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Background and Aims: Overweight and obesity are important risk factors for chronic disorders. Fat accumulation is one of the central manifestations; it occurs via a complex mechanism where multiple metabolic signals converge. Sirtuins are an enzyme family with deacetylase functions that are implicated in the regulation of several genes. Sirt1 and its upstream regulator (miR-34a) are elements of a converging mechanism that integrates the dynamic metabolic state. In this work, we hypothesized that elevated levels of miR-34a in overweight/obese group inhibits Sirt1 activity. Therefore, we studied the miR-34a/Sirt1 axis in mononuclear cells obtained from adipose tissue., Methods: Adipose tissue samples were collected from 36 subjects, and they were categorized according to body mass index (BMI) as overweight/obesity and normoweight. Subcutaneous adipose tissue samples were enzymatically dissociated, and mononuclear cells from adipose tissue were isolated by Ficoll Hypaque. Sirt1-positive cells and relative Sirt1 expression were determined by flow cytometry and real-time polymerase chain reaction (qPCR), respectively. Finally, Sirt1 activity was measured with a luminescence assay., Results: The percentage of Sirt1-positive mononuclear cells from adipose tissue decreased along with Sirt1 enzymatic activity in overweight/obese participants. miR-34a expression increased in the overweight/obese group compared to normoweight individuals. There was a negative association between the relative miR-34a expression and Sirt1-positive cells and a synergistic effect on Sirt1-positive cells mediated by the miR-34a inhibitor and Sirt1 agonist., Conclusions: Our results describe for the first time the presence of miR-34a and Sirt1 in mononuclear cells isolated from subcutaneous adipose tissue. Additionally, these results suggest altered sirtuin function in overweight/obese patients and open the possibility for new therapies that involve these metabolic targets., Competing Interests: Declaration of competing interest The authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (Copyright © 2020 Diabetes India. Published by Elsevier Ltd. All rights reserved.)

miRNAs are important immune regulators in the control of the CD4 + T cells phenotype. miR-326 regulates the differentiation towards Th17 cells and the inhibition of miR-155 is associated with low levels of Treg cells. However, miRNAs expression and transcription factors associated with these lymphocyte subsets in obesity-induced adipose tissue inflammation is still unknown. The aim of this work was to identify Th17 cells in subcutaneous adipose tissue (SAT), proinflammatory cytokine production and their association with the miRNAs and transcription factors involved. We collected SAT samples obtained by lipoaspiration from individuals with normal weight, overweight and obesity. We obtained the stromal vascular fractions and then a Ficoll gradient was performed to obtain adipose tissue mononuclear cells (ATMC). Th17 cells were evaluated by flow cytometry and the expression of miR-326, miR-155, RORC2 and FOXP3 by qRT-PCR. We also analyzed cytokines from the supernatants of the ATMC culture and measured the FOXP3 methylation percentage by bisulfite conversion by PCR. According to the results, the frequency of Th17 cells and RORC2 expression was higher in individuals with obesity and associated with miR-326 expression. The ATMC from this group secreted a proinflammatory cytokine profile by in vitro assay. In contrast, lower levels of mRNA FOXP3 expression was detected in ATMC from individuals with obesity that correlated with methylation percentage of FOXP3 gene but no association with miR-155 was detected. Our results suggested that miR-326 participates in the polarization towards Th17 promoting the inflammatory state in the obesity-induced adipose tissue., (Copyright © 2019 European Federation of Immunological Societies. Published by Elsevier B.V. All rights reserved.)

