Oat fiber supplementation alleviates intestinal inflammation and ameliorates intestinal mucosal barrier via acting on gut microbiota-derived metabolites in LDLR-/- mice.

OBJECTIVE: Gut microbiota-derived metabolites are involved in intestinal inflammation, which can affect the development of atherosclerotic plaques. Previous studies have shown that oat fiber can delay the progression of atherosclerosis via improving lipid metabolism. The aim of this study was to evaluate how oat fiber acted on gut microbiota-derived metabolites, inhibited intestinal inflammation, and protected the intestinal mucosal barrier. METHODS: Male low-density lipoprotein receptor knock-out (LDLR-/-) mice were fed a high-fat/cholesterol diet with or without oat fiber for 14 wk. Histopathology of the aorta was detected by Oil Red O staining, and the small intestine mucosal pathology was measured through hematoxylin and eosin staining. Non-targeted metabolomics of feces was performed using liquid chromatography-mass spectrometry. Western blot method was used to assess the relative levels of the proteins involved in the toll-like receptor (TLR)4 signal pathway and intestinal mucosal barrier in interest tissues. RESULTS: Pathologically, oat fiber reversed the increment of the atherosclerotic lesion and ameliorated intestinal mucosal barrier in LDLR-/- mice. Oat fiber regulated the levels of gut microbiota-derived metabolites along with a decrease in isobutyrylcarnitine, valerylcarnitine, 1-methylguanosine, and 2-methylguanosine, and an increase in l-tyrosine and niacinamide. Notably, oat fiber blocked the TLR4 signal pathway and decreased the expression of nuclear factor-κB p65 in both the aorta and gut tissues. Also, oat fiber raised the expression of tight junction proteins including ZO-1 and occludin. CONCLUSION: Taken together, the present study revealed that oat fiber feeding effectively attenuated the development of atherosclerosis, at least partly via affecting gut microbiota-derived metabolites, inhibiting the intestinal inflammatory response, and maintaining the integrity of the intestinal mucosal barrier.

Lipolysis and thermogenesis in adipose tissues as new potential mechanisms for metabolic benefits of dietary fiber.

OBJECTIVE: Dietary fiber consumption is associated with reduced risk for the development of noncommunicable diseases. The aim of the present study was to evaluate the effects of cereal dietary fiber on the levels of proteins involved in lipolysis and thermogenesis in white adipose tissue (WAT) and brown adipose tissue (BAT) of C57 BL/6 J mice fed a high-fat diet (HFD). METHODS: Male C57BL/6 J mice were fed normal chow diet (Chow), HFD, HFD plus oat fiber (H-oat), or HFD plus wheat bran fiber (H-wheat) for 24 wk. Body weight and food intake were recorded weekly. Serum adiponectin was assayed by an enzyme-linked immunosorbent assay kit. Western blotting was used to assess the protein expressions of adipose triacylglycerol lipase (ATGL), cAMP protein kinase catalytic subunit (cAMP), protein kinase A (PKA), perilipin A, hormone-sensitive lipase (HSL), uncoupling protein 1 (UCP1), fibroblast growth factor 21 (FGF-21), ß3-adrenergic receptor (ß3AR), and proliferator-activated receptor gamma coactivator-1 α (PGC-1 α) in the WAT and BAT. RESULTS: At the end of the feeding period, body and adipose tissues weight in both H-oat and H-wheat groups were lower than in the HFD group. Mice in the H-oat and H-wheat groups showed an increasing trend in serum adiponectin level. Compared with the HFD group, cereal dietary fiber increased protein expressions involved in the lipolysis and browning process. Compared with the H-wheat group, H-oat was more effective in protein expressions of PKA, PGC-1 α, and UCP1 of the WAT samples. Compared with the H-oat group, H-wheat was more effective in protein expressions of PKA, ATGL, UCP1, ß3AR, and FGF-21 of the BAT samples. CONCLUSIONS: Taken together, our results suggested that cereal dietary fiber enhanced adipocyte lipolysis by the cAMP-PKA-HSL pathway and promoted WAT browning by activation of UCP1, and consequently reduced visceral fat mass in response to HFD feeding.

Chronic leucine supplementation improves lipid metabolism in C57BL/6J mice fed with a high-fat/cholesterol diet.

