Hypoxia-inducible Factor 1α Regulates a SOCS3-STAT3-Adiponectin Signal Transduction Pathway in Adipocytes

Jiang, Changtao; Kim, Junghwan; Li, Fēi; Qu, Aijuan; Гаврилова, Оксана; Shah, Yatrik M.; Gonzalez, Frank J.

doi:10.1074/jbc.m112.426338

Cited by 62 publications

(54 citation statements)

References 51 publications

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“…Recent data showed that adiponectin-deficient mice developed vascular remodeling, inflammation and pulmonary hypertension, confirming the influence of this adipokine on the vasculature [28]. Finally, in accordance with our results, in vitro studies showed that hypoxia (and more specifically the activation of the hypoxia inducible factor-1 α) suppresses adiponectin expression by adipocytes [29]. Nonetheless, other studies conducted in humans had not detected a reduction in adiponectin after acute HH.…”

Section: Discussionsupporting

confidence: 91%

Vascular reactivity and biomarkers of endothelial function in healthy subjects exposed to acute hypobaric hypoxia

Iglesias

Rosso

Vainstein

et al. 2015

Clinical Biochemistry

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Section: Discussionsupporting

confidence: 91%

Vascular reactivity and biomarkers of endothelial function in healthy subjects exposed to acute hypobaric hypoxia

Iglesias

Rosso

Vainstein

et al. 2015

Clinical Biochemistry

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“…A study found that HIF-1α inhibits production of adiponectin. When adipocyte-specific HIF-1α knock-out mice were fed a high-fat diet for 7 weeks, they displayed high levels of adiponectin mRNA; meanwhile, control mice showed significantly low levels of adiponectin mRNA 74. These conditions could induce metabolic alteration in the brain and initiate pathology of AD.…”

Section: Alzheimer's Disease: Reduced Levels Of Adiponectin Induced Bmentioning

confidence: 99%

Metabolism-Centric Overview of the Pathogenesis of Alzheimer's Disease

2017

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Alzheimer's disease (AD) is a degenerative brain disease and the most common cause of dementia. AD is characterized by the extracellular amyloid beta (Aβ) plaques and intraneuronal deposits of neurofibrillary tangles (NFTs). Recently, as aging has become a familiar phenomenon around the world, patients with AD are increasing in number. Thus, many researchers are working toward finding effective therapeutics for AD focused on Aβ hypothesis, although there has been no success yet. In this review paper, we suggest that AD is a metabolic disease and that we should focus on metabolites that are affected by metabolic alterations to find effective therapeutics for AD. Aging is associated with not only AD but also obesity and type 2 diabetes (T2DM). AD, obesity, and T2DM share demographic profiles, risk factors, and clinical and biochemical features in common. Considering AD as a kind of metabolic disease, we suggest insulin, adiponectin, and antioxidants as mechanistic links among these diseases and targets for AD therapeutics. Patients with AD show reduced insulin signal transductions in the brain, and intranasal injection of insulin has been found to have an effect on AD treatment. In addition, adiponectin is decreased in the patients with obesity and T2DM. This reduction induces metabolic dysfunction both in the body and the brain, leading to AD pathogenesis. Oxidative stress is known to be induced by Aβ and NFTs, and we suggest that oxidative stress caused by metabolic alterations in the body induce brain metabolic alterations, resulting in AD.

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“…Similarly, in neural stem cells, KLF4 transcriptionally activates cytokine receptors and JAK3, leading to STAT3 phosphorylation and activation [77]. In adipocytes, HIF1A also affects STAT3 activity through transcriptional activation of SOCS3, an inhibitor of STAT3 signaling [36]. In mesenchymal stem cells, SOX11 transcriptionally increases expression of BMP receptors, which leads to activation of SMAD1 [68].…”

Section: Cross-activation Through Downstream Effectorsmentioning

confidence: 99%

Selecting optimal combinations of transcription factors to promote axon regeneration: Why mechanisms matter

Venkatesh

Blackmore

2017

Neuroscience Letters

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Recovery from injuries to the central nervous system, including spinal cord injury, is constrained in part by the intrinsically low ability of many CNS neurons to mount an effective regenerative growth response. To improve outcomes, it is essential to understand and ultimately reverse these neuron-intrinsic constraints. Genetic manipulation of key transcription factors (TFs), which act to orchestrate production of multiple regeneration-associated genes, has emerged as a promising strategy. It is likely that no single TF will be sufficient to fully restore neuron-intrinsic growth potential, and that multiple, functionally interacting factors will be needed. An extensive literature, mostly from non-neural cell types, has identified potential mechanisms by which TFs can functionally synergize. Here we examine four potential mechanisms of TF/TF interaction; physical interaction, transcriptional cross-regulation, signaling-based cross regulation, and co-occupancy of regulatory DNA. For each mechanism, we consider how existing knowledge can be used to guide the discovery and effective use of TF combinations in the context of regenerative neuroscience. This mechanistic insight into TF interactions is needed to accelerate the design of effective TF-based interventions to relieve neuron-intrinsic constraints to regeneration and to foster recovery from CNS injury.

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Hypoxia-inducible Factor 1α Regulates a SOCS3-STAT3-Adiponectin Signal Transduction Pathway in Adipocytes

Cited by 62 publications

References 51 publications

Vascular reactivity and biomarkers of endothelial function in healthy subjects exposed to acute hypobaric hypoxia

Vascular reactivity and biomarkers of endothelial function in healthy subjects exposed to acute hypobaric hypoxia

Metabolism-Centric Overview of the Pathogenesis of Alzheimer's Disease

Selecting optimal combinations of transcription factors to promote axon regeneration: Why mechanisms matter

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