DNA methylation in cardiovascular disease and heart failure: novel prediction models?

Background: Cardiovascular diseases (CVD) affect over half a billion people worldwide and are the leading cause of global deaths. In particular, due to population aging and worldwide spreading of risk factors, the prevalence of heart failure (HF) is also increasing. HF accounts for approximately 36% of all CVD-related deaths and stands as the foremost cause of hospitalization.

Altered H3K4me3 profile at the TFAM promoter causes mitochondrial alterations in preadipocytes from first-degree relatives of type 2 diabetics.

Background: First-degree relatives of type 2 diabetics (FDR) exhibit a high risk of developing type 2 diabetes (T2D) and feature subcutaneous adipocyte hypertrophy, independent of obesity. In FDR, adipose cell abnormalities contribute to early insulin-resistance and are determined by adipocyte precursor cells (APCs) early senescence and impaired recruitment into the adipogenic pathway. Epigenetic mechanisms signal adipocyte differentiation, leading us to hypothesize that abnormal epigenetic modifications cause adipocyte dysfunction and enhance T2D risk.

The Transcription Factor : Novel Insights into Metabolic Diseases and Adipose Tissue Dysfunction.

The transcription factor , from the gene family, has long been studied due to its critical role in physiological activities in normal cells, such as organ development and body patterning, and pathological activities in cancer cells. Nonetheless, recent evidence supports the hypothesis of a role for in metabolic diseases, particularly in obesity and type 2 diabetes (T2D). In line with the current opinion that adipocyte and adipose tissue (AT) dysfunction belong to the group of primary defects in obesity, linking this condition to an increased risk of insulin resistance (IR) and T2D, the gene has been shown to regulate adipocyte function and AT remodeling both in humans and mice.

Methylglyoxal Impairs the Pro-Angiogenic Ability of Mouse Adipose-Derived Stem Cells (mADSCs) via a Senescence-Associated Mechanism.

Adipose-derived stem cells (ADSCs) play a crucial role in angiogenesis and repair of damaged tissues. However, in pathological conditions including diabetes, ADSC function is compromised. This work aims at evaluating the effect of Methylglyoxal (MGO), a product of chronic hyperglycemia, on mouse ADSCs' (mADSCs) pro-angiogenic function and the molecular mediators involved.

Epigenetic Reprogramming of the Inflammatory Response in Obesity and Type 2 Diabetes.

For the past several decades, the prevalence of obesity and type 2 diabetes (T2D) has continued to rise on a global level. The risk contributing to this pandemic implicates both genetic and environmental factors, which are functionally integrated by epigenetic mechanisms. While these conditions are accompanied by major abnormalities in fuel metabolism, evidence indicates that altered immune cell functions also play an important role in shaping of obesity and T2D phenotypes.

Epigenetic Dysregulation of the () Gene Associates with Subcutaneous Adipocyte Hypertrophy in Human Obesity.

Along with insulin resistance and increased risk of type 2 diabetes (T2D), lean first-degree relatives of T2D subjects (FDR) feature impaired adipogenesis in subcutaneous adipose tissue (SAT) and subcutaneous adipocyte hypertrophy well before diabetes onset. The molecular mechanisms linking these events have only partially been clarified. In the present report, we show that silencing of the transcription factor () in human preadipocytes impaired differentiation in mature adipose cells in vitro.

ZMAT3 hypomethylation contributes to early senescence of preadipocytes from healthy first-degree relatives of type 2 diabetics.

Senescence of adipose precursor cells (APC) impairs adipogenesis, contributes to the age-related subcutaneous adipose tissue (SAT) dysfunction, and increases risk of type 2 diabetes (T2D). First-degree relatives of T2D individuals (FDR) feature restricted adipogenesis, reflecting the detrimental effects of APC senescence earlier in life and rendering FDR more vulnerable to T2D. Epigenetics may contribute to these abnormalities but the underlying mechanisms remain unclear.

