Enhancing hepatic gluconeogenesis is one of the main modes of meeting the glucose requirement of dairy cows.This study attempted to determine whether the gluconeogenesis precursor propionate had an effect on the expre...Enhancing hepatic gluconeogenesis is one of the main modes of meeting the glucose requirement of dairy cows.This study attempted to determine whether the gluconeogenesis precursor propionate had an effect on the expression of the main genes involved in gluconeogenesis in calf hepatocytes and elucidate the associated mechanisms.Calf hepatocytes were obtained from 5 healthy calves(1 d old;30to 40 kg)and exposed to 0-,1-,2.5-,or 5-mM sodium propionate(NaP),which is known to promote the expression of genes involved in the gluconeogenesis pathway,including fructose 1,6-bisphosphatase,phosphoenolpyruvate carboxykinase,and glucose-6-phosphatase.With regard to the underlying mechanism,propionate promoted the expression of peroxisome proliferator-activated receptor gamma coactivator 1-alpha,hepatocyte nuclear factor 4,and forkhead box O1(transcription factors that regulate the expression of hepatic gluconeogenic genes)by promoting mammalian target of rapamycin complex 1(mTORC1),but inhibiting mTORC2 activity(P<0.01).We also established a model of palmitic acid(PA)-induced hepatic injury in calf hepatocytes and found that PA could inhibit the gluconeogenic capacity of calf hepatocytes by suppressing the expression of gluconeogenic genes,inhibiting m TORC1,and promoting the activity of m TORC2(P<0.01).In contrast,NaP provided protection to calf hepatocytes by counteracting the inhibitory effect of PA on the gluconeogenic capacity of calf hepatocytes(P<0.05).Collectively,these findings indicate that NaP enhances the gluconeogenic capacity of calf hepatocytes by regulating the mTOR pathway activity.Thus,in addition to improving the glucose production potential,propionate may have therapeutic potential for the treatment of hepatic injury in dairy cows.展开更多
基金supported by the National Natural Science Foundation of China(grant numbers 32070782,32072761,32100578)the Guangdong Basic and Applied Basic Research Foundation(grant number 2021A1515220036).
文摘Enhancing hepatic gluconeogenesis is one of the main modes of meeting the glucose requirement of dairy cows.This study attempted to determine whether the gluconeogenesis precursor propionate had an effect on the expression of the main genes involved in gluconeogenesis in calf hepatocytes and elucidate the associated mechanisms.Calf hepatocytes were obtained from 5 healthy calves(1 d old;30to 40 kg)and exposed to 0-,1-,2.5-,or 5-mM sodium propionate(NaP),which is known to promote the expression of genes involved in the gluconeogenesis pathway,including fructose 1,6-bisphosphatase,phosphoenolpyruvate carboxykinase,and glucose-6-phosphatase.With regard to the underlying mechanism,propionate promoted the expression of peroxisome proliferator-activated receptor gamma coactivator 1-alpha,hepatocyte nuclear factor 4,and forkhead box O1(transcription factors that regulate the expression of hepatic gluconeogenic genes)by promoting mammalian target of rapamycin complex 1(mTORC1),but inhibiting mTORC2 activity(P<0.01).We also established a model of palmitic acid(PA)-induced hepatic injury in calf hepatocytes and found that PA could inhibit the gluconeogenic capacity of calf hepatocytes by suppressing the expression of gluconeogenic genes,inhibiting m TORC1,and promoting the activity of m TORC2(P<0.01).In contrast,NaP provided protection to calf hepatocytes by counteracting the inhibitory effect of PA on the gluconeogenic capacity of calf hepatocytes(P<0.05).Collectively,these findings indicate that NaP enhances the gluconeogenic capacity of calf hepatocytes by regulating the mTOR pathway activity.Thus,in addition to improving the glucose production potential,propionate may have therapeutic potential for the treatment of hepatic injury in dairy cows.
