6-Gingerol Ameliorates Age-associated Insulin Resistance In Skeletal Muscle

Purpose To investigate the actions of 6-gingerol ameliorates age-associated insulin resistance and to explore the possible mechanisms.Experimental approach Twenty-seven ageing rats were divided randomly into three groups(n=9 per group): the natural ageing rat group(Aged),the ageing rats supplemented with 6-gingerol at 0.05 mg/kg(G-L)and 0.2 mg/kg(G-H).Six young rats were randomly selected as the young normal group(NC,n=6)that did not receive treatment.At the end of week 7,blood samples were collected to measure triglycerides,total cholesterol and glucose levels by enzymatical method after an overnight fast.Plasma insulin and adiponectin levels were determinated by Elisa.Oil red O staining was used to observe the degree of fat deposition,and triglycerides level was measured by enzymatical method in muscle tissue.Immunohistochemistry was used to observe fibre type and cross-sectional area.Transmission electron microscopy was used to observe morphological changes of mitochondria in muscle fibre.Function changes of mitochondria was measured by Elisa and enzymatical methods in muscle.The protein and gene expression were detected by Western blot and Real-time PCR.Key results Treatment with 6-gingerol(0.2 mg/kg,once daily,by oral gavage)could attenuate age-associated high plasma TG,glucose and insulin concentration under fasting conditions as well as suppress the increase in the HOMA-IR index in skeletal muscle of ageing rats,which suggests there is an improvement of systemic and muscular insulin sensitivity.Accompanying these changes,treatment with 6-gingerol attenuated excessive triglyceride accumulation,repaired mitochondrial dysfunctional structures and increased mitochondrial metabolic capacity(i.e.,levels of CS,SDH,NADH and COX-IV)and mitochondrial function(ATP production)as well as promoted a transition from a fast-to slow-fibre type and muscle oxidative metabolism in the gastrocnemius of ageing rats.More importantly,6-gingerol increased not only the plasma adiponectin concentration but also muscular AdipoR1 activity and activated downstream AMPK phosphorylation as well as upregulated PGC-1?.Conclusions In conclusion,oral 6-gingerol may improve ectopic lipid accumulation,mitochondrial dysfunction and insulin resistance.These effects rely,at least in part,on the elevated plasma adiponectin concentration and the muscle AdipoR1 level to dually activate the AMPK-PGC-1? signalling pathway.