The <scp>JAK</scp>/<scp>STAT</scp> pathway in obesity and diabetes

Gurzov, Esteban Nicolas; Stanley, William J; Pappas, Evan G; Thomas, Helen; Gough, Daniel

doi:10.1111/febs.13709

Cited by 206 publications

(136 citation statements)

References 117 publications

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“…When leptin binds to the β-isoform of the leptin receptor, JAK2 is activated by autophosphorylation to phosphorylate tyrosine residues on the cytoplasmic tail of the receptor [30]. The enriched DEGs, such as STAT1 (signal transducer and activator of transcription 1), were upregulated and the leptin was downregulated in antagomiR34a-12h samples, which was in coincidence with the former research [29,30]. In addition, we found some notable pathways, including type I diabetes mellitus (ko04940), type II diabetes mellitus (ko04930), PPAR signaling pathway (ko03320), fatty acid biosynthesis (ko00061), fat digestion and absorption (ko04975), p53 signaling pathway (ko04115), insulin signaling pathway (ko04910), PI3K-Akt signaling pathway (ko04151), glycolysis/gluconeogenesis (ko00010) and insulin secretion (ko04911), were associated with these DEGs.…”

Section: Resultssupporting

confidence: 75%

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In Vivo Analysis of miR-34a Regulated Glucose Metabolism Related Genes in Megalobrama amblycephala

Miao

Lin

Huang

et al. 2018

IJMS

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The Megalobrama amblycephala (M. amblycephala) is one of the most important economic freshwater fish in China. The molecular mechanism under the glucose intolerance responses which affects the growth performance and feed utilization is still confused. miR-34a was reported as a key regulator in the glucose metabolism, but how did the miR-34a exert its function in the metabolism of glucose/insulin in M. amblycephala was still unclear. In this study, we intraperitoneally injected the miR-34a inhibitor (80 nmol/100 g body weight) into M. amblycephala (fed with high starch diet, 45% starch) for 12 h, and then analyzed the gene expression profiling in livers by RNA-seq. The results showed that miR-34a expression in M. amblycephala livers was inhibited by injection of miR-34a inhibitor, and a total of 2212 differentially expressed genes (DEGs) were dysregulated (including 1183 up- and 1029 downregulated DEGs). Function enrichment analysis of DEGs showed that most of them were enriched in the peroxisome proliferator-activated receptor (PPAR), insulin, AMP-activated protein kinase (AMPK) and janus kinase/signal transducers and activators of transcription (JAK/STAT) signaling pathways, which were all associated with the glucose/lipid metabolic and biosynthetic processes. In addition, we examined and verified the differential expression levels of some genes involved in AMPK signaling pathway by qRT-PCR. These results demonstrated that the inhibition of miR-34a might regulate glucose metabolism in M. amblycephala through downstream target genes.

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Section: Resultssupporting

confidence: 75%

“…It has been reported that the JAK-STAT pathway was responded to the metabolism in both type 1 diabetes (T1D) and T2D [29]. Obesity is a major risk factor for development of T2D, and lacking of leptin or the leptin receptor ( LepRb / ObRb ) will develop severe obesity and insulin resistance.…”

Section: Resultsmentioning

confidence: 99%

In Vivo Analysis of miR-34a Regulated Glucose Metabolism Related Genes in Megalobrama amblycephala

Miao

Lin

Huang

et al. 2018

IJMS

View full text Add to dashboard Cite

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“…STAT proteins are potent, conserved transcription factors. Seven STAT proteins have been identified as latent cytoplasmic transcription factors activated by tyrosine phosphorylation in response to cytokine and growth factor stimulation4142. STAT signaling plays an important role in the transfer of extracellular signals into the nucleus, resulting in transcriptional regulation, and is essential in the uncontrolled growth of cancer cells, angiogenesis and metastasis4344.…”

Section: Discussionmentioning

confidence: 99%

TMED3 promotes hepatocellular carcinoma progression via IL-11/STAT3 signaling

Zheng

Yang

Han

et al. 2016

Sci Rep

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Transmembrane p24 trafficking protein 3(TMED3) is a metastatic suppressor in colon cancer, but its function in the progression of hepatocellular carcinoma (HCC) is unknown. Here, we report that TMED3 was up-regulated in HCC and portal vein tumor thrombus. TMED3 up-regulation in HCC was significantly correlated with aggressive characteristics and predicted poor prognosis in HCC patients. TMED3 overexpression in HCC cell lines promoted cell migration and invasion. In contrast, TMED3 knockdown suppressed HCC metastasis both in vitro and in vivo. Gene microarray analysis revealed decreased IL-11 expression in TMED3-knockdown cells. We propose that TMED3 promotes HCC metastasis through IL-11/STAT3 signaling. Taken together, these findings demonstrate that TMED3 promotes HCC metastasis and is a potential prognostic biomarker in HCC.

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“…The JAK/STAT pathway contributes to β-cell dysfunction in both T1DM and T2DM [94]. It was recently reported that dysregulation of the JAK/STAT pathway contributes to the development of obesity and diabetes [94].…”

Section: Putative Signaling Mediating Diabetes-induced Microvasculmentioning

confidence: 99%

“…It was recently reported that dysregulation of the JAK/STAT pathway contributes to the development of obesity and diabetes [94]. Targeted deletion of STAT3 in the brain in a rodent model leads to the development of obesity and diabetes mimicking the phenotype of ob / ob or db / db mice; however, these data have not yet been confirmed in human studies [95].…”

Section: Putative Signaling Mediating Diabetes-induced Microvasculmentioning

confidence: 99%

Diabetic Microvascular Disease and Pulmonary Fibrosis: The Contribution of Platelets and Systemic Inflammation

Jagadapillai

Rane

Lin

et al. 2016

IJMS

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Diabetes is strongly associated with systemic inflammation and oxidative stress, but its effect on pulmonary vascular disease and lung function has often been disregarded. Several studies identified restrictive lung disease and fibrotic changes in diabetic patients and in animal models of diabetes. While microvascular dysfunction is a well-known complication of diabetes, the mechanisms leading to diabetes-induced lung injury have largely been disregarded. We described the potential involvement of diabetes-induced platelet-endothelial interactions in perpetuating vascular inflammation and oxidative injury leading to fibrotic changes in the lung. Changes in nitric oxide synthase (NOS) activation and decreased NO bioavailability in the diabetic lung increase platelet activation and vascular injury and may account for platelet hyperreactivity reported in diabetic patients. Additionally, the Janus kinase/signal transducer and activator of transcription (JAK/STAT) pathway has been reported to mediate pancreatic islet damage, and is implicated in the onset of diabetes, inflammation and vascular injury. Many growth factors and diabetes-induced agonists act via the JAK/STAT pathway. Other studies reported the contribution of the JAK/STAT pathway to the regulation of the pulmonary fibrotic process but the role of this pathway in the development of diabetic lung fibrosis has not been considered. These observations may open new therapeutic perspectives for modulating multiple pathways to mitigate diabetes onset or its pulmonary consequences.

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The JAK/STAT pathway in obesity and diabetes

Cited by 206 publications

References 117 publications

In Vivo Analysis of miR-34a Regulated Glucose Metabolism Related Genes in Megalobrama amblycephala

In Vivo Analysis of miR-34a Regulated Glucose Metabolism Related Genes in Megalobrama amblycephala

TMED3 promotes hepatocellular carcinoma progression via IL-11/STAT3 signaling

Diabetic Microvascular Disease and Pulmonary Fibrosis: The Contribution of Platelets and Systemic Inflammation

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