Study Of The Effect And Mechanism Of Telomerase RNA Component Gene TERC In Nonalcoholic Fatty Liver Disease

AIM:Nonalcoholic fatty liver disease (NAFLD) is a common clinical chronic liver disease, and its pathogenesis is not fully clear. Studies have found that aging is closely related to the occurrence and development of NAFLD, and the telomerase RNA component gene TERC plays an important role in the occurrence of aging. However, whether TERC participates in the development of NAFLD and its exact molecular mechanisms have not been reported. This study aims to explore the effects of telomerase RNA gene TERC in the development of NAFLD and the possible molecular mechanism.METHOD:Methionine choline deficiency (MCD) diet was used for the second generation of telomerase knockout mice (G2 TERC-/-) and wild type mice. On this basis, we used molecular biology methods such as hematoxylin-eosin (HE) staining, liver tissue triglyceride content determination and quantitative PCR to explore the role and molecular mechanism of telomerase RNA gene TERC in NAFLD.RESULTS:(1) NAFLD animal model was successfully constructed by MCD diet; (2) G2 TERC-/-mice group significantly increased hepatic fat accumulation induced by MCD-diet. Moreover hepatic triglyceride contents in G2 TERC-/-mice group were higher than that in WT mice group (172.5μg/mg vs 150μg/mg, P=0.018); (3) The expression of fatty acid synthase (FAS) was higher in G2 TERC-/-mice group than that in wild type mice group (P=0.026), which further caused increase of lipid synthesis; (4) The expression of peroxisome proliferator-activated receptor a (PPARa) decreased in G2 TERC-/-mice group versus that in wild type mice group (P=0.050), which further caused fatty acids beta oxidative damage.CONCLUSIONS:(1) TERC was involved in the development of NAFLD; (2) TERC knockout mice increased MCD diet-induced hepatic steatosis by up-regulating the expression of FAS and down-regulating the expression of PPARa.