Circulating MiRNAs Are Associated With Low-grade Systemic Inflammation and Leptin Levels in Older Adults.

Inflammaging refers to the low-grade systemic inflammation that occurs with aging present in chronic non-communicable diseases. MicroRNAs (miRNAs) are potential biomarkers for these diseases in older adults. This study aimed to assess the expression of 21 circulating miRNAs and their associations with inflammatory biomarkers in older adults. This cross-sectional study was performed with 200 individuals participating in ISA-Nutrition. The systemic low-grade inflammation score (SIS) was calculated from the plasma concentration of 10 inflammatory biomarkers. Circulating miRNA expression was assessed using the Fluidigm method. Wilcoxon-Mann-Whitney test was employed to determine differences in SIS among groups distributed according to sex and presence of MetS. Spearman's correlation was used to estimate correlations among SIS, leptin levels, miRNA expression, and variables of interest. Analyses were performed using software R version 4.2.3, with a significance level of 0.05. The final sample consisted of 193 individuals with a mean age of 69.1 (SE = 0.5) years, being 64.7% individuals with metabolic syndrome (MetS). Positive correlations were observed between leptin concentration and metabolic risk factors, and leptin concentration was higher in individuals with MetS compared to those without MetS. The expression of 15 circulating miRNAs was negatively correlated with leptin concentration. GLMs showed negative associations between miRNAs (miR-15a, miR-16, miR-223, miR-363, miR-532), leptin, and/or SIS values; and only miR-21 showed positive association with SIS values. The results suggest the presence of peripheral leptin resistance associated with low-grade inflammation and plasma expression of miRNAs in older adults. These findings suggest the potential role of miRNAs as biomarkers for cardiometabolic risk.

Association between circulating micro-ribonucleic acids and metabolic syndrome in older adults from a population-based study.

BACKGROUND AND AIMS: Aging is a major factor in development of chronic non-communicable diseases (NCD). Epigenetic causes are risk factors in NCD development since studies indicate that the expression of micro-ribonucleic acids (miRs) is altered under different clinical conditions. This study aimed to analyze the expression profile of circulating miRs and investigate their association with biomarkers of cardiometabolic risk in older adults living in São Paulo municipality, Brazil. METHODS: A cross-sectional study was conducted based on the analysis of data from 200 older adults, with a mean age of 69.1 (0.5) years old participating in the ISA-Nutrition. The expression profiles of 21 plasma miRs related to glycemic and lipid metabolism, adiposity, and inflammation were evaluated in relation to cardiometabolic risk. Individuals were distributed into groups according to diagnosis of metabolic syndrome (MetS). The Stata Somersd module was used to calculate confidence intervals for Kendall's tau-a to estimate the correlations among variables. RESULTS: Differences in the plasma expression were observed in two of the 21 miRs evaluated according to the MetS presence in participants. Individuals with MetS showed higher expression of miR-30a and miR-122 than individuals without MetS. CONCLUSIONS: Considering that miR-30, and miR-122 were altered due to MetS, these miRs may be potential biomarkers for MetS in older adults.

Circulating microRNA Related to Cardiometabolic Risk Factors for Metabolic Syndrome: A Systematic Review.

MicroRNA regulates multiple pathways in inflammatory response, adipogenesis, and glucose and lipid metabolism, which are involved in metabolic syndrome (MetS). Thus, this systematic review aimed at synthesizing the evidence on the relationships between circulating microRNA and risk factors for MetS. The systematic review was registered in the PROSPERO database (CRD42020168100) and included 24 case-control studies evaluating microRNA expression in serum/plasma of individuals ≥5 years old. Most of the studies focused on 13 microRNAs with higher frequency and there were robust connections between miR-146a and miR-122 with risk factors for MetS, based on average weighted degree. In addition, there was an association of miR-222 with adiposity, lipid metabolism, glycemic metabolism, and chronic inflammation and an association of miR-126, miR-221, and miR-423 with adiposity, lipid, and glycemic metabolism. A major part of circulating microRNA was upregulated in individuals with risk factors for MetS, showing correlations with glycemic and lipid markers and body adiposity. Circulating microRNA showed distinct expression profiles according to the clinical condition of individuals, being particularly linked with increased body fat. However, the exploration of factors associated with variations in microRNA expression was limited by the variety of microRNAs investigated by risk factor in diverse studies identified in this systematic review.

Circulating microRNAs Showed Specific Responses according to Metabolic Syndrome Components and Sex of Adults from a Population-Based Study.