DNA Methylation and Type 2 Diabetes: Novel Biomarkers for Risk Assessment?

Diabetes is a severe threat to global health. Almost 500 million people live with diabetes worldwide. Most of them have type 2 diabetes (T2D).

Surgical stress and metabolic response after totally laparoscopic right colectomy.

No clear consensus on the need to perform an intracorporeal anastomosis (IA) after laparoscopic right colectomy is currently available. One of the potential benefits of intracorporeal anastomosis may be a reduction in surgical stress. Herein, we evaluated the surgical stress response and the metabolic response in patients who underwent right colonic resection for colon cancer.

Adipocyte precursor cells from first degree relatives of type 2 diabetic patients feature changes in hsa-mir-23a-5p, -193a-5p, and -193b-5p and insulin-like growth factor 2 expression.

First-degree relatives (FDRs) of type 2 diabetics (T2D) feature dysfunction of subcutaneous adipose tissue (SAT) long before T2D onset. miRNAs have a role in adipocyte precursor cells (APC) differentiation and in adipocyte identity. Thus, impaired miRNA expression may contribute to SAT dysfunction in FDRs.

The Pervasive Effects of ER Stress on a Typical Endocrine Cell: Dedifferentiation, Mesenchymal Shift and Antioxidant Response in the Thyrocyte.

The endoplasmic reticulum stress and the unfolded protein response are triggered following an imbalance between protein load and protein folding. Until recently, two possible outcomes of the unfolded protein response have been considered: life or death. We sought to substantiate a third alternative, dedifferentiation, mesenchymal shift, and activation of the antioxidant response by using typical endocrine cells, i.

Altered DNA methylation associates with restricted adipogenesis in healthy first-degree relatives of Type 2 diabetes subjects.

First-degree relatives (FDR) of individuals with Type 2 diabetes (T2D) feature restricted adipogenesis, which render them more vulnerable to T2D. Epigenetics may contribute to these abnormalities. FDR pre-adipocyte and Transcriptome were investigated by MeDIP- and RNA-Seq, respectively.

L. Dry Extracts Ameliorate Adipocyte Differentiation of 3T3-L1 Cells Exposed to TNFα by Down-Regulating Expression.

L. dry extracts (de) improve adipogenesis in vitro. These effects are dependent from an early modulation of CCAAT/enhancer-binding protein beta () expression and cyclic Adenosine Monophosphate (cAMP) response element-binding protein () activation.

Chronic Adipose Tissue Inflammation Linking Obesity to Insulin Resistance and Type 2 Diabetes.

Obesity is one of the major health burdens of the 21st century as it contributes to the growing prevalence of its related comorbidities, including insulin resistance and type 2 diabetes. Growing evidence suggests a critical role for overnutrition in the development of low-grade inflammation. Specifically, chronic inflammation in adipose tissue is considered a crucial risk factor for the development of insulin resistance and type 2 diabetes in obese individuals.

Epigenetic silencing of the ANKRD26 gene correlates to the pro-inflammatory profile and increased cardio-metabolic risk factors in human obesity.

Background: Obesity is a major worldwide threat to human health. Increasing evidence indicates that epigenetic modifications have a major impact on the natural history of this disorder. Ankyrin Repeat Domain 26 (Ankrd26) is involved in the development of both obesity and diabetes in mice and is modulated by environmentally induced epigenetic modifications.

KCTD1: A novel modulator of adipogenesis through the interaction with the transcription factor AP2α.

Adipogenesis has an important role in regulating energy balance, tissue homeostasis and disease pathogenesis. 3T3-L1 preadipocytes have been widely used as an in vitro model for studying adipocyte differentiation. We here show that KCTD1, a member of the potassium channel containing tetramerization domain proteins, plays an active role in adipogenesis.

Nutritional Factors, DNA Methylation, and Risk of Type 2 Diabetes and Obesity: Perspectives and Challenges.

