Signal transducer and activator of transcription 3 (STAT3) regulates adipocyte differentiation via peroxisome‐proliferator‐activated receptor γ (PPARγ)

Wang, Dongmei; Zhou, Yiran; Lei, Weiwei; Zhang, Kehua; Shi, Jian; Ying, Hanjie; Gao, Shu; Song, Jianguo

doi:10.1042/bc20090070

Cited by 85 publications

(66 citation statements)

References 49 publications

(61 reference statements)

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“…It is worth mentioning that BBR is known to regulate glucose handling and lipid metabolism in hepatocytes and adipocytes (36,40,41). Given that STAT3 is a key transcription factor in these processes (42,43) and our novel findings of BBR regulation of STAT3, it raises the possibility that BBR regulates metabolism through the JAK/STAT3 cascade, which may provide new therapeutic avenues to regulate glucose and lipid homeostasis.…”

Section: Discussionmentioning

confidence: 99%

Regulation of Th1 and Th17 Cell Differentiation and Amelioration of Experimental Autoimmune Encephalomyelitis by Natural Product Compound Berberine

Qin

Guo

Wan

et al. 2010

The Journal of Immunology

103

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Berberine (BBR), an isoquinoline alkaloid derived from plants, is widely used as an anti-inflammatory remedy in traditional Chinese medicine. In this study, we showed that BBR was efficacious in the amelioration of experimental autoimmune encephalomyelitis (EAE) through novel regulatory mechanisms involving pathogenic Th1 and Th17 cells. BBR inhibited differentiation of Th17 cells and, to a lesser degree, Th1 cells through direct actions on the JAK/STAT pathway, whereas it had no effect on the relative number of CD4+Foxp3+ regulatory T cells. In addition, BBR indirectly influenced Th17 and Th1 cell functions through its effect on the expression and function of costimulatory molecules and the production of IL-6, which was attributable to the inhibition of NF-κB activity in CD11b+ APCs. BBR treatment completely abolished the encephalitogenicity of MOG35–55-reactive Th17 cells in an adoptive transfer EAE model, and the same treatment significantly inhibited the ability of MOG35–55-reactive Th1 cells to induce EAE. This study provides new evidence that natural compounds, such as BBR, are of great value in the search for novel anti-inflammatory agents and therapeutic targets for autoimmune diseases.

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Section: Discussionmentioning

confidence: 99%

Regulation of Th1 and Th17 Cell Differentiation and Amelioration of Experimental Autoimmune Encephalomyelitis by Natural Product Compound Berberine

Qin

Guo

Wan

et al. 2010

The Journal of Immunology

103

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“…S1D). The Jak family of kinases have been implicated in the differentiation of white preadipocyte cell lines, particularly in the induction of the master regulators Cebpb/Cebpd and Pparg (15,16,47). Beyond this, only limited information is available on the downstream target genes in this context (14).…”

Section: Discussionmentioning

confidence: 99%

Jak-TGFβ cross-talk links transient adipose tissue inflammation to beige adipogenesis

et al. 2018

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The transient activation of inflammatory networks is required for adipose tissue remodeling including the "browning" of white fat in response to stimuli such as 3-adrenergic receptor activation. In this process, white adipose tissue acquires thermogenic characteristics through the recruitment of so-called beige adipocytes. We investigated the downstream signaling pathways impinging on adipocyte progenitors that promote de novo formation of adipocytes. We showed that the Jak family of kinases controlled TGF signaling in the adipose tissue microenvironment through Stat3 and thereby adipogenic commitment, a function that was required for beige adipocyte differentiation of murine and human progenitors. Jak/Stat3 inhibited TGF signaling to the transcription factors Srf and Smad3 by repressing local Tgfb3 and Tgfb1 expression before the core transcriptional adipogenic cascade was activated. This pathway cross-talk was triggered in stromal cells by ATGL-dependent adipocyte lipolysis and a transient wave of IL-6 family cytokines at the onset of adipose tissue remodeling induced by 3-adrenergic receptor stimulation. Our results provide insight into the activation of adipocyte progenitors and are relevant for the therapeutic targeting of adipose tissue inflammatory pathways.

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“…STAT3 is known to express in human adipocytes (Harp et al 2001), mouse adipocytes (Deng et al 2006), and mouse 3T3-L1 cells (Stephens et al 1996, Wang et al 2010 to regulate adipogenesis. Activation of STAT3 activity leads to the induction of adipogenesis (Stephens et al 1996, Harp et al 2001, Wang et al 2010) and inhibition of STAT3 activity by inhibitors or siRNA resulted in suppression of adipocyte differentiation (Deng et al 2006, Wang et al 2010. In line with these findings, we found that S3I-201 treated HFDThrb PV/PV Pten C/K mice markedly decreased adipocyte cell size (Fig.…”

Section: Discussionmentioning

confidence: 99%

Inhibition of STAT3 activity delays obesity-induced thyroid carcinogenesis in a mouse model

Park

Han

Zhao

et al. 2015

Endocrine-Related Cancer

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Compelling epidemiologic studies indicate that obesity is a risk factor for many human cancers, including thyroid cancer. In recent decades, the incidence of thyroid cancer has dramatically increased along with a marked rise in obesity prevalence. We previously demonstrated that a high fat diet (HFD) effectively induced the obese phenotype in a mouse model of thyroid cancer (Thrb PV/PV Pten C/K mice). Moreover, HFD activates the STAT3 signal pathway to promote more aggressive tumor phenotypes. The aim of the present study was to evaluate the effect of S3I-201, a specific inhibitor of STAT3 activity, on HFD-induced aggressive cancer progression in the mouse model of thyroid cancer. WT and Thrb PV/PV Pten C/K mice were treated with HFD together with S3I-201 or vehicle-only as controls. We assessed the effects of S3I-201 on HFD-induced thyroid cancer progression, the leptin-JAK2-STAT3 signaling pathway, and key regulators of epithelial-mesenchymal transition (EMT). S3I-201 effectively inhibited HFD-induced aberrant activation of STAT3 and its downstream targets to markedly inhibit thyroid tumor growth and to prolong survival. Decreased protein levels of cyclins D1 and B1, cyclin dependent kinase 4 (CDK4), CDK6, and phosphorylated retinoblastoma protein led to the inhibition of tumor cell proliferation in S3I-201-treated Thrb PV/PV Pten C/K mice. Reduced occurrence of vascular invasion and blocking of anaplasia and lung metastasis in thyroid tumors of S3I-201-treated Thrb PV/PV Pten C/K mice were mediated via decreased expression of vimentin and matrix metalloproteinases, two key effectors of EMT. The present findings suggest that inhibition of the STAT3 activity would be a novel treatment strategy for obesity-induced thyroid cancer.

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Signal transducer and activator of transcription 3 (STAT3) regulates adipocyte differentiation via peroxisome‐proliferator‐activated receptor γ (PPARγ)

Cited by 85 publications

References 49 publications

Regulation of Th1 and Th17 Cell Differentiation and Amelioration of Experimental Autoimmune Encephalomyelitis by Natural Product Compound Berberine

Regulation of Th1 and Th17 Cell Differentiation and Amelioration of Experimental Autoimmune Encephalomyelitis by Natural Product Compound Berberine

Jak-TGFβ cross-talk links transient adipose tissue inflammation to beige adipogenesis

Inhibition of STAT3 activity delays obesity-induced thyroid carcinogenesis in a mouse model

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