Betaine attenuates age-related suppression in autophagy via Mettl21c/p97/VCP axis to delay muscle loss.

Age-related impairment of autophagy accelerates muscle loss and lead to sarcopenia. Betaine can delay muscle loss as a dietary methyl donor via increasing S-adenosyl-L-methionine (SAM, a crucial metabolite for autophagy regulation) in methionion cycle. However, whether betaine can regulate autophagy level to attenuate degeneration in aging muscle remains unclear. Herein, male C57BL/6J young mice (YOU, 2-month-old), old mice (OLD, 15-month-old), and 2%-betaine-treated old mice (BET, 15-month-old) were employed and raised for 12 weeks. All mice underwent body composition examination and grip strength test before being sacrificed. Betaine alleviated age-related decline in muscle mass and strength. Meanwhile, betaine preserved the expression autophagy markers (Atg5, Atg7, LC3-II, and Beclin1) both at transcriptional and translational level during the aging process. RNA-sequencing results generated from mice gastrocnemius muscle found Mettl21c, a SAM-dependent autophagy-regulating methyltransferase, was significantly higher expressed in BET and YOU group. Results were further validated by qPCR and western bloting. In vitro, C2C12 cells with or without Mettl21c RNA interference were treated different concentration of betaine (0 mM, 10 mM) under methionine-starved condition. Compared with control group, betaine upregulated autophagy markers expression and autophagy flux. By increasing the SAM level, betaine facilitated trimethylation of p97 (Mettl21c downstream effector) into valosin-containing protein (VCP). Increased VCP promoted autophagic turnover of cellular components, ATP production, and cell differentiation. Knock-down of Metthl21c dismissed improvements mentioned above. Collectively, betaine could enhance aged skeletal muscle autophagy level via Mettl21c/p97/VCP axis to delay muscle loss.

Calorie restriction on normal body weight mice prevents body weight regain on a follow-up high-fat diet by shaping an obesity-resistant-like gut microbiota profile.

Calorie restriction (CR) is one of the most common approaches for obesity treatment, but whether resuming ad libitum feeding after CR in normal-weight mice can affect excessive weight regain remains poorly studied. To address this issue, male C57BL/6 mice were placed in three groups: a control group (n = 10), a group fed normal diet with 30% CR (n = 20); and a group fed a HF diet (n = 30). After four weeks, the CR group was fed either a normal diet (NDCR, n = 10) or a high-fat diet (HFCR, n = 10) for an additional eight weeks. At the end of the experiment, mice in the HF group ranked in the upper and lower thirds for weight gain were designated as obesity-prone (HFOP, n = 10) and obesity-resistant (HFOR, n = 10), respectively. CR delayed weight regain and visceral fat accumulation. Gut microbiota in the HFCR group were more similar to the HFOR group than the HFOP group, mainly due to reversion of the decreased level of Clostridiales induced by CR. Mediation analysis showed that Clostridiales may delay body weight regain by affecting the interconversion of succinate and fumarate. Random forest and structural equation analyses showed Christensenellaceae were the most important biomarker for alleviation of obesity. In conclusion, CR shapes an obesity-resistant-like gut microbiota profile that may attenuate body weight regain.

Enteromorpha prolifera polysaccharide prevents high- fat diet-induced obesity in hamsters: A NMR-based metabolomic evaluation.

