Abstract: This study aims to investigate the effect of ursolic acid (UA) on glycolipid metabolism disorder and hepatic autophagy in naturally ageing rats.Twenty-five male aging rats were divided randomly into three groups:the natural aging rat group (Aging,n=9),the aging rats supplemented with ursolic acid at 10 mg/kg (UA-L,n=8) and 50 mg/kg (UA-H,n=8) for 7 weeks.Eight young rats were randomly selected as the young normal group (Young,n=8).Enzymatical method and ELISA were used for the examination of plasma glucose,triglycerides,insulin concentrations and HOMA-IR index was calculated;Liver triglycerides were measured by enzymatical method;Liver lipid deposition was observed by Oil Red "O" staining;The autophagy-related proteins and mitochondrial quality proteins were analysed by Western blot.Results showed that treatment with UA (50 mg/kg,once daily,by oral gavage) could attenuate age-associated high plasma TG and insulin concentration under fasting conditions as well as suppress the increase in the HOMA-IR index,which suggests there is an improvement of systemic insulin sensitivity.Moreover,liver weight and hepatic triglyceride content were also decreased.Attenuation of the increased Oil Red O staining area was evident on histological examination of liver in UA (50 mg/kg)-treated rats.Importantly,UA (50 mg/kg) administration reversed the decreased expressions of autophagy-related proteins LC3B/3A,Beclin1 and mitochondrial quality proteins PGC-1α,Drp1 in aging rats,although P62,Pink1 remained unchanged.The results suggest that UA may attenuate systematic insulin resistance and hepatic lipid deposition,enhance hepatic autophagy,improve mitochondrial quality in aging rats.

Key words: ursolic acid, autophagy, glycolipid metabolism disorder, mitochondrial quality, aging rats