Non‑alcoholic fatty liver disease (NAFLD) is a widespread threat to human health. However, the present screening methods for NAFLD are time‑consuming or invasive. The present study aimed to assess the potential of microRNAs (miRNAs/miRs) in serum extracellular vesicles (EVs) as a biomarker of NAFLD. C57BL/6J mice were fed either a 12‑week high‑fat diet (HFD) or standard chow to establish NAFLD and control groups, respectively. Serum samples were obtained from the mouse model of NAFLD, as well as 50 patients with NAFLD and 50 healthy individuals, and EVs were extracted and verified. Using reverse transcription‑quantitative PCR, the mRNA expression level of selected miRNAs in the serum and EVs was analyzed. In order to determine the diagnostic value, receiver operating characteristic (ROC) curves were used. The mice treated with HFD showed notable hepatic steatosis and higher concentrations of serum alanine aminotransferase (ALT). There was also a significant decrease in the expression levels of miR‑135a‑3p, miR‑129b‑5p and miR‑504‑3p, and an increase in miR‑122‑5p expression levels in circulating EVs in mice treated with HFD and patients with NAFLD. There were also similar miR‑135a‑3p and miR‑122‑5p expression patterns in the serum. ROC analysis demonstrated that miR‑135a‑3p in circulating EVs was highly accurate in diagnosing NAFLD, with the area under the curve value being 0.849 (95% CI, 0.777‑0.921; P<0.0001). Bioinformatics analysis indicated that dysregulated miR‑135a‑3p was associated with ‘platelet‑derived growth factor receptor signaling pathway’ and ‘AMP‑activated protein kinase signaling pathway’. In summary, circulating miR‑135a‑3p in EVs may serve as a potential non‑invasive biomarker to diagnose NAFLD. This miRNA was a more sensitive and specific biological marker for NAFLD compared with ALT.

To investigate the molecular mechanisms underlying islet dysfunction and insulin resistance in diet-induced diabetes, we conducted temporal RNA sequencing of tissues responsible for insulin secretion (islets) and action (liver) every 4 weeks in mice on high-fat (HFD) or chow diet for 24 weeks, linking to longitudinal profile of metabolic characteristics. The diverse responses of α, β, and δ cells to glucose and palmitate indicated HFD-induced dynamic deterioration of islet function from dysregulation to failure. Insulin resistance developed with variable time course in different tissues. Weighted gene co-expression network analysis and Ingenuity Pathway Analysis implicated islets and liver jointly programmed β-cell compensatory adaption via cell proliferation at early phase and irreversible islet dysfunction by inappropriate immune response at later stage, and identified interconnected molecules including growth differentiation factor 15. Frequencies of T cell subpopulation showed an early decrement in Tregs followed by increases in Th1 and Th17 cells during progression to diabetes.

Although angina pectoris in patients with coronary heart disease often occurs when their forearms are in an elevated position for a prolonged period, and sympathetic activation is a major cause of this condition, little is known about the physiological effects of forearm elevation on sympathetic activity during forearm exercise. We hypothesized that forearm elevation augments sympathetic activation during the static handgrip exercise in humans. A total of 10 healthy male volunteers performed 2min of static handgrip exercise at 30% of maximal voluntary contraction followed by 2min of post-exercise muscle ischaemia (PEMI; specific activation of the muscle metaboreflex) with two forearm positions: the exercising forearm was elevated 50cm above the heart (forearm-elevated trial) or fixed at the level of the heart (heart-level trial). Muscle sympathetic nerve activity (MSNA), blood pressure and heart rate were monitored. MSNA increased during handgrip exercise in both forearm positions (P<0.001); the increase was 51% greater in the forearm-elevated trial (516±99 arbitrary units) than in the heart-level trial (346±44units; P<0.05). The increase in mean blood pressure was 8.4mmHg greater during exercise in the forearm-elevated trial (P<0.05), while changes in heart rate were similar in both forearm positions. The increase in MSNA during PEMI was 71% greater in the forearm-elevated trial (393±71 arbitrary units/min) than in the heart-level trial (229±29units/min; P<0.05). These results support the hypothesis that forearm elevation augments sympathetic activation during handgrip exercise. The excitatory effect of forearm elevation on exercising MSNA may be mediated primarily by increased activation of the muscle metaboreflex.

Aims: Growth differentiation factor-15 (GDF-15) and adiponectin are adipokines that regulate metabolism. This study aimed to evaluate the roles of GDF-15, adiponectin, and GDF-15/adiponectin ratio (G/A ratio) as biomarkers for detecting metabolic syndrome (MS).Materials and methods: This cross-sectional study included 676 participants aged 20–70 years in Jurong, China. The participants were divided into four groups based on sex and age (<40 and ≥40 years). MS was defined according to the modified National Cholesterol Education Program Adult Treatment Panel III criteria. Receiver operating characteristic curves were used to evaluate the performance of GDF-15, adiponectin, and the G/A ratio in predicting MS.Results: The prevalence of MS was 22.0% (149/676). Logistic regression analysis indicated that the G/A ratio and adiponectin levels, but not GDF-15 levels, were correlated with MS [odds ratio; 95% CI 1.010 (1.006–1.013) and 0.798 (0.735–0.865), respectively] after adjusting for confounding factors. The G/A ratio displayed a significant relationship with MS in each subgroup and with each MS component in both men and women; however, adiponectin concentrations were significantly associated with MS and all its components only in men (all P &lt;0.05). The area under the curve (AUC) of the G/A ratio and the adiponectin level for MS was 0.758 and 0.748, respectively. The highest AUC was 0.757 for the adiponectin level in men and 0.724 for the G/A ratio in women.Conclusions: This study suggests that the G/A ratio and adiponectin are potential biomarkers for detecting MS in women and men, respectively.