BACKGROUND: Leucine supplementation has been reported to improve lipid metabolism. However, lipid metabolism in adipose tissues and liver has not been extensively studied for leucine supplementation in mice fed with a high-fat/cholesterol diet (HFCD). DESIGN: C57BL/6J mice were fed a chow diet, HFCD, HFCD supplemented with 1.5% leucine (HFCD+1.5% Leu group) or 3% leucine (HFCD+3% Leu group) for 24 weeks. The body weight, peritoneal adipose weight, total cholesterol (TC), triglyceride in serum and liver, and serum adipokines were analyzed. In addition, expression levels of proteins associated with hepatic lipogenesis, adipocyte lipolysis, and white adipose tissue (WAT) browning were determined. RESULTS: Mice in the HFCD group developed obesity and deteriorated lipid metabolism. Compared with HFCD, leucine supplementation lowered weight gain and TC levels in circulation and the liver without changing energy intake. The decrease in body fat was supported by histological examination in the WAT and liver. Furthermore, serum levels of proinflammatory adipokines, such as leptin, IL-6, and tumor necrosis factor-alpha, were significantly decreased by supplemented leucine. At the protein level, leucine potently decreased the hepatic lipogenic enzymes (fatty acid synthase and acetyl-coenzyme A carboxylase) and corresponding upstream proteins. In epididymal WAT, the reduced expression levels of two major lipases by HFCD, namely phosphorylated hormone-sensitive lipase and adipose triglyceride lipase, were reversed when leucine was supplemented. Uncoupling protein 1, ß3 adrenergic receptors, peroxisome proliferator-activated receptor g coactivator-1α, and fibroblast growth factor 21 were involved in the thermogenic program and WAT browning. Leucine additionally upregulated their protein expression in both WAT and interscapular brown adipose tissue. CONCLUSION: This study demonstrated that chronic leucine supplementation reduced the body weight and improved the lipid profile of mice fed with a HFCD. This beneficial effect was ascribed to hepatic lipogenesis, adipocyte lipolysis, and WAT browning.

Effects of cereal fiber on leptin resistance and sensitivity in C57BL/6J mice fed a high-fat/cholesterol diet.

BACKGROUND: Cereal fiber is reported to be associated with obesity and metabolic diseases. However, whether cereal fiber improves leptin resistance and sensitivity remains unclear. DESIGN: For 24 weeks, 48 male C57BL/6J mice were randomly given a normal chow diet (Chow), high-fat/cholesterol diet (HFD), HFD with 0.8% oat fiber (H-oat) or HFD with 0.8% wheat bran fiber (H-wheat). At the end of feeding period, both the serum insulin and leptin levels were determined by ELISA kits. Western blotting was used to assess the protein expressions of the leptin receptor (LepR) and the leptin-signaling pathway in the adipose tissues. RESULTS: Our results suggested that mice fed oat or wheat bran fiber exhibited lower body weight, serum lipids, as well as insulin and leptin levels. The two cereal fibers potently increased the protein expressions of LepR in the adipose tissue. In addition, protein expressions of Janus kinase 2 (JAK2) and transcription 3 (STAT3) (induced by LepR), which enhances leptin signaling, were significantly higher and the expression of cytokine signaling-3 (SOCS3), which inhibits leptin signaling, was significantly lower in the two cereal fiber groups than in the HFD group. CONCLUSION: Taken together, our findings suggest that cereal fiber can improve leptin resistance and sensitivity by the JAK2/STAT3 pathway in C57BL/6J mice fed a HFD; furthermore, oat fiber is more effective in the improvement of leptin sensitivity than wheat bran fiber, in this murine model.

Whole-grain intake and total, cardiovascular, and cancer mortality: a systematic review and meta-analysis of prospective studies.

BACKGROUND: The potential role of whole grain in preventing various mortality outcomes has been inconsistently reported in a wealth of prospective observational studies. OBJECTIVE: We evaluated the relations between whole-grain intake and risks of dying from any cause, cardiovascular disease (CVD), and cancer through a meta-analytic approach. DESIGN: Relevant studies were identified by searching PubMed and EMBASE databases and bibliographies of retrieved full publications. Summary RRs with 95% CIs were calculated with a random-effects model. RESULTS: Thirteen studies on total mortality (104,061 deaths), 12 on CVD mortality (26,352 deaths), and 8 on cancer mortality (34,797 deaths) were included. Three studies reported whole-grain intake, and the remaining studies reported whole-grain product intake. In the dose-response analysis in which the intake of whole-grain products was converted to the amount of whole grain, the summary RRs for an increment in whole-grain intake of 50 g/d were 0.78 (95% CI: 0.67, 0.91) for total mortality, 0.70 (95% CI: 0.61, 0.79) for CVD mortality, and 0.82 (95% CI: 0.69, 0.96) for cancer mortality. A similar reduction was observed for the mortality from ischemic heart disease (RR: 0.68; 95% CI: 0.55, 0.84) but not from stroke (RR: 0.93; 95% CI: 0.54, 1.62). There was evidence of nonlinear associations of whole-grain intake with total (P-nonlinearity < 0.001) and CVD mortality (P-nonlinearity <0.001), but not with cancer mortality (P-nonlinearity = 0.12), with the curves for the associations appearing slightly steeper at lower ranges (<35 g/d) of the intake than at higher ranges. CONCLUSIONS: Our findings suggest significant inverse relations between whole-grain intake and mortality due to any cause, CVD, or cancer. The findings support the recommendation of increasing whole-grain intake to improve public health.

