Are epigenetic drugs for diabetes and obesity at our door step?

Arguelles, Andrix; Meruvu, Sunitha; Bowman, John D.; Choudhury, Mahua

doi:10.1016/j.drudis.2015.12.001

Cited by 64 publications

(34 citation statements)

References 91 publications

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“…Recent findings suggest a role for HDACs in cardiometabolic diseases and HDAC inhibitors have been tested in a variety of chronic diseases (Arguelles et al, 2015;Zhang & Ren, 2014). Valproic acid, classified as a nonspecific HDAC inhibitor, along with trichostatin A and butyric acid, are commonly used in the management of mood disorders and epilepsy to promote visceral obesity in humans by increasing newly formed adipocytes, similar to corticosteroids.…”

Section: Role Of Histone Modification In Obesogenesis and Cardiomyopathymentioning

confidence: 99%

Epigenetics and obesity cardiomyopathy: From pathophysiology to prevention and management

Zhang

Ren

2016

Pharmacology & Therapeutics

100

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Section: Role Of Histone Modification In Obesogenesis and Cardiomyopathymentioning

confidence: 99%

Epigenetics and obesity cardiomyopathy: From pathophysiology to prevention and management

Zhang

Ren

2016

Pharmacology & Therapeutics

100

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“…Indeed, a great variety of small molecules with epigenetic and anti-diabetic activity have been described in recent years. 78 These drugs, or potential new drugs, can be classified according to their epigenetic effects and have been generically named epigenetic drugs (or epidrugs). Presently, inhibitors of most of the enzymes responsible for epigenetic modifications are known and many of them are undergoing intense investigations.…”

Section: Potential Epigenetic Drugs and Related Clinical Trialsmentioning

confidence: 99%

Clinical relevance of epigenetics in the onset and management of type 2 diabetes mellitus

et al. 2017

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Epigenetics is involved in the altered expression of gene networks that underlie insulin resistance and insufficiency. Major genes controlling b-cell differentiation and function, such as PAX4, PDX1, and GLP1 receptor, are epigenetically controlled. Epigenetics can cause insulin resistance through immunomediated pro-inflammatory actions related to several factors, such as NF-kB, osteopontin, and Toll-like receptors. Hereafter, we provide a critical and comprehensive summary on this topic with a particular emphasis on translational and clinical aspects. We discuss the effect of epigenetics on b-cell regeneration for cell replacement therapy, the emerging bioinformatics approaches for analyzing the epigenetic contribution to type 2 diabetes mellitus (T2DM), the epigenetic core of the transgenerational inheritance hypothesis in T2DM, and the epigenetic clinical trials on T2DM. Therefore, prevention or reversion of the epigenetic changes occurring during T2DM development may reduce the individual and societal burden of the disease.

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“…To address this issue, our study showed HDAC3 as a potential, more specific target for WAT browning. Many studies have also concluded HDAC3 as an emerging target for inflammation, insulin-resistance, and type 2 diabetes [31,46,47,48,49,50] which are closely related to obesity. Future study might be directed to the capability of the HDAC3 inhibitor to induce browning of WAT, as our study highly suggested, especially in humans.…”

Section: Discussionmentioning

confidence: 99%

β-adrenergic Receptor Stimulation Revealed a Novel Regulatory Pathway via Suppressing Histone Deacetylase 3 to Induce Uncoupling Protein 1 Expression in Mice Beige Adipocyte

Yuliana

Jheng

Kawarasaki

et al. 2018

IJMS

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Browning of adipose tissue has been prescribed as a potential way to treat obesity, marked by the upregulation of uncoupling protein 1 (Ucp1). Several reports have suggested that histone deacetylase (HDAC) might regulate Ucp1 by remodelling chromatin structure, although the mechanism remains unclear. Herein, we investigate the effect of β-adrenergic receptor (β-AR) activation on the chromatin state of beige adipocyte. β-AR-stimulated Ucp1 expression via cold (in vivo) and isoproterenol (in vitro) resulted in acetylation of histone activation mark H3K27. H3K27 acetylation was also seen within Ucp1 promoter upon isoproterenol addition, favouring open chromatin for Ucp1 transcriptional activation. This result was found to be associated with the downregulation of class I HDAC mRNA, particularly Hdac3 and Hdac8. Further investigation showed that although HDAC8 activity decreased, Ucp1 expression was not altered when HDAC8 was activated or inhibited. In contrast, HDAC3 mRNA and protein levels were simultaneously downregulated upon isoproterenol addition, resulting in reduced recruitment of HDAC3 to the Ucp1 enhancer region, causing an increased H3K27 acetylation for Ucp1 upregulation. The importance of HDAC3 inhibition was confirmed through the enhanced Ucp1 expression when the cells were treated with HDAC3 inhibitor. This study highlights the novel mechanism of HDAC3-regulated Ucp1 expression during β-AR stimulation.

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Are epigenetic drugs for diabetes and obesity at our door step?

Cited by 64 publications

References 91 publications

Epigenetics and obesity cardiomyopathy: From pathophysiology to prevention and management

Epigenetics and obesity cardiomyopathy: From pathophysiology to prevention and management

Clinical relevance of epigenetics in the onset and management of type 2 diabetes mellitus

β-adrenergic Receptor Stimulation Revealed a Novel Regulatory Pathway via Suppressing Histone Deacetylase 3 to Induce Uncoupling Protein 1 Expression in Mice Beige Adipocyte

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