A healthy diet improves life expectancy and helps to prevent common chronic diseases such as type 2 diabetes (T2D) and obesity. The mechanisms driving these effects are not fully understood, but are likely to involve epigenetics. Epigenetic mechanisms control gene expression, maintaining the DNA sequence, and therefore the full genomic information inherited from our parents, unchanged.

Adipose Tissue Dysfunction as Determinant of Obesity-Associated Metabolic Complications.

Obesity is a critical risk factor for the development of type 2 diabetes (T2D), and its prevalence is rising worldwide. White adipose tissue (WAT) has a crucial role in regulating systemic energy homeostasis. Adipose tissue expands by a combination of an increase in adipocyte size (hypertrophy) and number (hyperplasia).

High-fat diet unveils an enhancer element at the Ped/Pea-15 gene responsible for epigenetic memory in skeletal muscle.

Background: The impact of nutrition on the evolution towards type 2 diabetes has recently received increasing attention because of the effect on chromatin structure and gene expression.

Purpose: Evaluate the effect of high-fat diet on chromatin remodelling and expression of Ped/Pea-15, a gene commonly overexpressed in individuals at risk of type 2 diabetes.

Methods: We used mouse and cell models to investigate Ped/Pea-15 transcriptional regulation by high-fat diet and glucose, respectively.

Citrus aurantium L. dry extracts promote C/ebpβ expression and improve adipocyte differentiation in 3T3-L1 cells.

Metabolic and/or endocrine dysfunction of the white adipose tissue (WAT) contribute to the development of metabolic disorders, such as Type 2 Diabetes (T2D). Therefore, the identification of products able to improve adipose tissue function represents a valuable strategy for the prevention and/or treatment of T2D. In the current study, we investigated the potential effects of dry extracts obtained from Citrus aurantium L.

The Destiny of Glucose from a MicroRNA Perspective.

Glucose serves as a primary, and for some tissues the unique, fuel source in order to generate and maintain the biological functions. Hyperglycemia is a hallmark of type 2 diabetes and is the direct consequence of perturbations in the glucose homeostasis. Insulin resistance, referred to as a reduced response of target tissues to the hormone, contributes to the development of hyperglycemia.

Prep1 deficiency improves metabolic response in white adipose tissue.

Prep1 is a gene encoding for a homeodomain transcription factor which induces hepatic and muscular insulin resistance. In this study, we show that Prep1 hypomorphic heterozygous (Prep1) mice, expressing low levels of protein, featured a 23% and a 25% reduction of total body lipid content and epididymal fat, respectively. The percentage of the small adipocytes (25-75 μm) was 30% higher in Prep1 animals than in the WT, with a reciprocal difference in the large adipose cells (100-150 and >150 μm).

Epigenetic modifications of the Zfp/ZNF423 gene control murine adipogenic commitment and are dysregulated in human hypertrophic obesity.

Aims/hypothesis: Subcutaneous adipocyte hypertrophy is associated with insulin resistance and increased risk of type 2 diabetes, and predicts its future development independent of obesity. In humans, subcutaneous adipose tissue hypertrophy is a consequence of impaired adipocyte precursor cell recruitment into the adipogenic pathway rather than a lack of precursor cells. The zinc finger transcription factor known as zinc finger protein (ZFP) 423 has been identified as a major determinant of pre-adipocyte commitment and maintained white adipose cell function.

Targetting PED/PEA-15 for diabetes treatment.

PED/PEA-15 is an ubiquitously expressed protein, involved in the regulation of proliferation and apoptosis. It is commonly overexpressed in Type 2 Diabetes (T2D) and in different T2D-associated comorbidities, including cancer and certain neurodegenerative disorders. Areas covered: In mice, Ped/Pea-15 overexpression impairs glucose tolerance and, in combination with high fat diets, further promotes insulin resistance and T2D.