Dairy products consumption and metabolic syndrome in adults: systematic review and meta-analysis of observational studies.

The association of dairy products consumption with risk of metabolic syndrome (MetS) has been inconsistently reported in observational studies. A systematic review and meta-analysis of published observational studies was conducted to quantitatively evaluate this association. Relevant studies were identified by searching PubMed and EMBASE databases and by carefully checking the bibliographies of retrieved full reports and related reviews. Eligible studies were observational studies that investigated the association between dairy products consumption and risk of MetS in adults, with risk estimates available. Random-effects model was assigned to calculate the summary risk estimates. The final analysis included 15 cross-sectional studies, one case-control study and seven prospective cohort studies. Higher dairy consumption significantly reduced MetS by 17% in the cross-sectional/case-control studies (odds ratio = 0.83, 95% confidence interval [CI], 0.73-0.94), and by 14% (relative risk [RR] = 0.86, 95% CI, 0.79-0.92) in cohort studies. The inverse dairy-MetS association was consistent in subgroup and sensitivity analyses. The dose-response analysis of the cohort studies conferred a significant 6% (RR = 0.94, 95% CI, 0.90-0.98) reduction in the risk of MetS for each increment in dairy consumption of one serving/d. No significant publication bias was observed. Our findings suggest an inverse dose-response relationship between dairy consumption and risk of MetS.

Leucine supplementation improves leptin sensitivity in high-fat diet fed rats.

BACKGROUND: Several studies have reported the favorable effect of leucine supplementation on insulin resistance or insulin sensitivity. However, whether or not leucine supplementation improves leptin sensitivity remains unclear. DESIGN: Forty-eight male Sprague-Dawley rats were fed with either a high-fat diet (HFD) or HFD supplemented with 1.5, 3.0, and 4.5% leucine for 16 weeks. At the end of the experiment, serum leptin level was measured by ELISA, and leptin receptor (ObR) in the hypothalamus was examined by immunohistochemistry. The protein expressions of ObR and leptin-signaling pathway in adipose tissues were detected by western blot. RESULTS: No significant differences in body weight and food/energy intake existed among the four groups. Serum leptin levels were significantly lower, and ObR expression in the hypothalamus and adipose tissues was significantly higher in the three leucine groups than in the control group. These phenomena suggested that leptin sensitivity was improved in the leucine groups. Furthermore, the expressions of JAK2 and STAT3 (activated by ObR) were significantly higher, and that of SOCS3 (inhibits leptin signaling) was significantly lower in the three leucine groups than in the control group. CONCLUSIONS: Leucine supplementation improves leptin sensitivity in rats on HFD likely by promoting leptin signaling.

Dairy consumption and risk of cardiovascular disease: an updated meta-analysis of prospective cohort studies.

BACKGROUND: Epidemiological studies to-date provided inconsistent findings on the effects of dairy consumption on the risk of cardiovascular disease (CVD). We aimed to examine the association of dairy consumption and its specific subtypes with CVD risk, including the risk of stroke and coronary heart disease (CHD) by a metaanalysis. METHODS: PubMed, EMBASE, and Cochrane Library databases were searched for articles published up to February 2014 to identify prospective cohort studies. Random-effects model or fix-effects model was used to compute the summary risk estimates. RESULTS: A total of 22 studies were eligible for analysis. An inverse association was found between dairy consumption and overall risk of CVD [9 studies; relative risk (RR)=0.88, 95% confidence interval (CI): 0.81, 0.96] and stroke (12 studies; RR=0.87, 95% CI: 0.77, 0.99). However, no association was established between dairy consumption and CHD risk (12 studies; RR=0.94, 95% CI: 0.82, 1.07). Stroke risk was significantly reduced by consumption of low-fat dairy (6 studies; RR=0.93, 95% CI: 0.88, 0.99) and cheese (4 studies; RR=0.91, 95% CI: 0.84, 0.98), and CHD risk was significantly lowered by cheese consumption (7 studies; RR=0.84, 95% CI: 0.71, 1.00). Restricting studies according to various inclusion criteria yielded similar results for CVD and CHD analyses, but showed attenuated results for stroke analysis. Heterogeneity across studies was found for stroke and CHD analyses, and publication bias was found for stroke analysis. CONCLUSION: This meta-analysis provided further evidence supporting the beneficial effect of dairy consumption on CVD. Low-fat dairy products and cheese may protect against stroke or CHD incidence.

