cyanidin-3-o-beta-glucopyranoside and Non-alcoholic-Fatty-Liver-Disease

Cyanidin-3-O-β-glucoside (Cy-3-G) the most abundant monomer of anthocyanins has multiple protective effects on many diseases. To date, whether Cy-3-G could regulate the function of brown adipose tissue (BAT) is still unclear and whether this regulation could influence the secretion of adipokines from BAT to prevent non-alcoholic fatty liver disease (NAFLD) indirectly remains to be explored. In this study we investigated the effect of Cy-3-G on BAT and the potential role of Cy-3-G to prevent fatty liver through regulating the secretion of BAT.. Male C57BL/6 J mice were fed with a high fat high cholesterol (HFC) diet with or without 200 mg/kg B.W Cy-3-G for 8 weeks. In in vitro experiments, the differentiated brown adipocytes (BAC) and C3H10T1/2 clone8 cells were treated with 0.2 mM palmitate with or without Cy-3-G for 72 or 96 h. Then the culture media of C3H10T1/2 clone8 cells were collected for measuring the adipokines secretion by immunoblot assay and were applied to culture HepG2 cells or LO2 cells for 24 h. Lipid accumulation in HepG2 cells or LO2 cells were evaluated by oil red O staining.. Here we found that Cy-3-G regulated the activation of BAT and the expression of adipokines in BAT which were disrupted by HFC diet and alleviated diet induced fatty liver in mice. In in vitro experiments, Cy-3-G inhibited the release of adipokines including extracellular nicotinamide phosphoribosyltransferase (eNAMPT) and fibroblast growth factor 21 (FGF21) from differentiated C3H10T1/2 clone8 cells induced by palmitate, which was accompanied by a reduction of lipid accumulation in HepG2 cells and LO2 cells cultured by the corresponding collected media of C3H10T1/2 clone8 cells.. These results indicate that Cy-3-G can regulate the thermogenic and secretory functions of BAT. Furthermore, our data suggest that the protective effect of Cy-3-G on hepatic lipid accumulation is probably via regulating the secretion of adipokines from BAT.

Topics: Adipocytes; Adipokines; Adipose Tissue, Brown; Animals; Anthocyanins; Cell Differentiation; Diet, High-Fat; Disease Models, Animal; Glucosides; Hep G2 Cells; Humans; Male; Mice, Inbred C57BL; Non-alcoholic Fatty Liver Disease; Protective Agents

Obesity develops when energy intake exceeds energy expenditure. Promoting brown adipose tissue (BAT) formation and function increases energy expenditure and may protect against obesity. Cyanidin-3-glucoside (C3G) is an anthocyanin compound that occurs naturally in many fruits and vegetables. In this study, we investigated the effect and mechanism of C3G on the prevention of obesity.. Db/db mice received C3G dissolved in drinking water for 16 wk; drinking water served as the vehicle treatment. The total body weight, energy intake, metabolic rate, and physical activity were measured. The lipid droplets, gene expression and protein expression were evaluated by histochemical staining, real-time PCR, and western blots. We found that C3G increased energy expenditure, limited weight gain, maintained glucose homeostasis, reversed hepatic steatosis, improved cold tolerance, and enhanced BAT activity in obese db/db mice. C3G also induces brown-like adipocytes (beige) formation in subcutaneous white adipose tissue (sWAT) of db/db mice model. We also found that C3G potently regulates the transcription of uncoupling protein 1 (UCP1) both in BAT and sWAT through increasing mitochondrial number and function.. Our results suggest that C3G plays a role in regulating systemic energy balance, which may have potential therapeutic implications for the prevention and control of obesity.

