Mangiferin Treatment Inhibits Hepatis Expression Of Acyl-Coenzyme A:Diacylglycerol Acyltransferase-2 In Fructose-Fed Spontaneously Hypertensive Rats:a Link To Amelioration Of Fatty Liver

Objective:Mangiferin, a xanthone glucoside, is an effective active ingredient which is extracted from mango leaves. Its associated traditional herbs have been demonstrated to improve abnormalities of lipid metabolism. However, its underlying mechanisms remain largely unclear. This study investigated the molecular mechanisms of MA in fructose-fed spontaneously hypertensive rats(SHRs).Methods:1. Select 24 SHRs, were randomly divided into four groups according to the average weight(n=6 per group):(1) water control, free access to water(2) fructose control, free access to 10% fructose solution(w/v, preparation every day)(3) fructose+mangiferin 5 mg/kg/d(4) fructose+mangiferin 15 mg/kg/d In order to exclude the influence resulting from differences in fructose intake, fructose consumption in the groups treated with mangiferin were adjusted by regulating the concentration of fructose solution per 3 days to match that of the fructose control group on the previous days.2. In the seventh week, after 14 hours of fasting, rats were weighed and killed by prompt dislocation of the neck vertebra. Liver was collected and weighed.3. Detected TC, TQ GLU, NEFA, Insulin, ALT and AST content in plasma.4. Detect TG, TC content of liver.5. Detect the liver SREBP-1c, CHREBP, LPK, ACC-1, FAS, SCD-1, DGAT-1, DGAT-2, PPAR-α, CPT1a, ACO, CD36; IR, IRS-1, IRS-2, collagen I, MCP-1 and TNF-α gene expression.6. Detect the liver SREBP-1c, CHREBP, SCD-1, DGAT-1 and DGAT-2 protein expression.Result:1. General indicators:After seven weeks, compared with CON group, the amount of FRU food intake was significantly decreased, but body weight has no significant difference. Compared with FRU group, MA had no significant effect on food intake and body weight.2. Biochemical indicators:Compared with CON group, FRU group significantly increased plasma levels of TG and NEFA, while other indicators have no significant difference. Compared with FRU group, MA had no significant effect on TC, TG, glucose, insulin and NEFA.3. Liver-related indicators:Compared with CON group, FRU group decreased liver weight, while the content of liver TG is significant increased. However, plasma ALT, AST and liver TC are no significant changed. Compared with FRU group, MA (15mg/kg/d) decreased triglyceride content.4. The genetic test results:Compared with CON group, the fructose activates expression of liver MTTP and SCD-1 gene, which other genes did not change significantly. MA (15mg/kg/d) distinctly diminished DGAT-2 mRNA levels, it had no change on MTTP and SCD-1 mRNA levels.5. Western blot results:Compared with CON group, fructose consumption strongly stimulated SCD-1 and DGAT-2 at the protein levels, which it did not significantly change nuclear SREBP1c, nuclear CHREBP and DGAT-1 protein levels. MA (15mg/kg/d) significantly inhibited DGAT-2, but not SCD-1 at the protein levels.Conclusion:1. MA (15mg/kg/d) ameliorates fatty liver in fructose-fed SHR.2. MA (15mg/kg/d) ameliorates fatty liver in fructose-fed SHR by inhibiting hepatic DGAT-2.