Augmentation of histone deacetylase 3 (HDAC3) epigenetic signature at the interface of proinflammation and insulin resistance in patients with type 2 diabetes

Chandrakumar, Sathishkumar; Prabu, Paramasivam; Balakumar, Mahalingam; Lenin, Raji Rajesh; Prabhu, Durai; Anjana, R M; Mohan, Viswanathan; Balasubramanyam, Muthuswamy

doi:10.1186/s13148-016-0293-3

Cited by 77 publications

(49 citation statements)

References 54 publications

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“…In a recent study, peripheral blood mononuclear cells were used to measure histone deacetylases (HDACs) activity and expression in relation to glycemia, inflammation and insulin resistance in patients with type 2 DM. Low-grade chronic inflammation and insulin resistance induced HDAC3 activity and expression, and correlated positively with circulating levels of TNF-α, IL-6, and other proinflammatory markers, and negatively with Sirt1 expression ( 114 ).…”

Section: Epigenetic Changesmentioning

confidence: 99%

Type 2 Diabetes Mellitus and Cardiovascular Disease: Genetic and Epigenetic Links

et al. 2018

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Type 2 diabetes mellitus (DM) is a common metabolic disorder predisposing to diabetic cardiomyopathy and atherosclerotic cardiovascular disease (CVD), which could lead to heart failure through a variety of mechanisms, including myocardial infarction and chronic pressure overload. Pathogenetic mechanisms, mainly linked to hyperglycemia and chronic sustained hyperinsulinemia, include changes in metabolic profiles, intracellular signaling pathways, energy production, redox status, increased susceptibility to ischemia, and extracellular matrix remodeling. The close relationship between type 2 DM and CVD has led to the common soil hypothesis, postulating that both conditions share common genetic and environmental factors influencing this association. However, although the common risk factors of both CVD and type 2 DM, such as obesity, insulin resistance, dyslipidemia, inflammation, and thrombophilia, can be identified in the majority of affected patients, less is known about how these factors influence both conditions, so that efforts are still needed for a more comprehensive understanding of this relationship. The genetic, epigenetic, and environmental backgrounds of both type 2 DM and CVD have been more recently studied and updated. However, the underlying pathogenetic mechanisms have seldom been investigated within the broader shared background, but rather studied in the specific context of type 2 DM or CVD, separately. As the precise pathophysiological links between type 2 DM and CVD are not entirely understood and many aspects still require elucidation, an integrated description of the genetic, epigenetic, and environmental influences involved in the concomitant development of both diseases is of paramount importance to shed new light on the interlinks between type 2 DM and CVD. This review addresses the current knowledge of overlapping genetic and epigenetic aspects in type 2 DM and CVD, including microRNAs and long non-coding RNAs, whose abnormal regulation has been implicated in both disease conditions, either etiologically or as cause for their progression. Understanding the links between these disorders may help to drive future research toward an integrated pathophysiological approach and to provide future directions in the field.

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Section: Epigenetic Changesmentioning

confidence: 99%

Type 2 Diabetes Mellitus and Cardiovascular Disease: Genetic and Epigenetic Links

et al. 2018

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“…More specifically related to T2D, a recent study using peripheral blood mononuclear cells showed that HDAC3 activity and HDAC3 mRNA levels were positively correlated with IR [ 66 ]. Although the direct effect of other diabetes medications on the epigenome is not known, a recent intriguing publication by Zhong et al revealed that the biguanide T2D drug metformin might affect DNA methylation.…”

