Choline and trimethylamine N-oxide supplementation in normal chow diet and western diet promotes the development of atherosclerosis in Apoe -/- mice through different mechanisms.

Trimethylamine N-oxide (TMAO), a gut microbiota-dependent metabolite, has been shown to aggravate cardiovascular disease. However, the mechanisms of TMAO in the setting of cardiovascular disease progress remain unclear. Here, we aim to investigate the effects of TMAO on atherosclerosis (AS) development and the underlying mechanisms. Apoe -/- mice received choline or TMAO supplementation in a normal diet and a western diet for 12 weeks. Choline or TMAO supplementation in both normal diet and western diet significantly promoted plaque progression in Apoe-/- mice. Besides, serum lipids levels and inflammation response in the aortic root were enhanced by choline or TMAO supplementation. In particular, choline or TMAO supplementation in the western diet changed intestinal microbiota composition and bile acid metabolism. Therefore, choline or TMAO supplementation may promote AS by modulating gut microbiota in mice fed with a western diet and by other mechanisms in mice given a normal diet, even choline or TMAO supplementation in a normal diet can promote AS.

Specific Metabolites Involved in Antioxidation and Mitochondrial Function Are Correlated With Frailty in Elderly Men.

BACKGROUND: As an age-related syndrome, frailty may play a central role in poor health among older adults. Sarcopenia overlaps with the physical domain of frailty, and most existing studies have analyzed the associated factors of frailty and sarcopenia as an isolated state. Perturbations in metabolism may play an important role in the presence of frailty or sarcopenia; however, the metabolites associated with frailty, especially overlapping with sarcopenia remain unclear. In this study, we aimed to explore whether amino acids, carnitines, acylcarnitines and lysophosphatidylcholines, as specific panels, are significantly correlated with frailty, especially overlapping with sarcopenia, to gain insight into potential biomarkers and possible biological mechanisms and to facilitate their management. METHODS: We applied a targeted high-performance liquid chromatography-tandem mass spectrometry approach in serum samples from 246 Chinese older men (age 79.2 ± 7.8 years) with frailty (n = 150), non-frailty (n = 96), frailty and sarcopenia (n = 52), non-frail and non-sarcopenic control (n = 85). Frailty was evaluated using Freid phenotype criteria, sarcopenia was defined by diagnostic algorithm of Asian Working Group on Sarcopenia, and the participants were diagnosed as frailty and sarcopenia when they met the evaluation criteria of both frailty and sarcopenia. A panel of 29 metabolomic profiles was assayed and included different classes of amino acids, carnitines, acylcarnitines, and lysophosphatidylcholines (LPCs). Multivariate logistic regression was used to screen the metabolic factors contributing to frailty status, and orthogonal partial least squares discriminant analysis was used to explore important factors and distinguish different groups. RESULTS: In older men demonstrating the frail phenotype, amino acid perturbations included lower tryptophan and higher glycine levels. With regard to lipid metabolism, the frailty phenotype was characterized by lower concentrations of isovalerylcarnitine (C5), LPC16:0 and LPC18:2, while higher levels of octanoyl-L-carnitine (C8), decanoyl-L-carnitine (C10), dodecanoyl-L-carnitine (C12) and tetradecanoyl-L-carnitine (C14). After adjusting for several clinical confounders, tryptophan, LPC18:2, LPC 16:0 and C5 were negatively correlated with frailty, and C8 and C12 were positively related to frailty. We preliminarily identified metabolic profiles (LPC16:0, LPC18:2, glycine and tryptophan) that may distinguish older men with frailty from those without frailty. Importantly, a set of serum amino acids and LPCs (LPC16:0, LPC18:2, and tryptophan) was characterized in the metabotype of older adults with an overlap of frailty and sarcopenia. The metabolites that were most discriminating of frailty status implied that the underlying mechanism might be involved in antioxidation and mitochondrial dysfunction. CONCLUSIONS: These present metabolic analyses may provide valuable information on the potential biomarkers and possible biological mechanisms of frailty, and overlapping sarcopenia. The findings obtained may offer insight into their management in older adults.

Caffeic acid prevents non-alcoholic fatty liver disease induced by a high-fat diet through gut microbiota modulation in mice.

Caffeic acid (CA) is derived from many plants and may have the ability to reduce hepatic lipid accumulation. The gut microbiota produces lipopolysaccharides and further influences hepatic lipid metabolism, and thus plays an important role in the development of nonalcoholic fatty liver disease (NAFLD). However, whether the beneficial effects of CA are associated with the gut microbiota remains unclear. The present study aimed to investigate the benefits of experimental treatment with CA on the gut microbiota and metabolic functions in a mouse model of NAFLD. In this study, C57BL/6J mice received a high-fat diet (HFD) for 8 weeks and were then fed a HFD supplemented with or without CA for another 8 weeks. HFD induced obesity and increased accumulation of intrahepatic lipids, serum biochemical parameters and gene expression related to lipid metabolism. Microbiota composition was determined via 16S rRNA sequencing, and analysis revealed that HFD led to dysbiosis, accompanied by endotoxemia and low-grade inflammation. CA reverted the imbalance in the gut microbiota and related lipopolysaccharide-mediated inflammation, thus inhibiting deregulation of lipid metabolism-related gene expression. Our results support the possibility that CA can be used as a therapeutic approach for obesity-associated NAFLD via its anti-inflammatory and prebiotic integrative response.

