Mechanism Of 6-gingerol Alleviates High Fructose-induced Insulin Resistance In Rats

Objective This study investigated the action effect and elementary mechanism of 6-gingerol on the insulin resistance in fructose-fed rats.Methods 24 rats were divided into 4 groups according to body weight(n=6): control group,fructose group,fructose + 6-gingerol(50 ?g/kg)and fructose + 6-gingerol(200?g/kg)groups.Four groups of rats were continuously administered by 5% arabia gum 0.5ml/100g/d and 6-gingerol 5?g / 100g/ d,20?g / 100g/ d respectively in each morning for 5 weeks.Oral glucose tolerance test(OGTT)was performed at the end of fourth weekend.Rats were sacrificed after 5 week feeding.Blood samples were collected for determination of plasma concentrations of glucose,triglyceride,total cholesterol and non-esterified fatty acid.Liver and muscle were observed by HE staining and Oil Red O staining.The mRNA and protein expression were analyzed by real-time PCR and Western blot respectively.Results The results showed that co-administration of 6-gingerol(200?g /kg,once daily,by oral gavage)over 5 weeks dramatically diminished fructose-induced increases in hepatic/muscle triglyceride content and Oil Red O-stained area in rats.However,body mass of rats,fructose and chow intakes,white adipose tissue weight and metabolic parameters(plasma concentrations of glucose,insulin,triglyceride,total cholesterol and non-esterified fatty acids)were unaffected by 6-gingerol.But 6-gingerol inhibited chronic liquid fructose consumption-induced increases in plasma insulin concentrations at the baseline and during oral glucose tolerance test(OGTT),and the homeostasis model assessment of insulin resistance index.Fructose consumption induced swelling and vacuolization of hepatocytes,6-gingerol(200?g/kg)attenuated this morphologic change.Mechanistically,6-gingerol elevated peroxisome proliferator-activated receptor(PPAR)? expression at the mRNA and protein levels and increased ACOX,CPT1 mRNA expression in liver.Immunofluorescence staining and CD36 Protein expressing in gastrocnemius revealed that 6-gingerol restored fructose-stimulated sarcolemmal CD36 overexpression and decreased intracellular CD36 distribution in the muscle(P<0.05).The results of mitochondrial function in muscle showed: Fructose-fed reduced the clearance of oxygen free radicals,6-gingerol dramatically enhanced the enzyme activity of SDH and NOX(P<0.05).Conclusions 6-gingerol mitigates fructose-induced insulin resistance by stimulating peroxisome proliferator-activated receptor(PPAR)? expression at the mRNA and protein levels in the liver and modulating sarcolemmal and intracellular CD36 redistribution in the skeletal muscle,which may be related to mitochondrial function enchancement.