MicroRNAs (miRNAs) regulate several metabolic pathways and are potential biomarkers for early risk prediction of metabolic syndrome (MetS). Our aim was to evaluate the levels of 21 miRNAs in plasma according to MetS components and sex in adults. We employed a cross-sectional study of 192 adults aged 20 to 59 years old from the 2015 Health Survey of São Paulo with Focus in Nutrition. Data showed reduced levels of miR-16 and miR-363 in women with MetS; however, men with one or more risk factors showed higher levels of miR-let-7c and miR-30a. Individuals with raised waist circumference showed higher levels of miR-let-7c, miR-122, miR-30a, miR-146a, miR-15a, miR-30d and miR-222. Individuals with raised blood pressure had higher miR-30a, miR-122 and miR-30a levels. Plasma levels of four miRNAs (miR-16, miR-363, miR-375 and miR-486) were lower in individuals with low HDL-cholesterol concentrations. In addition, plasma levels of five miRNAs (miR-122, miR-139, miR-let-7c, miR-126 and miR-30a) were increased in individuals with high fasting plasma glucose and/or insulin resistance. Our results suggest that the pattern of miRNA levels in plasma may be a useful early biomarker of cardiometabolic components of MetS and highlight the sex differences in the plasma levels of miRNAs in individuals with MetS.

Fructose Consumption by Adult Rats Exposed to Dexamethasone In Utero Changes the Phenotype of Intestinal Epithelial Cells and Exacerbates Intestinal Gluconeogenesis.

Fructose consumption by rodents modulates both hepatic and intestinal lipid metabolism and gluconeogenesis. We have previously demonstrated that in utero exposure to dexamethasone (DEX) interacts with fructose consumption during adult life to exacerbate hepatic steatosis in rats. The aim of this study was to clarify if adult rats born to DEX-treated mothers would display differences in intestinal gluconeogenesis after excessive fructose intake. To address this issue, female Wistar rats were treated with DEX during pregnancy and control (CTL) mothers were kept untreated. Adult offspring born to CTL and DEX-treated mothers were assigned to receive either tap water (Control-Standard Chow (CTL-SC) and Dexamethasone-Standard Chow (DEX-SC)) or 10% fructose in the drinking water (CTL-fructose and DEX-fructose). Fructose consumption lasted for 80 days. All rats were subjected to a 40 h fasting before sample collection. We found that DEX-fructose rats have increased glucose and reduced lactate in the portal blood. Jejunum samples of DEX-fructose rats have enhanced phosphoenolpyruvate carboxykinase (PEPCK) expression and activity, higher facilitated glucose transporter member 2 (GLUT2) and facilitated glucose transporter member 5 (GLUT5) content, and increased villous height, crypt depth, and proliferating cell nuclear antigen (PCNA) staining. The current data reveal that rats born to DEX-treated mothers that consume fructose during adult life have increased intestinal gluconeogenesis while recapitulating metabolic and morphological features of the neonatal jejunum phenotype.

In Utero Dexamethasone Exposure Exacerbates Hepatic Steatosis in Rats That Consume Fructose During Adulthood.

Distinct environmental insults might interact with fructose consumption and contribute to the development of metabolic disorders. To address whether in utero glucocorticoid exposure and fructose intake modulate metabolic responses, adult female Wistar rats were exposed to dexamethasone (DEX) during pregnancy, and the offspring were administered fructose at a later time. Briefly, dams received DEX during the third period of pregnancy, while control dams remained untreated. Offspring born to control and DEX-treated mothers were defined as CTL-off and DEX-off, respectively, while untreated animals were designated CTL-off-CTL and DEX-off-CTL. CLT-off and DEX-off treated with 10% fructose in the drinking water for 8 weeks are referred to as CTL-off-FRU and DEX-off-FRU. We found that fructose promoted glucose intolerance and whole-body gluconeogenesis in both CTL-off-FRU and DEX-off-FRU animals. On the other hand, hepatic lipid accumulation was significantly stimulated in DEX-off-FRU rats when compared to the CTL-off-FRU group. The DEX-off-FRU group also displayed impaired very-low-density lipoprotein (VLDL) production and reduced hepatic expression of apoB, mttp, and sec22b. DEX-off-FRU has lower hepatic levels of autophagy markers. Taken together, our results support the unprecedented notion that in utero glucocorticoid exposure exacerbates hepatic steatosis caused by fructose consumption later in life.