[The lipid-lowering and antioxidative effects of marine collagen peptides].

OBJECTIVE: To determine the relative molecular mass of marine collagen peptides (MCPs) and investigate the effects of MCPs on serum lipids, anti-oxidative enzymes and malondialdehyde (MDA) in hyperlipidemic rats. METHODS: Sephadex G-25, high performance liquid chromatography (HPLC) and matrix-assisted laser desorption ionization time of flight mass spectrometry (MALDI-TOF-MS) methods were used to determine the relative molecular mass of MCPs. Then 50 healthy male SD rats were divided into 5 groups, which were normal control (NC) group, hyperlipidemic model control (HC) group and 1.0, 3.0, 9.0 g/kgbw MCPs groups, MCPs were orally administered by gavage to rats in MCPs group for 45 consecutive days (2 ml/100 kgbw per day), and the control rats were given vehicle only, all animals (except NC rats) were fed with a high fat diet composed of 79% basic diet, 10% lard, 10% yolk powder and 1% cholesterol. The levels of serum lipids, the content of MDA and activity of superoxide dismutase (SOD), glutathione peroxidase (GSH-Px) in serum were measured. RESULTS: The levels of serum total cholesterol (TC) in 1.0, 3.0, 9.0 g/kgbw MCPs groups were 1.89 +/- 0.29, 2.07 +/- 0.39 and 1.99 +/- 0.29 mmol/L respectively, each of which was significantly lower than that in HC group (3.37 +/- 0.24 mmol/L); low-density lipoprotein cholesterol (LDL-C) levels in 1.0, 3.0, 9.0 g/kgbw MCPs groups were 0.83 +/- 0.16, 1.01 +/- 0.35 and 0.91 +/- 0.26 mmol/L respectively, each of which was significantly lower than that in HC group(2.20 +/- 0.34 mmol/L); triglyceride (TG) levels in 3.0 and 9.0 g/kgbw MCPs groups (0.90 +/- 0.15 and 0.86 +/- 0.12 mmol/L) were reduced significantly compared with that in HC group (1.18 +/- 0.18 mmol/L); MDA level in 9.0 g/kgbw MCPs group was 7.1 +/- 4.1 nmol/ml, which was significantly lower than that in HC group ( 15.9 +/- 9.9 nmol/ml); and atherogenic index (AI) in hyperlipidemic rats fed with 1.0, 3.0, 9.0 g/kgbw MCPs were 1.14 +/- 0.22, 1.16 +/- 0.27 and 0.99 +/- 0.31 respectively, each of which was significantly lower than that in HC group (2.27 +/- 0.55). The activities of SOD in 1.0, 3.0, 9.0 g/kgbw MCPs groups (218.6 +/- 33.2, 242.7 +/- 21.4 and 242.1 +/- 44.8 U/ml) were obviously increased compared with that in HC group (119.7 +/- 47.8 U/ml), and anti-atherogenic index (AAI) were also increased significantly (0.47 +/- 0.04, 0.47 +/- 0.06, 0.51 +/- 0.09 vs 0.31 +/- 0.05). CONCLUSION: MCPs should have antioxidative and lipid-lowering effects, and might play a preventive role in hyperlipidemia and atherogenesis.

[Effects of marine collagen peptide on delaying the skin aging].

OBJECTIVE: To investigate the protective effect of marine collagen peptides (MCPs) on the skin of aged mice induced by D-galactose. METHODS: Subchronic toxicity study was conducted while D-galactose induced subacute aging model was established. D-galactose dose of 0.125 g/kg body weight was intraperitoneally injected daily for 90 days. Marine collagen peptide 0.225, 0.450, 1.350 g/kg body weight were administered by oral gavage. Superoxide dismutase (SOD), catalase (CAT) activity and malondialdehyde (MDA) content in blood serum were measured, along with cutaneous histopathology examination. RESULTS: Epidermal thickness was significantly higher in MCPs treated group. Number and activity of fibroblast in MCPs treated dermis was increased prominently. The activity of SOD in 0.225, 0.450, 1.350 g/kgbw MCPs treated groups were 455.52 +/- 11.39, 460.15 +/- 18.09, 468.59 +/- 27.25 U/ml respectively, each of which was significantly higher than that in model control group; the activity of serum CAT in 0.225, 1.350 g/kgbw MCPs treated groups (21.33 +/- 4.82, 21.69 +/- 1.68 U/ml) were obviously increased compared with that in model control group (17.14 +/- 2.81 U/ml); MDA level in 0.450, 1.350 g/kgbw MCPs treated groups were 5.67 +/- 0.93, 5.76 +/- 1.02 nmol/ml respectively, each of which was significantly lower than that in model control group (7.63 +/- 1.37 nmol/ml). CONCLUSIONS: The results showed that MCPs might play a protective role on skin aging by improving the activity of antioxidant.