The association of alcohol consumption with the risk of sarcopenia: a dose-response meta-analysis.

Background: Sarcopenia is defined as a progressive loss of skeletal muscle mass plus a decline in muscle strength and/or reduced physical performance with advancing age. The results of current studies on the relationship between drinking and sarcopenia remain controversial.Objectives: The aim of this meta-analysis was to evaluate the association of alcohol consumption with the risk of sarcopenia.Methods: Systematic searches were conducted without language restrictions from the beginning of each database to September 20, 2023 on PubMed, Embase, Cochrane Library, Web of Science, Wanfang Data, Chinese BioMedical Literature, and China national knowledge infrastructure databases. Meta-analysis was conducted to pool the study-specific odds ratios (ORs) with 95% confidence interval (CI).Results: Sixty-two studies with 454,643 participants were enrolled. The meta-analysis of proportions revealed that alcohol consumption was not associated with the presence of sarcopenia, with a pooled OR of 0.964 (95% CI = 0.912-1.019). Further subgroup analysis indicated that alcohol consumption was correlated with lower risk of sarcopenia in men (OR = 0.763; 95% CI = 0.622-0.938; P = .010). The nonlinear dose-response analysis suggested a J-shaped association between alcohol consumption and the risk of sarcopenia, with a nadir at the amounts of alcohol consumption of 6.6 grams/day (OR = 0.765; 95% CI = 0.608-0.957; P < .05).Conclusions: The results of this meta-analysis indicate that alcohol consumption is not a risk factor for the development of sarcopenia. Any suggestion of a putative protective effect of alcohol should be treated with caution, particularly in light of the overall lack of relationship reported in the present comprehensive meta-analysis.

Serum Meteorin-like is associated with weight loss in the elderly patients with chronic heart failure.

BACKGROUND: Unintentional weight loss (cachexia) has been associated with poor outcomes in chronic heart failure (CHF). Meteorin-like (Metrnl) is a novel myokine with protective effects on cardiovascular diseases. However, the change of Metrnl concentrations and its role in elderly patients with CHF remains unclear. The aim of this study was to evaluate the association of serum Metrnl with weight loss and outcomes in elderly patients with CHF. METHODS: A total of 931 consecutive elderly patients (aged 60 years and older) with CHF and 135 age-matched and sex-matched control subjects were enrolled. Serum Metrnl concentration was measured by enzyme-linked immunosorbent assay. Body weight was measured at baseline and 12 months. RESULTS: Median of serum Metrnl levels was lower in CHF patients when compared with controls [201.31 (184.95-261.16) pg/mL vs. 168.68 (103.15-197.54) pg/mL, P < 0.001]. Patients with the lowest levels of Metrnl had higher N-terminal pro brain natriuretic peptide (NT-proBNP) levels but lower left ventricular eject fraction (LVEF) and estimated glomerular filtration rate (P < 0.001). Lower serum Metrnl was associated with a higher risk of >5% weight loss from baseline to 12 months [odds ratio = 6.13, 95% confidence interval (CI) = 2.57-14.62 per log decrease; P < 0.001]. Serum Metrnl levels were decreased as LVEF decreased (P < 0.001) and were positively correlated with LVEF (r = 0.267, P < 0.001) but negatively correlated with NT-proBNP levels (r = -0.257, P < 0.001). Cox regression analysis suggested that lower serum Metrnl was associated with higher cardiovascular mortality [hazard ratio (HR) = 6.71, 95% CI = 3.41-13.18 per log decrease; P < 0.001], CHF rehospitalization (HR = 3.07, 95% CI = 1.82-5.17 per log decrease; P < 0.001), and the combined major adverse cardiac event(s) (MACEs) (HR = 5.38, 95% CI = 3.51-8.25 per log decrease; P < 0.001). The Kaplan-Meier survival curves showed that low concentration of Metrnl was a prognostic indicator of MACEs in patients with CHF. CONCLUSIONS: Our study suggests that lower serum Metrnl level is correlated with weight loss and the severity of cardiac dysfunction in elderly patients with CHF.

Trimetazidine attenuates dexamethasone-induced muscle atrophy via inhibiting NLRP3/GSDMD pathway-mediated pyroptosis.

Skeletal muscle atrophy is one of the major side effects of high dose or sustained usage of glucocorticoids. Pyroptosis is a novel form of pro-inflammatory programmed cell death that may contribute to skeletal muscle injury. Trimetazidine, a well-known anti-anginal agent, can improve skeletal muscle performance both in humans and mice. We here showed that dexamethasone-induced atrophy, as evidenced by the increase of muscle atrophy F-box (Atrogin-1) and muscle ring finger 1 (MuRF1) expression, and the decrease of myotube diameter in C2C12 myotubes. Dexamethasone also induced pyroptosis, indicated by upregulated pyroptosis-related protein NLR family pyrin domain containing 3 (NLRP3), Caspase-1, and gasdermin-D (GSDMD). Knockdown of NLRP3 or GSDMD attenuated dexamethasone-induced myotube pyroptosis and atrophy. Trimetazidine treatment ameliorated dexamethasone-induced muscle pyroptosis and atrophy both in vivo and in vitro. Activation of NLRP3 using LPS and ATP not only increased the cleavage and activation of Caspase-1 and GSDMD, but also increased the expression levels of atrophy markers MuRF1 and Atrogin-1 in trimetazidine-treated C2C12 myotubes. Mechanically, dexamethasone inhibited the phosphorylation of PI3K/AKT/FoxO3a, which could be attenuated by trimetazidine. Conversely, co-treatment with a PI3K/AKT inhibitor, picropodophyllin, remarkably increased the expression of NLRP3 and reversed the protective effects of trimetazidine against dexamethasone-induced C2C12 myotube pyroptosis and atrophy. Taken together, our study suggests that NLRP3/GSDMD-mediated pyroptosis might be a novel mechanism for dexamethasone-induced skeletal muscle atrophy. Trimetazidine might be developed as a potential therapeutic agent for the treatment of dexamethasone-induced muscle atrophy.