Circulating Irisin and Myostatin as Markers of Muscle Strength and Physical Condition in Elderly Subjects.

BACKGROUND AND OBJECTIVE: Aging is a physiological process known to produce changes in body composition, affecting the musculature and leading to decreased muscle strength. Muscle in response to exercise acts as an endocrine organ, producing and releasing myokines such as irisin and myostatin that modulate muscular growth. Here, we aimed to evaluate the effects of low intensity resistance exercise, with or without protein supplementation, on body composition, anthropometric parameters and circulating irisin and myostatin in elderly subjects. METHODS: This is a prospective and controlled clinical trial in which subjects were randomized into 3 groups: (1) control group (n = 20), (2) low intensity resistance exercise group (RE) (n = 14), and (3) low intensity resistance exercise and nutritional support group (RENS) (n = 9). Participants, aged 60-75 years, were studied at baseline and 16 weeks thereafter. Body composition was evaluated through bioelectric impedance. Serum irisin and myostatin was measured using ELISA. RESULTS: At follow-up, RENS resulted in a significant increase in fat free mass (47.4 ± 7.4 vs. 46.5 ± 7.4, p = 0.046), the calf muscle circumference (36.4 ± 1.3 vs. 32.3 ± 4.3, p = 0.025), and circulating irisin (3 ± 1.1 vs. 2.6 ± 1.3, p = 0.030) compared to baseline. RE resulted in a significant increase in grip strength (17.2 ± 4.6 vs. 15.3 ± 4.6, p = 0.011) and irisin (3.1 ± 0.8 vs. 2.4 ± 0.3, p = 0.011) and decreased walking speed at different distance (p < 0.02). Opposite findings in these parameters were observed in control intervention. In line with these findings, the percent change of calf muscle circumference (p = 0.003) and fat free mass (p < 0.0001) were significantly increased in RENS compared to control, whereas fat mass (p = 0.033) was decreased. Interestingly, in this group, strength was positively correlated with fat free mass (r = 0.782, p = 0.008), and circulating irisin was significantly decreased in those participants with strength loss at the end of the study (p = 0.002). No significant correlation between circulating irisin and myostatin in any group was observed. CONCLUSION: Circulating irisin, but not myostatin, constitutes a marker for improved muscular performance in elderly subjects.

Surgery-Induced Weight Loss Is Associated With the Downregulation of Genes Targeted by MicroRNAs in Adipose Tissue.

CONTEXT: Molecular mechanisms associated with physiological variations in adipose tissue (AT) are not fully recognized. The most recent reports highlight the critical relevance of microRNAs (miRNAs) found in AT. OBJECTIVE: To identify changes in messenger RNA (mRNA) and miRNA expressions and their interaction in human AT before and after surgery-induced weight loss. Research Design and Setting: Genome-wide mRNA and miRNA expressions were assessed by microarrays in abdominal subcutaneous AT of 16 morbidly obese women before and 2 years after laparoscopic Roux-en-Y gastric bypass. The association of changes in miRNAs with their respective mRNA targets was studied. The results were replicated in publicly available microarray datasets. Validation was made by real-time polymerase chain reaction in additional fat samples from 26 age-matched lean women and in isolated human adipocytes. RESULTS: A total of 5018 different mRNA probe sets and 15 miRNAs were differentially expressed after surgery-induced weight loss. The clustering of similar expression patterns for gene products with related functions revealed molecular footprints that elucidate significant changes in cell cycle, development, lipid metabolism, and the inflammatory response. The participation of inflammation was demonstrated by results assessed in isolated adipocytes. Interestingly, when transcriptomes were analyzed taking into account the presence of miRNA target sites, miRNA target mRNAs were upregulated in obese AT (P value = 2 × 10(-181)) and inflamed adipocytes (P value = 4 × 10(-61)), according to the number of target sites harbored by each transcript. CONCLUSIONS: Current findings suggest impaired miRNA target gene expression in obese AT in close association with inflammation, both improving after weight loss.

Profiling of circulating microRNAs reveals common microRNAs linked to type 2 diabetes that change with insulin sensitization.

OBJECTIVE: This study sought to identify the profile of circulating microRNAs (miRNAs) in type 2 diabetes (T2D) and its response to changes in insulin sensitivity. RESEARCH DESIGN AND METHODS: The circulating miRNA profile was assessed in a pilot study of 12 men: 6 with normal glucose tolerance (NGT) and 6 T2D patients. The association of 10 circulating miRNAs with T2D was cross-sectionally validated in an extended sample of 45 NGT vs. 48 T2D subjects (65 nonobese and 28 obese men) and longitudinally in 35 T2D patients who were recruited in a randomized, double-blinded, and placebo-controlled 3-month trial of metformin treatment. Circulating miRNAs were also measured in seven healthy volunteers before and after a 6-h hyperinsulinemic-euglycemic clamp and insulin plus intralipid/heparin infusion. RESULTS: Cross-sectional studies disclosed a marked increase of miR-140-5p, miR-142-3p, and miR-222 and decreased miR-423-5p, miR-125b, miR-192, miR-195, miR-130b, miR-532-5p, and miR-126 in T2D patients. Multiple linear regression analyses revealed that miR-140-5p and miR-423-5p contributed independently to explain 49.5% (P < 0.0001) of fasting glucose variance after controlling for confounders. A discriminant function of four miRNAs (miR-140-5p, miR-423-5p, miR-195, and miR-126) was specific for T2D with an accuracy of 89.2% (P < 0.0001). Metformin (but not placebo) led to significant changes in circulating miR-192 (49.5%; P = 0.022), miR-140-5p (-15.8%; P = 0.004), and miR-222 (-47.2%; P = 0.03), in parallel to decreased fasting glucose and HbA1c. Furthermore, while insulin infusion during clamp decreased miR-222 (-62%; P = 0.002), the intralipid/heparin mixture increased circulating miR-222 (163%; P = 0.015) and miR-140-5p (67.5%; P = 0.05). CONCLUSIONS: This study depicts the close association between variations in circulating miRNAs and T2D and their potential relevance in insulin sensitivity.