Topics: Adipogenesis; Adipose Tissue, Brown; Adipose Tissue, White; Animals; Anthocyanins; Behavior, Animal; Dietary Supplements; Energy Intake; Energy Metabolism; Gene Expression Regulation; Glucosides; Liver; Locomotion; Male; Mice, Mutant Strains; Microscopy, Electron, Transmission; Mitochondria; Non-alcoholic Fatty Liver Disease; Obesity; Thermotolerance; Uncoupling Protein 1; Up-Regulation; Whole Body Imaging

Increased consumption of dark-coloured fruits and vegetables may mitigate metabolic syndrome. This study has determined the changes in metabolic parameters, and in cardiovascular and liver structure and function, following chronic administration of either cyanidin 3-glucoside (CG) or Queen Garnet plum juice (QG) containing cyanidin glycosides to rats fed either a corn starch (C) or a high-carbohydrate, high-fat (H) diet. Eight to nine-week-old male Wistar rats were randomly divided into six groups for 16-week feeding with C, C with CG or QG, H or H with CG or QG. C or H were supplemented with CG or QG at a dose of ∼ 8 mg/kg/day cyanidin glycosides from week 8 to 16. H rats developed signs of metabolic syndrome including visceral adiposity, impaired glucose tolerance, hypertension, cardiovascular remodelling, increased collagen deposition in left ventricle, non-alcoholic fatty liver disease, increased plasma liver enzymes and increased inflammatory cell infiltration in the heart and liver. Both CG and QG reversed these cardiovascular, liver and metabolic signs. However, no intact anthocyanins or common methylated/conjugated metabolites could be detected in the plasma samples and plasma hippuric acid concentrations were unchanged. Our results suggest CG is the most likely mediator of the responses to QG but that further investigation of the pharmacokinetics of oral CG in rats is required.

Topics: Animals; Anthocyanins; Cardiovascular System; Diet, High-Fat; Dietary Carbohydrates; Dietary Fats; Dietary Supplements; Fruit and Vegetable Juices; Glucosides; Hypertension; Liver; Male; Metabolic Syndrome; Non-alcoholic Fatty Liver Disease; Prunus domestica; Rats; Rats, Wistar

Apoptosis is an early event of steatohepatitis in non-alcoholic fatty liver disease (NAFLD), and an increase in oxidative stress induced by hyperglycemia has been linked to an acceleration of apoptosis in hepatocytes. Cyanidin-3-O-β-glucoside (C3G), a classic anthocyanin, has been reported to reduce oxidative stress and attenuate non-alcoholic steatohepatitis in mice. In this study, we evaluated the toxicity of high glucose in primary hepatocytes of mice fed with a high fat diet and amelioration of this toxicity by C3G. Incubation of hepatocytes with 35mM glucose for 12h resulted in a significant decrease in cell viability and increase in apoptotic cell death. Furthermore, hyperglycemia-induced mitochondrial depolarization was accompanied by the release of cytochrome c and altered expression of Bax and Bcl-2, suggesting a mitochondria-mediated apoptotic mode of cell death. Pre-incubation with 50μM C3G induced changes associated with better cell survival and function, including a reduction in reactive species generation, improvement of mitochondrial membrane potential, inactivation of caspase-3 and -9, and down-regulation of the pro-apoptotic Bax protein. We further investigated the role of the phosphatidylinositol 3-kinase (PI3K)/Akt and mitogen-activated protein kinases (MAPKs) pathways with respect to the anti-apoptotic action of C3G, and our results showed that C3G could activate Akt. Additionally, C3G inactivated c-Jun N-terminal protein kinase (JNK), but not extracellular signal-regulated kinase or p38 MAPK, in glucose-stressed cells. Interestingly, JNK inhibitor enhanced the protective effect of C3G on cell survival. Our results suggest that anthocyanin C3G may exhibit hepatoprotective potential against NAFLD by promoting functional integrity and survival of hepatocytes.

Topics: Animals; Anthocyanins; Apoptosis; bcl-2 Homologous Antagonist-Killer Protein; bcl-2-Associated X Protein; Cytochromes c; Diet, High-Fat; Dietary Fats; Fatty Liver; Gene Expression Regulation; Glucose; Glucosides; Hepatocytes; JNK Mitogen-Activated Protein Kinases; Male; Membrane Potential, Mitochondrial; Mice; Mitochondria; Non-alcoholic Fatty Liver Disease; p38 Mitogen-Activated Protein Kinases; Phosphatidylinositol 3-Kinase; Primary Cell Culture; Protein Kinase Inhibitors; Proto-Oncogene Proteins c-akt; Signal Transduction