Effect of vitamin D supplementation on the level of circulating high-sensitivity C-reactive protein: a meta-analysis of randomized controlled trials.

Vitamin D might elicit protective effects against cardiovascular disease by decreasing the level of circulating high-sensitivity C-reactive protein (hs-CRP), an inflammatory marker. Thus, we conducted a meta-analysis of randomized controlled trials to evaluate the association of vitamin D supplementation with circulating hs-CRP level. A systematic literature search was conducted in September 2013 (updated in February 2014) via PubMed, Web of Science, and Cochrane library to identify eligible studies. Either a fixed-effects or a random-effects model was used to calculate pooled effects. The results of the meta-analysis of 10 trials involving a total of 924 participants showed that vitamin D supplementation significantly decreased the circulating hs-CRP level by 1.08 mg/L (95% CI, -2.13, -0.03), with the evidence of heterogeneity. Subgroup analysis suggested a higher reduction of 2.21 mg/L (95% CI, -3.50, -0.92) among participants with baseline hs-CRP level ≥5 mg/L. Meta-regression analysis further revealed that baseline hs-CRP level, supplemental dose of vitamin D and intervention duration together may be attributed to the heterogeneity across studies. In summary, vitamin D supplementation is beneficial for the reduction of circulating hs-CRP. However, the result should be interpreted with caution because of the evidence of heterogeneity.

Vitamin D intake and risk of type 1 diabetes: a meta-analysis of observational studies.

Vitamin D is suggested to have protective effects against type 1 diabetes. However, the results from observational studies have been inconsistent. We aimed to examine their association by conducting a meta-analysis of observational studies. Multiple databases were searched in June 2013 to identify relevant studies including both case-control and cohort studies. Either a fixed- or random-effects model was used to calculate the pooled risk estimate. We identified eight studies (two cohort studies and six case-control studies) on vitamin D intake during early life and three studies (two cohort studies and one case-control study) on maternal vitamin D intake during pregnancy. The pooled odds ratio for type 1 diabetes comparing vitamin D supplementation with non-supplementation during early life was 0.71 (95% confidence interval [CI], 0.51-0.98). Similar results were observed in the case-control subgroup analysis but not in the cohort subgroup analysis. The pooled odds ratio with maternal intake of vitamin D during pregnancy was 0.95 (95% CI, 0.66-1.36). In conclusion, vitamin D intake during early life may be associated with a reduced risk of type 1 diabetes. However, there was not enough evidence for an association between maternal intake of vitamin D and risk of type 1 diabetes in the offspring.

Protective potentials of wild rice (Zizania latifolia (Griseb) Turcz) against obesity and lipotoxicity induced by a high-fat/cholesterol diet in rats.

The study evaluates the protective potentials of wild rice against obesity and lipotoxicity induced by a high-fat/cholesterol diet in rats. In addition to the rats of low-fat diet group, others animals were exposed to a high-fat/cholesterol diet condition for 8 weeks. The city diet (CD) is based on the diet consumed by urban residents in modern China, which is rich in fat/cholesterol and high in carbohydrates from white rice and processed wheat starch. The chief source of dietary carbohydrates of wild rice diet (WRD) is from Chinese wild rice and other compositions are the same with CD. Rats fed CD showed elevated body and liver organ weights, lipid profiles, free fatty acids (FFA) and leptin comparable with rats fed high-fat/cholesterol diet (HFD) known to induce obesity and hyperlipidaemia in this species. However, rats consuming WRD suppressed the increase of lipid droplets accumulation, FFA, and leptin, and the decrease of lipoprotein lipase and adipose triglyceride lipase. Meanwhile, WRD prevented high-fat/cholesterol diet-induced elevation in protein expression of sterol-regulatory element binding protein-1c, and gene expression of fatty acid synthase and acetyl-CoA carboxylase. These findings indicate that wild rice as a natural food has the potentials of preventing obesity and liver lipotoxicity induced by a high-fat/cholesterol diet in rats.

