The Expression Of LZP In Mouse Models Of Obesity And Effects Of LZP On Hepatic Glucose And Lipid Metabolism

Objective: This study is aimed to explore the expression of liver-specific ZP domaincontaining protein(LZP)in mice,demonstrate the influence of LZP on hepatic glucose and lipid metabolism of obese mice and db/db mice,and discuss the underlying mechanism.Methods: C57BL/6J mice and ob/ob mice were both fed with high fat diet(HFD).The metabolic makers were monitored during the experiment,and the expression of LZP in liver was detected by RT-PCR and Western blot.HFD induced-obese mice(C57BL/6J)and db/db mice were injected with different LZP virus into tail vein.IPGTT and IPITT were operated with the mice,and some liver tissues were left for histological examination,the others were collected to test triglyceride(TG)content and detect the expression of gluconeogenesis by Western blot.Primary mouse hepatocytes were infected with LZP or GPF adenovirus,and then glucose production assay was operated and the level of cellular TG from hepatocytes treated with or without oleic acid(OA)was measured,respectively.Results:(1)LZP was mainly found in liver in mice.(2)Compared with chow diet group,the group treated with HFD had increased body mass and total fat mass(both P(27)0.05),higher blood glucose(P(27)0.05),increased liver mass(P(27)0.001)and more serious hepatic steatosis,while both the gene and protein expression of LZP in liver were reduced(both P(27)0.05).(3)The expressions of LZP in m RNA and protein level in ob/ob mice were decreased compared with wild type littermates(both P(27)0.05).(4)Compared with Ad-GFP group,the DIO mice injected with LZP adenovirus had improved glucose tolerance,insulin sensitivity(both P(27)0.01)and decreased expression of phosphoenolpyruvate carboxykinase and glucose-6-phosphatase.Meanwhile,LZP could ameliorate hepatic steatosis and lessen the hepatic TG content(P(27)0.01).(5)Compared with AAV8-GFP group,the db/db mice injected with LZP adeno-associated virus showed similar body mass and blood glucose,insulin sensitivity,serum TG concentration,hepatic TG content and the extent of hepatic steatosis(P(29)0.05).(6)The glucose productions in media were comparable between LZP adenovirus infected-and GFP adenovirus infected-primary mouse hepatocytes(P(29)0.05)while the overexpression of LZP could decrease the cellular TG content in primary mouse hepatocytes treated with OA(P(27)0.05).Conclusions: LZP was mainly expressed in liver,while mouse models of obesity displayed decreased expression of LZP.LZP could ameliorate glucolipid metabolism in obese mice but not in diabetes mice,and mediate hepatic glucose metabolism indirectly by having a direct effect on lipid metabolism.