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.

Oral Administration of Branched-Chain Amino Acids Attenuates Atherosclerosis by Inhibiting the Inflammatory Response and Regulating the Gut Microbiota in ApoE-Deficient Mice.

Atherosclerosis (AS) is a chronic inflammatory disease that serves as a common pathogenic underpinning for various cardiovascular diseases. Although high circulating branched-chain amino acid (BCAA) levels may represent a risk factor for AS, it is unclear whether dietary BCAA supplementation causes elevated levels of circulating BCAAs and hence influences AS, and the related mechanisms are not well understood. Here, ApoE-deficient mice (ApoE-/-) were fed a diet supplemented with or without BCAAs to investigate the effects of BCAAs on AS and determine potential related mechanisms. In this study, compared with the high-fat diet (HFD), high-fat diet supplemented with BCAAs (HFB) reduced the atherosclerotic lesion area and caused a significant decrease in serum cholesterol (TC) and low-density lipoprotein cholesterol (LDL-C) levels. BCAA supplementation suppressed the systemic inflammatory response by reducing macrophage infiltration; lowering serum levels of inflammatory factors, including monocyte chemoattractant protein-1 (MCP-1), tumor necrosis factor-α (TNF-α), interleukin-1ß (IL-1ß) and interleukin-6 (IL-6); and suppressing inflammatory related signaling pathways. Furthermore, BCAA supplementation altered the gut bacterial beta diversity and composition, especially reducing harmful bacteria and increasing probiotic bacteria, along with increasing bile acid (BA) excretion. In addition, the levels of total BAs, primary BAs, 12α-hydroxylated bile acids (12α-OH BAs) and non-12α-hydroxylated bile acids (non-12α-OH BAs) in cecal and colonic contents were increased in the HFB group of mice compared with the HFD group. Overall, these data indicate that dietary BCAA supplementation can attenuate atherosclerosis induced by HFD in ApoE-/- mice through improved dyslipidemia and inflammation, mechanisms involving the intestinal microbiota, and promotion of BA excretion.

Oral administration of branched-chain amino acids ameliorates high-fat diet-induced metabolic-associated fatty liver disease via gut microbiota-associated mechanisms.

Branched-chain amino acids (BCAAs), essential amino acids for the human body, are mainly obtained from food. High levels of BCAAs in circulation are considered as potential markers of metabolic-associated fatty liver disease (MAFLD) in humans. However, there are conflicting reports about the effects of supplement of BCAAs on MAFLD, and research on BCAAs and gut microbiota is not comprehensive. Here, C57BL/6J mice were fed with a high-fat diet with or without BCAAs to elucidate the effects of BCAAs on the gut microbiota and metabolic functions in a mouse model of MAFLD. Compared to high-fat diet (HFD) feeding, BCAA supplementation significantly reduced the mouse body weight, ratio of liver/body weight, hepatic lipid accumulation, serum levels of total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C) and alanine aminotransferase (ALT), and the expressions of the lipogenesis-related enzymes Fas, Acc, and Scd-1 and increased expressions of the lipolysis-related enzymes Cpt1A and Atgl in the liver. BCAAs supplementation also counteracted HFD-induced elevations in serum BCAAs levels by stimulating the enzymatic activity of BCKDH. Furthermore, BCAAs supplementation markedly improved the gut bacterial diversity and altered the gut microbiota composition and abundances, especially those of genera, in association with MAFLD and BCAAs metabolism. These data suggest that BCAA treatment improves HFD-induced MAFLD through mechanisms involving intestinal microbes.

Effect of dietary nucleotides on immune function in Balb/C mice.

This study investigated the effect of dietary nucleotides (NTs) on immune function in female Balb/C mice, which randomly distributed into six groups: one control group, one NF-free (NF) control group and four NT groups. NTs ranged from 0.0025% to 0.64%. Compared with the control group, the NF could significantly weaken the activity of T lymphocytes and macrophages, as well as decreased the activity of B lymphocytes and NK cell. NF significantly decreased the ratio of CD4(+)/CD8(+), whereas, it increased Tr percentage. In comparison with the NF group, the concentration of serum IL-2 and IL-4 showed an increase trend. Meanwhile, the granular cell macrophages colony stimulating factor (GM-CSF) increased significantly in the 0.04% NT group. The ratio of Th1/Th2 also showed an increasing trend after the supplements of NTs. There were no significant differences between the control and 0.04% NT group. Nevertheless, no significant differences in weight gain and lymphoid organ indices were observed in our study. These results indicate that NT supplements can prevent hypoimmunity which result from NF diet. 0.04% NTs is the healthy optimal supply proportion in mice diet.

Protective effect of a marine oligopeptide preparation from chum salmon (Oncorhynchus keta) on radiation-induced immune suppression in mice.

