•The HFD diet drives the elevation of IL-17A and exacerbates the steatosis in mice.•IL-17A inhibits fatty acid oxidation in vitro and in vivo.•IL-17A decreases the expression of PPARα through the JNK pathway.There is a growing body of evidence that the interleukin-17A (IL-17A) signaling pathway contributes to the pathogenesis of nonalcoholic fatty liver disease (NAFLD). However, the mechanism by which IL-17A signaling induces hepatocyte injury is unclear. The aim of the present study was to investigate the significance of the IL-17A axis in NAFLD and to explore the role of IL-17A in high-fat diet (HFD)-induced NAFLD in C57BL/6 mice and oleic acid (OA)-induced lipid accumulation in hepatocytes. Firstly, Consistent upregulation of IL-17A was observed in the HFD-induced steatosis mice but not the normal chow-fed control mice. Administration of IL-17A impaired liver function, aggravated hepatic lipid accumulation by inhibiting fatty acid oxidation in the HFD mice. Conversely, inhibition of IL-17A using an anti-IL-17A monoclonal antibody (mAb) significantly attenuated HFD-induced liver injury. Furthermore, IL-17A accelerated hepatic steatosis through activation of the JNK-PPARα pathway in the HFD mice and OA-preloaded hepatocytes.ConclusionThe present study demonstrated that a high fat diet induces IL-17A expression, which exacerbates the progression of NAFLD by inhibiting fatty acid β-oxidation and promoting the accumulation of triglycerides (TG).Download high-res image (97KB)Download full-size image

Previous studies indicated that cyanidin-3-O-β-glucoside (C3G) as a classical anthocyanin exerted an anti-fibrotic effect in the liver, but its bioavailability was quite low. This study was undertaken to explore the restraining effect of C3G and its metabolite protocatechuic acid (PCA) on the activation of hepatic stellate cells (HSCs). Our data demonstrated that the treatment of a carbon tetrachloride-treated mice model with C3G inhibited liver fibrosis and HSC activation. In vitro, both C3G and PCA preserved the lipid droplets and retinol in primary HSCs, and additionally inhibited the mRNA expression of α-smooth muscle actin and collagen I, but elevated the level of matrix metalloproteinase-2 and liver X receptors. Only PCA suppressed the levels of tumor necrosis factor alpha (TNF-α) and interleukin-6 (IL-6) secreted from HSCs significantly. In addition, C3G and PCA inhibited the proliferation and migration of HSCs. In conclusion, PCA mainly explained the in vivo inhibiting effect of C3G on HSC activation and liver fibrosis.

The beneficial effects of fish oil consumption on glucose metabolism have been generally reported. However, the mechanism underlying the fish oil-induced protective effects against insulin resistance remains unclear. Endoplasmic reticulum (ER) stress is recognized as an important contributor to insulin resistance. The aim of this study is to evaluate whether fish oil supplementation reduces ER stress and ameliorates insulin resistance in diet-induced obese mice, and to investigate the molecular mechanism of fish oil-induced benefits on ER stress. C57BL/6J mice were fed one of the following diets for 12 weeks: the low-fat diet (LFD), the high-fat diet (HFD) or the fish oil-supplemented high-fat diet (FOD). Fish oil supplementation led to lower blood glucose, better glucose tolerance and improved insulin sensitivity in high-fat diet-induced obese mice. Importantly, fish oil administration inhibited high-fat feeding-induced ER stress and reduced adipose tissue dysfunction. The fish oil-induced improvements were accompanied by the elevation of phosphorylated AMP-activated protein kinase (AMPK) expression in white adipose tissue. Correspondingly, the results of in vitro experiments showed that docosahexaenoic acid (DHA), the main n-3 polyunsaturated fatty acid (PUFA) in the fish oil used in the study, led to a dose-dependent increase in AMPK phosphorylation and suppressed palmitic acid (PA)-triggered ER stress in differentiated 3T3-L1 adipocytes. Furthermore, AMPK inhibitor (compound C) treatment largely blocked the effects of DHA to inhibit PA-induced ER stress. Our data indicate that n-3 PUFAs suppress ER stress in adipocytes through AMPK activation, and may thereby exert protective effects against high-fat feeding-induced adipose tissue dysfunction and insulin resistance.

