The Effect And Mechanism Of IL-6 On Visceral Fat Accumulation In Aged Mice

Background:With the acceleration of the aging process of the global population,the incidence of chronic metabolic diseases in the aging population is also increasing year by year.Among them,the abnormal accumulation of visceral fat causes the disorder of lipid metabolism and causes the occurrence of chronic metabolic diseases.Interleukin-6(IL-6)is a multifunctional factor involved in the aging process of the body and the regulation of lipid metabolism.Objective:This study investigated the effect of IL-6 on fat metabolism during aging and its mechanism.Methods:1.Aging led to slower metabolism and increased visceral fat in mice,while IL-6 gene knockout mice improved visceral fat accumulation,increased food intake,oxygen consumption and carbon dioxide production in mice,but had no significant effect on liver and subcutaneous fat.2.Observe the metabolic status of mice by metabolic cage detection,observe the morphology of fat cells by HE staining.3.Transcriptome sequencing technology was used to detect the expression of visceral fat gene.4.Expressions of visceral fat and brown fat-related genes were detected by realtime PCR and Western Blot.Results:1.Aging led to slower metabolism and increased visceral fat in mice,while IL-6 gene knockout mice improved visceral fat accumulation and increased food intake,oxygen consumption and carbon dioxide production in mice,but had no significant effect on liver and subcutaneous fat.2.Transcriptome sequencing revealed significant enrichment of the cAMP pathway in knockout mice.3.In the visceral fat of aged mice,the protein phosphorylation levels of HSL and Perilipinl decreased,while the lipolysis capacity of the aging IL-6 knockout mice increased compared with that of the aging wild-type mice.But the expression of phosphorylated CREB in visceral fat is very low.4.The expression level of p38 in visceral fat of the aging mice was not changed in the younger mice,but the phosphorylation level was significantly increased.The deletion of IL-6 inhibited the expression of p-p3 8 in the visceral adipose tissue of aging mice.5.Aging had no significant effect on phosphorylated STAT3 in visceral fat,and IL-6 knockout did not affect the change of STAT3.Phosphorylated AMPK was decreased in visceral fat of aging mice,but IL-6 knockout did not affect its expression level.6.PGC1α protein levels in visceral fat of aging mice decreased,while IL-6 knockout increased expression in visceral fat.7.In brown adipose tissue of aging mice,mRNA levels of fatty acid transporters CD36 and-oxidation-related genes MCAD and PGC1α were down-regulated,while mRNA levels of CD36,MCAD and CYTC were up-regulated by IL-6 knockout.In addition,IL-6 knockout up-regulated the MCAD protein level in the visceral adipose tissue of old mice,but it had no effect on UCP1 or PGC1α.Conclusion:IL-6 knockout can improve the age-affected visceral adipose tissue gain and weight gain,and can partially restore the metabolism level of body.IL-6 knockout can improve the accumulation of age-affected visceral fat through the cAMP/PKA/HSL pathway.The main expression was the increase of catecholamineinduced lipoly sis(HSL)in visceral fat after IL-6 knockout,and the expression of p3 8 MAPK in senescent visceral fat was inhibited by IL-6 knockout.IL-6 knockout can promote the expression of PGCla in visceral adipose tissue.Aging leads to decreased fatty acid intake and metabolic capacity of brown adipose tissue,while IL-6 knockout can partially restore the metabolic function of brown adipose tissue and promote the intake and oxidative decomposition of fatty acids.