[Influences of compound whole grain on oxidative stress to hyperlipidemia population].

OBJECTIVE: To explore the influence of compound whole grain complex antioxidant chain on oxidative stress to the hyperlipidemia population. METHODS: From March 2008 to March 2009, 418 hyperlipemia residents (45 to 75 years of age) of Han group were screened from 3 main districts in Nanjing, according to the community, blood lipids and oxidative indicators, stratified into intervention and control group by quasi-experimental design. The intervention group (212 individuals) were provided with compound whole grain and health education while only health education was provided for the control group (206 individuals). Body mass index (BMI), waist-to-hip ratio (WHR), total cholesterol (TC), triglyceride (TG) and high density lipoprotein cholesterol (HDL-C) and oxidative indicators (including T-AOC, MDA, SOD, GSH-Px) were measured before and after the one-year intervention period. Analyses of the correlation between posture, biochemical markers and oxidative stress indicators before and after intervention were carried out. RESULTS: After intervention, BMI ((25.53 ± 2.77) kg/m(2)), WHR (0.82 ± 0.03), TC ((4.60 ± 0.98) mmol/L), TG ((1.26 ± 0.88) mmol/L) in the intervention group were decreased significantly compared to the levels of BMI ((26.60 ± 3.18) kg/m(2)), WHR (0.93 ± 0.05), TC ((4.97 ± 1.02) mmol/L), TG ((1.98 ± 1.11) mmol/L) in the control group (all P values < 0.05); while HDL-C ((1.34 ± 0.26) mmol/L) in the intervention group was increased significantly compared to the level of HDL-C ((1.18 ± 0.17) mmol/L) in the control group (P < 0.05); After intervention, levels of T-AOC (19.52 ± 0.81), SOD ((85.42 ± 21.65) U/ml) and GSH-Px ((128.26 ± 33.65) µmol/L) were increased significantly compared to the levels of T-AOC (11.11 ± 1.30), SOD ((78.68 ± 30.48) U/ml) and GSH-Px ((118.48 ± 24.19) µmol/L) in the control group (all P values < 0.05); while MDA ((1.78 ± 1.16) nmol/ml) decreased significantly compared to the level of MDA ((2.12 ± 1.37) nmol/ml in the control group (P < 0.05); Pearson product moment correlation analysis showed that: T-AOC with TC, TG, BMI showed a negative correlation (r values were -0.258, -0.266, -0.230, respectively, all P values < 0.05), while with HDL-C was a positive correlation (r values was 0.194, P < 0.05); SOD with TC, TG, BMI showed a negative correlation (r values were -0.282, -0.311, -0.217, respectively, all P values < 0.05), while with HDL-C was a positive correlation (r values was 0.169, P < 0.05). CONCLUSION: Compound whole grain could improve lipid metabolism to the hyperlipidemia population. There was a correlation between common human metabolism and the levels of oxidative stress.

[The dynamic changing profiles of peripheral white blood cell telomere length in populations of different ages living at different altitude areas].

OBJECTIVE: To investigate the relationship between the length of telomere DNA and age at different altitude areas. METHODS: All 172 peripheral blood samples were randomly selected from healthy individuals of different ages from 25 to 65 years old. High altitude group (47 males, 48 females) living at an altitude of 4380 m (HA group), sea level group (39 males, 38 females) living at an altitude of 43 m (SL group). The terminal restriction fragment (TRF) length of telomere DNA was measured by Southern blotting analysis. The plasma levels of malondialdehyde (MDA) and superoxide dismutase (SOD) were assayed. RESULTS: Average TRF lengths of males and females in HA groups were 10.45 +/- 1.35 and 10.50 +/- 1.45. Average TRF lengths of males and females in SL groups were 11.29 +/- 1.10 and 11.31 +/- 1.13. A negative correlation was shown between the average TRF length and age of males in two groups (P < 0.01). This was also the case for females. ANOVA test was used to analyze the difference between TRF length and gender at different ages (P < 0.001). It was shown that there was significant difference in TRF length between the male (25 years old and 55 years old) and female (25 years old and 55 years old) in two groups at different ages (P < 0.05). The plasma levels of SOD and MDA were significant different between HA groups and SL groups (25-44 years old groups/45-65 years old groups) (P < 0.05). CONCLUSION: Obviously shortening of telomere was observed by increasing of ages in high altitude groups. There was a negative correlation between the length of telomere DNA and ages. Telomere shortening became more obviously in high altitude group than in sea level group in keeping with the age increases.