The berries of bilberry and black currant are a rich source of anthocyanins, which are thought to have favorable effects on nonalcoholic steatohepatitis (NASH). This study was designed to examine whether purified anthocyanins from bilberry and black currant are able to limit the disorders related to NASH induced by a methionine-choline-deficient (MCD) diet in mice. The results showed that treatment with anthocyanins not only alleviated inflammation, oxidative stress, steatosis, and even fibrosis but also improved depletion of mitochondrial content and damage of mitochondrial biogenesis and electron transfer chain developed concomitantly in the liver of mice fed the MCD diet. Furthermore, anthocyanins treatment promoted activation of AMP-activated protein kinase (AMPK) and expression of peroxisome proliferator-activated receptor-gamma coactivator-1α (PGC-1α). These data provide evidence that anthocyanins possess significant protective effects against NASH and mitochondrial defects in response to a MCD diet, with a mechanism maybe through affecting the AMPK/PGC-1α signaling pathways.

This study investigated whether cyanidin-3-O-β-glucoside (Cy-3-G), a predominant anthocyanin, could exert a protective role on liver injury and its further mechanisms of the anti-fibrosis actions in mice. The results demonstrated that the treatment of Cy-3-G (800 mg/kg diet) for 8 weeks significantly attenuated hepatotoxicity and fibrosis in carbon tetrachloride (CCl4) administered mice. Cy-3-G strongly down-regulated the expression of α-smooth muscle actin (α-SMA), desmin, and matrix metalloproteinase (MMPs), which showed its suppression effect on the activation of hepatic stellate cells (HSCs). In addition, Cy-3-G favorably regulated oxidative stress and apoptosis in liver. Furthermore, Cy-3-G ameliorated the infiltration of inflammatory cells such as neutrophils and leukocytes and meanwhile suppressed the production of pro-inflammatory cytokines and growth factors. In conclusion, daily intake of Cy-3-G could prevent liver fibrosis progression in mice induced by CCl4 through inhibiting HSC activation, which provides a basis for clinical practice of liver fibrosis prevention.

With the dramatically increasing prevalence of obesity and type 2 diabetes mellitus (T2DM) worldwide, there is an urgent need for new strategies to combat the growing epidemic of these metabolic diseases. Diet is an essential factor affecting the development of and risk for obesity and T2DM and it can either help or hurt. In searching for preventative and therapeutic strategies, it is therefore advantageous to consider the potential of certain foods and their bioactive compounds to reverse or prevent the pathogenic processes associated with metabolic disease. Anthocyanins are naturally occurring polyphenolic compounds abundant in dark-colored fruits, vegetables and grains. Epidemiological studies suggest that increased consumption of anthocyanins lowers the risk of T2DM. Many in vitro and in vivo studies also reveal an array of mechanisms through which anthocyanins could prevent or reverse obesity- and T2DM-related pathologies including promotion of antioxidant and anti-inflammatory activities, improvement of insulin resistance, and hypolipidemic and hypoglycemic actions. Here, we summarize the data on anthocyanin-mediated protection against obesity and T2DM and the underlying mechanisms. Further population-based and long-term human intervention studies are necessary to ultimately evaluate the use of anthocyanins for protection/prevention against the development of obesity and T2DM.

The concentrations of heavy metals in both local environmental samples (water and crops) and in the whole blood of 1,152 local residents were determined by atomic absorption spectrometry. We calculated rate ratios and standardized mortality ratios based on age-, gender-, and cause-specific mortality for both the district and province. Multi-regression models were then used to evaluate the associations between the exposure to multiple heavy metals and cause-specific mortality in the studied population. Significant increases in the mean concentrations of cadmium, lead, and zinc in the blood samples were found to be associated with a substantially elevated all-cancer mortality rate in this high-exposure area (HEA). There were also significantly elevated mortality rates in the HEA for both sexes from a wide range of causes (all-cause), including cardiovascular disease (CVD), when compared with a low-exposure area (LEA). Further analysis showed positive correlations between exposure to both cadmium and lead and a higher risk of all-cancer mortality among women and for both sexes combined. In contrast, zinc exposure negatively correlated with the risk of cause-specific mortality, but this was not significant. These results of our current study thus reveal that long-term environmental exposure to both cadmium and lead is associated with an increased risk of all-cause, CVD, and all-cancer mortality, whereas zinc exposure showed a possible weak protection against death from CVD.

