The Study Of Epinephrine On The Role Of Alpha-ketoglutaric Acid Promoting Lipolysis

?-ketoglutarate acid?AKG?,the key intermediate products in TCA cycle and the metabolism of glutamate acid?Glu?,play a crucial role in protein synthesis,bone formation,Anti-aging and cancer prevention.But,the effect of AKG on animal adipose metabolism is still unknown.To investigate the effect and mechanism of AKG on adipose deposition,C57/BL6J mice and adrenal medulla cell were used.First,2%AKG was used to feed mice by supplementing into drinking water to investigate the effect of high fat diet induced obesity.The results suggested that 2%AKG significantly decreased adipose tissue weight and adipocyte size?P<0.05?.And lipolysis related protein?p-HSL,ATGL?expression was significantly increased by 2%AKG adding?P<0.05?.But,no significantly difference was observed in the expression of adipose synthesis related gene?P>0.05?.Besides,2%AKG remarkably increased energy expenditure of mice?P<0.05?and the UCP1 expression of brown adipose tissue?P<0.05?.Furthermore,2%AKG significantly increased serum epinephrine level?P<0.05?,but not the norepinephrine and thyroid hormone?P>0.05?.Then,in order to further investigate the AKG-Induced lipolysis,we also used adrenal medulla cell,which was treated with different concentration AKG.The result showed that 2mM AKG significantly promoted the release of[Ca²⁺]_i and epinephrine dose dependently in adrenal medulla cell.Moreover,our in vitro experiment showed that 2mM AKG significantly increased the release of epinephrine after 30min treatment.Finally,no obviously difference of mice respiratory quotient rate?RER?and energy expenditure was observed when inhibited epinephrine receptor?ADRB3?.Meanwhile,adrenalectomy reversed the effect of AKG on adipose metabolism.Above all,the result of adrenal medulla cell showed that AKG promoted the release of epinephrine directly.our in vivo result suggested that AKG enhanced the metabolism and decreased adipose deposition through stimulating epinephrine release,which had a positive influence in revealing the mechanism that metabolism intermediate products regulate endocrine via negative feedback.