Enteromorpha prolifera polysaccharide (EP) has been shown to exhibit hypolipidemic and hypoglycemic activities in various experimental models. Here, an 1 H-NMR-based metabolomic study was conducted to explore the regulatory effects of EP on serum metabolic changes in obese hamsters. High-fat diet (HFD)-fed hamsters were orally administrated with EP (300, 450, or 600 mg/kg) once daily for 12 weeks. Compared with HFD-fed hamsters, EP treatment (450 and 600 mg/kg) significantly decreased the body weight (by 8.69 and 8.24%), liver weight (by 7.87 and 8.25%), epididymal white adipose tissue (by 19.54 and 17.26%), perirenal white adipose tissue (by 28.09 and 28.94%), serum total cholesterol (by 24.31 and 18.61%), triglyceride (by 30.64 and 31.38%), and low-density lipoprotein cholesterol (by 38.26 and 36.30%), respectively. In addition, EP intervention also significantly decreased hepatic cholesterol (by 23.20, 38.16, and 34.57%) and triglyceride content (by 17.78, 41.47, and 35.50%) as well as serum levels of alanine aminotransferase (ALT) and ALT/aspartate aminotransferase (AST) ratio. The serum samples of normal diet (ND) group, HFD group and HFD + EP 450 mg/kg (HFD + MEP) group were further analyzed by 1 H-NMR spectroscopy. Compared with ND group, 17 and 2 metabolites were significantly upregulated and downregulated in HFD group, respectively. Interestingly, EP treatment significantly downregulated nine metabolites and upregulated one metabolite when compared to those in HFD group. Our results indicated that EP intervention partially ameliorated HFD-induced metabolic dysfunction, and the most prominent metabolic pathways included citrate cycle, synthesis and degradation of ketone bodies, pyruvate metabolism, valine, leucine and isoleucine degradation, and arginine biosynthesis. PRACTICAL APPLICATION: Enteromorpha prolifera polysaccharide (EP), the main active component of Enteromorpha prolifera, is reported to have many biological activities. However, the antiobesity effect of EP and its corresponding metabolic mechanism have not been reported so far. The results of this study confirmed the antiobesity effect of EP on HFD-induced obese hamsters and elucidated its possible metabolic mechanism. Our study highlighted that EP might be used in weight-loss functional foods.

Temporal cross-correlations between air pollutants and outpatient visits for respiratory and circulatory system diseases in Fuzhou, China.

BACKGROUND: Previous studies have suggested that there is an association between air pollutants and circulatory and respiratory diseases; however, relatively few have analyzed the association between air pollutants and outpatient visits based on the mortality, hospitalization rates, etc., especially in areas with relatively good air quality. Therefore, we conducted this study to research the association between air pollutants and outpatient visits in Fuzhou, China. METHODS: We used a generalized linear Poisson model to study the association between air pollution and outpatient visits for respiratory and circulatory diseases from 2016 to 2018 in Fuzhou, China. RESULTS: In the single pollutant model, nitrogen dioxide (NO2) had a significant effect. For lag day 0 to lag day 5, the effect decreased with every 10 µg/L increase in NO2. The daily maximum 8-h mean ozone (O3-8h) and upper respiratory outpatient visits were positively associated during the cold period [lag2, excess risk (ER) (95% confidence interval (CI)): 1.68% (0.44-2.94%)], while O3-8h and respiratory disease were positively associated during the warm period [lag5, ER (95% CI): 1.10% (0.11-2.10%) and lag4, ER (95% CI): 1.02% (0.032-2.02%)]. Similarly, particulate matter (PM) with an average aerodynamic diameter of less than 10 µm (PM10) and lower respiratory diseases were positively associated during the warm period [lag0, ER (95% CI): 1.68% (0.44-2.94%)]. When the concentration of O3-8h was higher than 100 µg/L, there was a positive effect on circulatory [lag5, ER (95% CI): 2.83% (0.65-5.06%)], respiratory [lag5, ER (95% CI): 2.47% (0.85-4.11%)] and upper respiratory [lag5, ER (95% CI): 3.06% (1.38-4.77%)] outpatient visits. The variation in O3-8h changed slightly when we adjusted for other air pollutants, and after adjusting for O3-8h, the ERs of the other air pollutants changed slightly. After adjusting for PM with an average aerodynamic diameter of less than 2.5 µm (PM2.5), the ERs of the other air pollutants increased, and after adjusting for NO2, the ER of PM decreased. CONCLUSION: Exposure to ambient NO2, O3, PM2.5 and PM10 was associated with an increase in respiratory and circulatory system-related outpatient visits in Fuzhou, China.