hormones Leptin, Insulin, and α-Melanocyte-Stimulating Hormone Directly Induce Neurotensin (NT) Gene Expression in Novel NT-Expressing Cell Models

Transcriptional Regulation of Neuronal Genes and Its Effect on Neural Functions: Transcriptional Regulation of Neuropeptide Y Gene by Leptin and Its Effect on Feeding

Identification of eQTLs for hepatic Xbp1 s and Socs3 gene expression in mice fed a high-fat, high caloric diet

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