Effect And Preliminary Mechanism Of Glycometabolism-unrelated HAART Regimen On Lipid Metabolism In Northern Pig-tailed Macaques Infected With SIVmac239

Objective: Highly active antiretroviral treatment(HAART)for HIV infection is regarded to induce metabolic disorder,including glycometabolism and lipid metabolism.However,HAART-induced glycometabolism can indirectly affect lipid metabolism by different ways.Therefore,this study used the northern pig-tailed macaques AIDS model as the research object,and according to the first-line treatment of AIDS recommended by the World Health Organization(WHO)and without side effects on glucose metabolism to truly reflect the effect of HAART on lipid metabolism and to explore its mechanism initially.Methods: According to the first-line treatment of AIDS recommended by the World Health Organization(WHO),and consulting the literature,three drugs that without side effects on glycometabolism were selected,namely tenofovir(PMPA),enthractabine(FTC),and latiravir(RAL),referred to as PFR treatment.This study was divided into three stages: pre-infection,post-infection and HAART.The plasma levels of total cholesterol(TC),triglyceride(TG),low-density lipoprotein cholesterol(LDL-C)and high-density lipoprotein cholesterol(HDL-C)were measured by Cobas 8000 automatic biochemical immunoassay to study the effect of PFR on the whole body lipid level.The thickness of abdominal subcutaneous adipose tissue was measured by B-mode ultrasound,and the morphological changes of subcutaneous adipose tissue were detected by hematoxylin-eosin(HE)staining to study the effect of PFR treatment on local lipid metabolism.And the plasma levels of inflammatory factors and adipocytokines were detected by enzyme-linked immunosorbent assay(ELISA)to study the systemic mechanism of abnormal lipid metabolism induced by PFR treatment.Inflammatory factors,adipocytokines and adipocyte metabolic genes in local adipose tissue were detected by real-time quantitative polymerase chain reaction(q RT-PCR)to study the local mechanism of lipid metabolism disorders caused by PFR treatment.Results: After PFR treatment,SIVmac239 infected pig-tailed macaques showed obvious dyslipidemia,which was manifested by the decrease of TC,TG,LDL-C and HDL-C,and severe trophy in subcutaneous adipose,which showed that the thickness of adipose layer and the diameter of adipocytes were decreased,which was consistent with the clinical symptoms of HIV infected patients.The results of the mechanism suggest that PFR treatment can aggravate systemic inflammatory response and cause disorders in the secretion of adipocytokines such as leptin and adiponectin.In contrast,PFR treatment did not cause significant changes in the immune microenvironment and lipid metabolism genes of local adipose tissue.Moreover,after treatment,the viral load in plasma of pig-tailed macaques decreased to below the detection line,but there was no significant difference in viral load in adipose tissue compared with pre-infection.Conclusion: HAART can directly cause dyslipidemia and fat malnutrition,including TC,TG,HDL-C,LDL-C decrease and subcutaneous fat lipoatrophy.The main cause of abnormal lipid metabolism may be systemic persistent inflammatory response and abnormal levels of adipocytokines.In addition,adipose tissue is an important viral reservoir after HAART.