BACKGROUND: A marine oligopeptide preparation (MOP) obtained from Chum Salmon (Oncorhynchus keta) by the method of enzymatic hydrolysis, has been found to enhance the innate and adaptive immunities through stimulation of the secretion of cytokines in mice. The current study aimed to further investigate the protective effect of MOP on radiation-induced immune suppression in mice. RESULTS: Female ICR mice (6-8 weeks old) were randomly divided into three groups, i.e. blank control, irradiation control and MOP (1.350 g kg(-1) body weight) plus irradiation-treated group. MOP significantly increased the survival rate and prolonged the survival times for 30 days after irradiation, and lessened the radiation-induced suppression of T- or B-lymphocyte proliferation, resulting in the recovery of cell-mediated and humoral immune functions. This effect may be produced by augmentation of the relative numbers of radioresistant CD(4) (+) T cells, enhancement of the level of immunostimulatory cytokine, IL-12, reduction of the level of total cellular NF-κB through the induction of IκB in spleen and inhibition of the apoptosis of splenocytes. CONCLUSION: We propose that MOP be used as an ideal adjuvant therapy to alleviate radiation-induced injuries in cancer patients.

Ethanol exposure induces differential microRNA and target gene expression and teratogenic effects which can be suppressed by folic acid supplementation.

BACKGROUND: microRNAs (miRNAs) play an important role in development and are associated with birth defects. Data are scant on the role of miRNAs in birth defects arising from exposure to environmental factors such as alcohol. METHODS: In this study, we determined the expression levels of 509 mature miRNAs in fetal mouse brains with or without prenatal ethanol exposure using a miRNA microarray technique, verified by northern blot and PCR. Mouse embryos in culture were used to examine the effect of ethanol treatment on expression of the putative target genes of miR-10a (Hoxa1 and other Hox members) at mRNA and protein level. Open field and Morris water maze tests were also performed at post-natal day 35. RESULTS: Ethanol treatment induced major fetal teratogenesis in mice and caused mental retardation in their offspring, namely lower locomotor activity (P < 0.01) and impaired task acquisition. Of the screened miRNAs, miR-10a, miR-10b, miR-9, miR-145, miR-30a-3p and miR-152 were up-regulated (fold change >1.5) in fetal brains with prenatal ethanol exposure, whereas miR-200a, miR-496, miR-296, miR-30e-5p, miR-362, miR-339, miR-29c and miR-154 were down-regulated (fold change <0.67). Both miR-10a and miR-10b were significantly up-regulated (P < 0.01) in brain after prenatal ethanol exposure. Ethanol treatment also caused major obstruction in the development of cultured embryos, with down-regulated Hoxa1. Co-incubation with folic acid blocked ethanol-induced teratogenesis, with up-regulated Hoxa1 and down-regulated miR-10a (P < 0.01). CONCLUSIONS: The study provided new insights into the role of miRNAs and their target genes in the pathogenesis of fetal alcohol syndrome.

[Initial study of Hemp seeds protein on antifatigue and the immunomodulation effects in mice].

OBJECTIVE: To study the effects of Hemp seeds protein (HSP) on antifatigue and immunnomodulation effect in mice. METHODS: Female ICR mice at the ages of 6-8 weeks were administered with the HSP for 4 weeks at the dose of 1.32, 2.64 and 7.92 g/kg bw. After four weeks' treatment, the mice swimming time and some hiochemistry indexes were tested, such as blood lactic acid, BUN and hepatic glycogen, as well as the ratio of spleen and thymus organs index, the capacities of lymphocyte proliferation induced by ConA, DTH response, IgM-PFC number, the level of serum HC50, the indexes of the chicken red blood cells phagocytosis and the clearance rate of carbon particles were detected, and the ratio of CD4+ T helper (Th) cell in spleen were determined by the flow cytometer. RESULTS: In comparison with the control group, the HSP could improve the the swimming time and contents of liver hepatin distinctly, and reduced the contents of blood lactic acid. Then the capacities of lymphocyte proliferation induced by ConA, DTH response, IgM-PFC number, the level of serum HC50, the indexes of the clearance rate of carbon particles and the ratio of CD4+ T helper (Th) cell in spleen increased. CONCLUSION: HSP could have the ability of antifatigue and improve the immunomodulation effect in mice.

[Fundamental study on the cholesterol-lowering effect of whole turtle egg powder in SD rats].

OBJECTIVE: In order to study the cholesterol-lowering effects of whole turtle egg powder. METHODS: Fifty male SD rats were randomly divided into 5 groups according to body weight and serum cholesterol levels. They were fed one of five diets, a chow diet, a high fat supplemented diet (HF) and a HF diet supplemented with 0.75, 1.50 and or 3.00 g/kg BW whole turtle egg powder. After 24 weeks, collecting of the fecal and blood, serum total cholesterol (TC), high density lipoprotein cholesterol (HDL-C) and low density lipoprotein cholesterol (LDL-C) levels were determined by enzymic methods on an automatic analyzer. RESULTS: The serum TC levels were significantly decreased in both 1.50 g/kg BW group and 3.00 g/kg BW group compared with the HF rats (P < 0.05). Both 1.50 g/kg BW and 3.00 g/kg BW whole turtle egg powder increased fecal cholesterol, coprostanol and coprostanone excretion as well as total bile acids. CONCLUSION: The whole turtle egg powder lowered serum cholesterol by increasing the fecal steroids and turtle bile acids excretion.