Polyphenols, including anthocyanins, from various plant foods are effective in the prevention of atherosclerosis in animal and human studies. Protocatechuic acid (PCA), a major metabolite of anthocyanins, has been found to possess the anti-carcinogenic effect, whereas the in vivo effect of PCA as an anti-atherosclerotic agent remains unknown. We demonstrated herein that PCA inhibited monocyte adhesion to tumor necrosis factor-α (TNF-α)-activated mouse aortic endothelial cells, associated with the inhibition of vascular cell adhesion molecule 1 (VCAM-1) and intercellular adhesion molecule 1 (ICAM-1) expression. Furthermore, PCA inhibited the nuclear content of p65, a subunit of nuclear factor-κB (NF-κB), along with reduced NF-κB binding activity. Finally, PCA administration in the apolipoprotein E (ApoE)-deficient mouse model reduced aortic VCAM-1 and ICAM-1 expression, NF-κB activity, and plasma-soluble VCAM-1 and ICAM-1 levels, with inhibiting atherosclerosis development. We suggest that PCA possesses the anti-atherogenic effect at least partially via its anti-inflammatory activity.

Lycopene has antioxidant, anticancer, and anti-inflammatory effects with molecular mechanisms not fully identified.We investigated the effects of lycopene on the inflammatory responses to lipopolysaccharide (LPS) in RAW264.7 cells and the signal transduction pathways involved.Lycopene inhibited LPS-induced production of nitric oxide (NO) and interleukin-6 (IL-6) with decreased mRNAs of inducible nitric oxide synthase and IL-6 but had no effect on TNF-α. Further study showed that lycopene also inhibited LPS-induced IκB phosphorylation, IκB degradation, and NF-κB translocation. Moreover, lycopene blocked the phosphorylation of ERK1/2 and p38 MAP kinase but not c-Jun NH2-terminal kinase. To confirm the causal link between MAP kinase inhibition and its anti-inflammatory effects, we treated the cells with SB 203580 and U0126. These inhibitors significantly inhibited LPS-induced NO and IL-6 formation.Lycopene inhibits the inflammatory response of RAW 264.7 cells to LPS through inhibiting ERK/p38 MAP kinase and the NF-κB pathway.

As a common phytochemical, cyanidin 3-O-β-glucoside (C3G) has a role in inhibiting inflammatory mediators; however, its mechanism of action remains unclear. The purpose of this study was to explore the effect of C3G on lipopolysaccharide (LPS)-stimulated TNFα and IL-6 expression in the human monocyte/macrophage cell line THP-1, and to explore the mechanisms involved.Differentiated THP-1 cells were treated with different concentrations of C3G (0.005, 0.05, 0.5,10 μM) in the absence or presence of 1 ng/mL LPS. mRNA expression levels were detected by real time PCR, and secretion of TNFα and IL-6, phosphorylated IκBα, and nuclear factor-kappa B (NF-κB) P65 were monitored by ELISA or Western blotting analysis. The role of an inhibitor of IκBα phosphorylation, BAY 11-7082, in C3G inhibition of LPS-induced cytokines expression was investigated.C3G (0.05–0.5 μM) treatment significantly inhibited LPS-stimulated TNFα and IL-6 mRNA expression and secretion of these proteins by THP-1 cells. Phosphorylation of IκBα and NF-κB nuclear translocation could be blocked by 0.5 μM C3G. BAY 11-7082 treatment abolished C3G-induced reduction of TNFα and IL-6.Our results suggest that C3G exerts its anti-inflammatory effect through inhibiting IκBα phosphorylation, thereby suppressing NF-κB activity in THP-1 cells.