Section: Epigenetics Microbiota and T2dmmentioning

confidence: 99%

Epigenetic Markers and Microbiota/Metabolite-Induced Epigenetic Modifications in the Pathogenesis of Obesity, Metabolic Syndrome, Type 2 Diabetes, and Non-alcoholic Fatty Liver Disease

et al. 2019

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Purpose of Review The metabolic syndrome is a pathological state in which one of the key components is insulin resistance. A wide spectrum of body compartments is involved in its pathophysiology. Genetic and environmental factors such as diet and physical activity are both related to its etiology. Reversible modulation of gene expression without altering the DNA sequence, known as epigenetic modifications, has been shown to drive this complex metabolic cluster of conditions. Here, we aim to examine some of the recent research of specific epigenetically mediated mechanisms and microbiota-induced epigenetic modifications on the development of adipose tissue and obesity, β-cell dysfunction and diabetes, and hepatocytes and non-alcoholic fatty disease. Recent Findings DNA methylation patterns and histone modifications have been identified in this context; the integrated analysis of genome, epigenome, and transcriptome is likely to expand our knowledge of epigenetics in health and disease. Epigenetic modifications induced by diet-related microbiota or metabolites possibly contribute to the insulin-resistant state. Summary The identification of epigenetic signatures on diabetes and obesity may give us the possibility of developing new interventions, prevention measures, and follow-up strategies.

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“…Augmentation of HDAC3 leads to diabetes, and the present study showed its association with DFU [ 42 ]. Park et al reported that knockdown of HDAC3 induces angiogenic VEGF and plasminogen activator inhibitor-1 [ 43 ].…”

Section: Discussionmentioning

confidence: 77%

Gene Expression Profiling of Multiple Histone Deacetylases (HDAC) and Its Correlation with NRF2-Mediated Redox Regulation in the Pathogenesis of Diabetic Foot Ulcers

et al. 2020

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Nuclear factor erythroid-2-related factor 2 (Nrf2) is a protein of the leucine zipper family, which mitigates inflammation and employs cytoprotective effects. Attempting to unravel the epigenetic regulation of type 2 diabetes mellitus (T2DM) and diabetic foot ulcer (DFU), we profiled the expression of eleven isoform-specific histone deacetylases (HDACs) and correlated them with NRF2 and cytokines. This study recruited a total of 60 subjects and categorized into DFU patients (n = 20), T2DM patients (n = 20), and healthy controls (n = 20). The DFU patients were subcategorized into uninfected and infected DFU (n = 10 each). We observed a progressive decline in the expression of NRF2 and its downstream targets among T2DM and DFU subjects. The inflammatory markers IL-6 and TNF-α were significantly upregulated, whereas anti-inflammatory marker IL-10 was significantly downregulated in DFU. Of note, a significant upregulation of HDAC1, 3, 4, 11, SIRT3 and downregulation of HDAC2,8, SIRT1, SIRT2, SIRT3, SIRT7 among DFU patients were observed. The significant positive correlation between NRF2 and SIRT1 in DFU patients suggested the vital role of NRF2/SIRT1 in redox homeostasis and angiogenesis. In contrast, the significant negative correlation between NRF2 and HDAC1, 3 and 4, implied an imbalance in NRF2-HDAC1, 3, 4 circuit. Furthermore, a significant positive correlation was observed between HDAC4 and IL-6, and the negative correlation between SIRT1 and IL-6 suggested the pro-inflammatory role of HDAC4 and the anti-inflammatory role of SIRT1 in NRF2 signaling. In conclusion, the epigenetic changes such as upregulation of HDAC1, 3, 4, 11, SIRT3 and downregulation of HDAC2, 8, SIRT1, SIRT2, SIRT6, SIRT7 and their association with NRF2 as well as inflammatory markers are suggestive of their roles in pathophysiology of T2DM and DFU.

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Augmentation of histone deacetylase 3 (HDAC3) epigenetic signature at the interface of proinflammation and insulin resistance in patients with type 2 diabetes

Cited by 77 publications

References 54 publications

Type 2 Diabetes Mellitus and Cardiovascular Disease: Genetic and Epigenetic Links

Type 2 Diabetes Mellitus and Cardiovascular Disease: Genetic and Epigenetic Links

Epigenetic Markers and Microbiota/Metabolite-Induced Epigenetic Modifications in the Pathogenesis of Obesity, Metabolic Syndrome, Type 2 Diabetes, and Non-alcoholic Fatty Liver Disease

Gene Expression Profiling of Multiple Histone Deacetylases (HDAC) and Its Correlation with NRF2-Mediated Redox Regulation in the Pathogenesis of Diabetic Foot Ulcers

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