Adipocyte-specific Atp7a Knockout Mice Are Resistant To Diet-induced Obesity

Adipose tissue metabolism is an important factor affecting production efficiency in husbandry production.Diets to add a certain amount of fat can improve feed efficiency,promote animal growth,and effectively promote the production of livestock.In particular,the fat of pork,intramuscular fat content and muscle fat content is closely related to the quality of pork,on the contrary,too much fat will affect the pork taste,is not conducive to the production of lean pigs.Adipose tissue is not only the energy metabolism organs,but also endocrine organs,can secrete a variety of cytokines,including adiponectin,leptin,tumor necrosis factor ? and interleukin 6,to taking the regulation of fat metabolism.Adiponectin is an insulin-sensitizing hormone that associated with insulin resistance.ATP7 A gene controls the expression of copper transporter ATP7 A,regulates intracellular and extracellular copper homeostasis,and ensures efficient transport of copper in the body and normal functions.In recent years,a small amount of papers has reported that copper played a very critical role in lipid metabolism,but the specific molecular mechanism is still unknown.In order to study the function of ATP7 A gene in mature adipocytes and the effect of copper on fat metabolism,the ATP7 A adipose tissue-specific knockout mice(KO)were successfully prepared by using the flox-cre conditional knockout system.Mice were phenotypically analyzed.The results showed that the KO mice did not show significant changes in the adipose tissue of KO mice compared with wild-type(WT)mice after 6 months of feeding.However,compared with WT,the body weight of KO mice was significantly lower(P<0.01)after 20 weeks of feeding high fat diet.MRI analysis showed a significant reduction in fat content,showing resistance to fat diet-induced obesity phenotype.However,further studies have shown that KO mice have a significantly higher liver weight than WT(P<0.05),and H & E sections showed that fatty liver is present in KO mice induced by high fat.Glucose tolerance test and insulin tolerance test showed that high fat-induced KO mice showed significant insulin resistance,significantly elevated plasma insulin levels and reduced adiponectin,further demonstrating that the mouse lipid ectopic deposition and the phenotype of insulin resistance.The WB results of subcutaneous fat showed a significant change in the expression of genes related to lipolytic metabolism(such as HSL,ATGL).This study demonstrated that ATP7 A adipose tissue-specific knockout mice showed fat ectopic deposition and insulin resistance after hyperlipidemia and found that it was resistant to obesity by promoting lipolysis.It is proved that ATP7 A regulates the metabolism of fat by adjusting the steady state of copper,which provides another new idea for further study of fat metabolism regulation.