This study was designed to evaluate the effect of an anthocyanin-rich extract from black rice on hyperlipidemia and insulin resistance in fructose-fed rats. Rats fed fructose diet for 4 weeks exhibited significantly higher plasma insulin levels and lower insulin sensitivity than the control rats fed AIN-93G diet. Dietary supplementation with the anthocyanin-rich extract (5 g/kg of high-fructose diet) prevented the development of fructose-induced insulin resistance. After fructose-induced insulin resistance had been established, 4-week treatment with the anthocyanin-rich extract (5 g/kg of high-fructose diet) or pioglitazone (270 mg/kg of high-fructose diet) ameliorated the glucose intolerance and hyperlipidemia, but the extract failed to reverse the fructose-induced hyperinsulinemia as pioglitazone did. In addition, rats supplemented by the extract exhibited lower oxidative stress than the fructose-fed controls, as indicated by the lower concentrations of plasma thiobarbituric acid reactive substances and blood oxidized glutathione. Overall, these results suggest that the anthocyanin-rich extract from black rice improves certain metabolic abnormalities associated with diets high in fructose.

BackgroundThe scientific evidence for the association of daily flavonoid and stilbene intakes with cardiovascular risk factors in Chinese adults has not been reported previously.ObjectiveThe aim of the study was to assess daily flavonoid and stilbene intakes and evaluate these compounds' association with cardiovascular risk factors such as serum lipids and carotid intima–media thickness in Chinese adults.DesignA total of 1,393 subjects participated in this cross-sectional study from July 2008 to January 2010 in China. Dietary flavonoid and stilbene intakes as well as overall dietary intakes from foods and beverages were assessed with a quantitative food frequency questionnaire. Anthropometric measurements and cardiovascular risk factors including serum lipids, uric acid, and carotid intima–media thickness were examined. The relationship between flavonoids and stilbene intakes and these cardiovascular risk factors was examined using either partial correlation coefficients or analysis of covariance.ResultsThe richest sources of flavonoids and stilbenes were the fruit group including apple, plum, pear, and peach, followed by the vegetable group containing lotus root and taro. The daily intake of total flavonoids, anthocyanidins, flavonols, flavones, isoflavones, and stilbene were 165.6 mg/day, 27.6 mg/day, 123.7 mg/day, 10.7 mg/day, 3.7 mg/day, and 0.3 mg/day, respectively. Higher daily consumption of anthocyanidins was associated with elevated serum high-density lipoprotein cholesterol (HDL-C) concentrations (P trend=0.001), and higher total flavonoid and flavonol intakes were associated with lower serum triglycerides (TG) concentrations (P trend=0.020 and P trend=0.035, respectively) and TG/HDL-C ratios (P trend=0.040 and P trend=0.045, respectively) in female subjects. These significant relationships were not found in male subjects.ConclusionsThe daily intakes of flavonoid and stilbene were estimated in the present study, and higher dietary flavonoid intake was associated with improving lipid profile in Chinese women. The results indicate that dietary flavonoids may have beneficial effect on preventing cardiovascular diseases.

BackgroundFemale injecting drug users who are sex workers (IDUFSWs) are at high risk of contracting HIV. They may bridge HIV transmissions from injecting drug users to clients of female sex workers.MethodsA total of 216 non-institutionalised IDUFSWs were recruited by snowball sampling methods. Anonymous face-to-face interviews were conducted to collect data. Univariate, multivariate and hierarchical logistic regression models were fitted to investigate the associations between background characteristics, cognitive variables, psychological stress and syringe sharing behaviours among IDUFSWs.ResultsRespectively 33.8% and 27.8% of the respondents injected drugs with others’ used syringes and gave used syringes to others for drug injection in the last month. These two syringe sharing behaviours were significantly associated with inconsistent condom use during commercial sex (OR = 5.00 and 1.92, p < 0.05). Over 90% of the respondents reported at least one type(s) of psychological distress included in this study. Adjusting for significant background variables, all variables that are related to the Theory of Planned Behaviour (attitude, norm, perceived control and behavioural intention) and psychological distress (except for depression) were significantly associated with injecting drugs with others’ used syringes (adjusted OR = 2.08–6.25, p < 0.05), whilst variables related to perceived control, behavioural intention and insomnia were significantly associated with providing used syringes to others for injection (adjusted OR = 2.00–3.56, p < 0.05). In two separate summary multivariate models, variables related to the Theory of Planned Behaviours and psychological distress were independently associated with injecting drugs with others’ used syringes (OR = 1.98–4.02, p < 0.05) and giving used syringes to others for injection (OR = 2.06–3.59, p < 0.05).ConclusionsSyringe sharing behaviours were prevalent among IDUFSWs and were associated with cognitive and psychological factors. Effective integrative intervention programmes targeting IDUFSWs are warranted.