Introduction: Sirtuins regulate energy metabolism and insulin sensitivity through their ability to act as energy sensors and regulators in several metabolic tissues., Aim: To evaluate the expression levels of sirtuin genes SIRT1, SIRT2, SIRT3 and SIRT6 and their target genes (PPAR-α, PGC1-α, NRF1, DGAT1, PPAR-γ and FOXO3a) in subcutaneous adipose tissue collected from individuals with normoweight, overweight and obesity., Methods: Adipose tissue samples, obtained by lipoaspiration during liposuction surgery, were processed to obtain RNA, which was reverse-transcribed to cDNA. Then, we measured the expression levels of each gene by qPCR., Results: We found differences in the mRNA expression of SIRT1, SIRT2, SIRT3 and SIRT6 and their target genes (PPAR-α, PGC1-α, NRF1, DGAT1, PPAR-γ and FOXO3a) in adipose tissue from overweight or obese subjects when compared to normoweight subjects. All genes analyzed, except SIRT2, showed correlation with BMI., Conclusions: Our findings in human subcutaneous adipose tissue show that increased body mass index modifies the expression of genes encoding sirtuins and their target genes, which are metabolic regulators of adipose tissue. Therefore, these could be used as biomarkers to predict the ability of adipose tissue to gain mass of adipose tissue., (Copyright © 2018 Diabetes India. Published by Elsevier Ltd. All rights reserved.)

Scope: The scope of this review is to explain how metabolic disorders originated by a deficient nutrition can develop into a neoplastic process by the alteration of epigenetic mechanisms like miRNAs. Obesity is a proinflammatory state with a wide impact on health around the world that is associated with neoplastic diseases. Epigenetic mechanisms have a central role in the obesogenic environment, which participates on the development of comorbidities such as cancer., Methods and Results: We made an exhaustive review of the most recent reports about metabolic disorders with nutrition and their relationship with miRNAs, and their risk of developing into oncogenic processes. MicroRNAs (miRNAs) act as one of the major epigenetic mechanisms that can affect the metabolic reprogramming of cellular metabolism that plays an important role in the oncogenic process. There is evidence that some foods may contribute to diminishing the risk of cancer as well as epidemiological studies that support the notion that diets high in animal protein and fat promote cancer risk. Therefore, diets high in fruit and vegetables reduce the risk of cancer. One of the principal explanations is that these foods contain bioactive compounds that increase the efficacy of epigenetic mechanisms, which in turn decrease the risk of obesity and its comorbidities., Conclusion: In this review, we show how miRNAs are implicated in several signaling pathways as well as illustrating some bioactive compounds that impact inflammation and cancer development., (© 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

The pathogenesis of type 2 diabetes (T2D) is associated with a progressive loss of pancreatic β‐cell mass. It is known that miR‐146a, miR‐34a, and miR‐375 are involved in β‐cell functionality. In this work, we evaluated the levels of these miRNAs in normal‐glycaemic individuals, pre‐diabetic, and T2D patients in relation to β‐cell functionality, insulin resistance, and metabolic parameters. The relative expression of the miRNAs was evaluated in serum samples by real‐time polymerase chain reaction. In a principal component analysis, we observed that T2D patients and pre‐diabetic individuals were not associated with β‐cell functionality. However, in a correlation matrix analysis, we detected that miR‐34a was related to miR‐146a and insulin resistance. The relative expression of miR‐375 was correlated with cholesterol and low‐density lipoprotein levels. A decrease of β‐cell function in pre‐diabetic individuals and T2D patients was observed. The insulin resistance was higher in pre‐diabetic individuals and T2D patients. The relative expression of miR‐146a in pre‐diabetic individuals, T2D patients with insulin treatment, and T2D patients with nephropathy and diabetic foot was decreased. In addition, miR‐34a was increased in T2D patients who were overweight and obese. The relative expression of miR‐375 was increased in T2D patients with poor glycaemic control, while a decrease was seen in T2D patients with nephropathy and diabetic foot. Circulating miR‐375, miR‐34a, and miR‐146a were not associated with β‐cell functionality, but their expression was differentially affected by glycaemia, obesity, insulin treatment, and the presence of nephropathy and diabetic foot. [ABSTRACT FROM AUTHOR]

