Sterol regulatory element-binding factor-1 and-2(SREBF1 and SREBF2)are important transcription factors involved in the regulating lipid homeostasis.Based on the essential role of SREBF1 and SREBF2,we measured the mRNA...Sterol regulatory element-binding factor-1 and-2(SREBF1 and SREBF2)are important transcription factors involved in the regulating lipid homeostasis.Based on the essential role of SREBF1 and SREBF2,we measured the mRNA expression levels of the two genes in six various tissues at different growth points.Our results showed that the SREBF1 and SREBF2 were expressed in all six tissues examined in Erlang mountainous chicken(SD02)at 42 d,and were expressed abundantly in the uropygial gland and liver,with relatively lowest levels of expression in the abdominal fat,sebum cutaneum and leg muscle.The expression ratio of SREBF1 and SREBF2 in breast muscle,leg muscle,sebum cutaneum and uropygial gland exhibited a"decline-rise"trend.However,in liver,the expression ratio of these two genes exhibited a"decline-rise-decline"trend.Meanwhile,the expression level of SREBF1 gene of all tissues was lower than that of SREBF2 except for uropygial gland.The findings will provide important references for further function investigation of the two genes involved in fat deposition in chickens.展开更多
Previous studies have indicated an association of fat mass and obesity-associated(FTO)with nonalcoholic fatty liver disease(NAFLD),the most common chronic liver disease worldwide.This study aimed to decipher the compl...Previous studies have indicated an association of fat mass and obesity-associated(FTO)with nonalcoholic fatty liver disease(NAFLD),the most common chronic liver disease worldwide.This study aimed to decipher the complex role of FTO in hepatic lipid metabolism.We found that a decrease in N^(6)-methyladenosine(m^(6)A)RNA methylation in the liver of mice fed with a high-fat diet(HFD)was accompanied by an increase in FTO expression.Overexpression of FTO in the liver promoted triglyceride accumulation by upregulating the expression of lipogenic genes.Mechanistical studies revealed that FTO could stabilize the mRNAs of sterol regulatory element binding transcription factor 1(SREBF1)and carbohydrate responsive element binding protein(ChREBP),two master lipogenic transcription factors,by demethylating m^(6)A sites.Knockdown ofeither SREBF1 or ChREBP attenuated the lipogenic effect of FTO,suggesting that they are bona fide effectors for FTO in regulating lipogenesis.Insulin could stimulate FTO transcription through a mechanism involving the action of intranuclear insulin receptor beta,while knockdown of FTO abrogated the lipogenic effect of insulin.Inhibition ofFTo by entacapone decreased the expression of SREBF1,ChREBP,and downstream lipogenic genes,ameliorating liver steatosis in HFD-fed mice.Thus,our study established a critical role of FTO in both the insulin-regulated hepatic lipogenesis and the pathogenesis of NAFLD and provided a potential strategyfor treating NAFLD.展开更多
基金Key Technology Support Program of Sichuan Province(2018NZDZX0004,2016NZ0104)Financial Project of Sichuan Province(SASA2020CZYX002)。
文摘Sterol regulatory element-binding factor-1 and-2(SREBF1 and SREBF2)are important transcription factors involved in the regulating lipid homeostasis.Based on the essential role of SREBF1 and SREBF2,we measured the mRNA expression levels of the two genes in six various tissues at different growth points.Our results showed that the SREBF1 and SREBF2 were expressed in all six tissues examined in Erlang mountainous chicken(SD02)at 42 d,and were expressed abundantly in the uropygial gland and liver,with relatively lowest levels of expression in the abdominal fat,sebum cutaneum and leg muscle.The expression ratio of SREBF1 and SREBF2 in breast muscle,leg muscle,sebum cutaneum and uropygial gland exhibited a"decline-rise"trend.However,in liver,the expression ratio of these two genes exhibited a"decline-rise-decline"trend.Meanwhile,the expression level of SREBF1 gene of all tissues was lower than that of SREBF2 except for uropygial gland.The findings will provide important references for further function investigation of the two genes involved in fat deposition in chickens.
基金This work was supported by the Chinese Ministry of Science and Technology(2021YFA1100500)the National Natural Science Foundation of China(NSFC,91957205,82070821,and 82000805)+4 种基金Youth Innovation Promotion Association,Chinese Academy of Sciences(2021261)Pujiang Talent Program from the Science and Technology Commission of Shanghai Municipality(21PJ1416100)Young Elite Scientists Sponsorship Program by China Association for Science and Technology(2020QNRC001)the Collaborative Innovation Center of Food Safety and Quality Control in Jiangsu Province,Jiangnan University(2022-3-1)NHC Key Laboratory of Food Safety Risk Assessment(2020K02).
文摘Previous studies have indicated an association of fat mass and obesity-associated(FTO)with nonalcoholic fatty liver disease(NAFLD),the most common chronic liver disease worldwide.This study aimed to decipher the complex role of FTO in hepatic lipid metabolism.We found that a decrease in N^(6)-methyladenosine(m^(6)A)RNA methylation in the liver of mice fed with a high-fat diet(HFD)was accompanied by an increase in FTO expression.Overexpression of FTO in the liver promoted triglyceride accumulation by upregulating the expression of lipogenic genes.Mechanistical studies revealed that FTO could stabilize the mRNAs of sterol regulatory element binding transcription factor 1(SREBF1)and carbohydrate responsive element binding protein(ChREBP),two master lipogenic transcription factors,by demethylating m^(6)A sites.Knockdown ofeither SREBF1 or ChREBP attenuated the lipogenic effect of FTO,suggesting that they are bona fide effectors for FTO in regulating lipogenesis.Insulin could stimulate FTO transcription through a mechanism involving the action of intranuclear insulin receptor beta,while knockdown of FTO abrogated the lipogenic effect of insulin.Inhibition ofFTo by entacapone decreased the expression of SREBF1,ChREBP,and downstream lipogenic genes,ameliorating liver steatosis in HFD-fed mice.Thus,our study established a critical role of FTO in both the insulin-regulated hepatic lipogenesis and the pathogenesis of NAFLD and provided a potential strategyfor treating NAFLD.