Breast cancer (BRCA) is the most frequent cancer type that afflicts women. Unfortunately, despite all the current therapeutic strategies, many patients develop chemoresistance hampering the efficacy of treatment. Hence, an early indicator of therapy efficacy might aid in the search for better treatment and patient survival. Although emerging evidence indicates a key role of the purinergic receptors P2X7 and A2A in cancer, less is known about their involvement in BRCA chemoresistance. In this sense, as the chemotherapeutic treatment stimulates immune system response, we evaluated the expression and function of P2X7 and A2A receptors in CD8+ T cells before and four months after BRCA patients received neoadjuvant chemotherapy. The results showed an increase in the levels of expression of P2X7 and a decrease in the expression of A2A in CD8+ T cells in non-chemoresistant (N-CHR) patients, compared to chemoresistant (CHR) patients. Interestingly, in CHR patients, reduced expression of P2X7 occurs along with a decrease in the CD62L shedding and the production of IFN-γ. In the case of the A2A function, the inhibition of IFN-γ production was not observed after chemotherapy in CHR patients. A possible relationship between the modulation of the expression and function of the P2X7 and A2A receptors was found, according to the molecular subtypes, where the patients that were triple-negative and human epidermal growth factor receptor 2 (HER2)-enriched presented more alterations. Comorbidities such as overweight/obesity and type 2 diabetes mellitus (T2DM) participate in the abnormalities detected. Our results demonstrate the importance of purinergic signaling in CD8+ T cells during chemoresistance, and it could be considered to implement personalized therapeutic strategies. [ABSTRACT FROM AUTHOR]

Introduction: Background: prediabetes is a state observed before type-2 diabetes. Nowadays the obesity epidemic could be due to a rise in the incidence of prediabetes. Mexico has public policies for the management of non-communicable diseases. However, obesity rates continue to increase. The aim of this study was to elaborate on a diagnosis of prediabetes in the pediatric Mexican population, and compare the proportions of comorbidities that children with and without prediabetes had. Methods: a cross-sectional study was performed with 569 participants of 4 to 19 years of age from public schools. Anthropometric (weight, height, and waist circumference), clinical (blood pressure), and biochemical (fasting glucose, lipidic profile, and uric acid) variables were collected. Results: in all, 8.6 % of the population had prediabetes. Variables with the highest altered prevalence included triglycerides and systolic blood pressure. Boys had higher rates of prediabetes, altered BP, and hyperuricemia than girls. Children with prediabetes had a greater risk of elevated waist circumference, blood pressure, and uric acid measures. Conclusions: the Mexican pediatric population had elevated rates of prediabetes. Furthermore, the group with prediabetes had a higher risk of presenting high values of triglycerides, blood pressure, uric acid, and total cholesterol. [ABSTRACT FROM AUTHOR]

Th17 cells are involved in the pathogenesis of multiple inflammatory diseases such as type two diabetes (T2D). CD39 + Treg cells have been implicated as responsible for suppressing Th17 cells. The aim of this study was to evaluate the number and function of CD4 + CD25 high CD39 + Treg and Th17 cells in peripheral blood mononuclear cells (PBMC) from T2D patients and healthy control subjects. The Th17 cells were detected in PBMC under culture with human anti-CD3/CD28 and PMA/ionomycin and the levels of IL-17 were assessed by ELISA and qPCR. The T2D patients with obesity showed significantly lower percentages of CD39 + Treg cells. A negative correlation between CD39 + Treg cells and weight, and body mass index was detected. In contrast, the low levels of CD4 + IL-17 + cells in overweight and obese T2D patients showed a positive correlation with glucose and HbA1c. Additionally, we found a subpopulation of Th17 cells that express CD39 and were correlated with glucose and HbA1c. Our findings suggest that the expression of CD39 on Treg cells and also in CD4 + IL-17 + cells from T2D patients is related to hyperglycemia as well as to overweight and obesity and therefore may participate as a modulator of the effector capacity of Th17 cells. [ABSTRACT FROM AUTHOR]