The Relationship Between The Expression Of 11?-HSD1 In Perirenal Adipose Tissue And Inflammation With Sarcopenia

Objectives.As a core component of elderly weakness,sarcopenia leads to physical disability,multiple diseases,and even death.Therefore,sarcopenia and its complications have captured wide attention.Longitudinal studies have shown that with aging most individuals tend to develop a chronic low-grade proinflammatory state,and that such a state is a strong risk factor for sarcopenia.Recently,a series of investigations have demonstrated that adipose tissue inflammation plays an important role in modifying the inflammatory state in aging.Numerous studies have showed that adipose tissue,an important endocrine tissue,secretes large amounts of cytokines,triggering and promoting systemic inflammation.Our previous study investigated that11?-hydroxysteroid dehydrogenase type 1(11?-HSD1),an amplifier of local glucocorticoid activity,led to a significant inhibition of the inflammatory state in adipocytes,indicating that 11?-HSD1 acts as a vital regulator that controls the adipose tissue inflammation.Furthermore,we observed a striking improvement of cardiac remolding and attenuation of cardiac hypertrophy in BVT.2733(a selective inhibitor of 11?-HSD1)-treated rats.Moreover,osteoblast function also regulated by11?-HSD1 which is a underlying mechanism of osteoporosis.Therefore,11?-HSD1 might play a key role in aging via controlling the inflammatory state in adipose tissue.In this proposal,we hypothesize that 11?-HSD1,regulating the fat inflammation,plays key role in sarcopenia.Methods.The patients who underwent kidney surgery were screened to document general information including age,gender,body mass index(BMI)and to test biochemical profile including high-sensitivity high sensitive C-reactive protein(hs CRP),alanine aminotransferase(ALT),aspartate aminotransferase(AST),blood urea nitrogen(BUN),creatinine(Cr),uric acid,total cholesterol(TC),triglyceride(TG),high density lipoprotein cholesterol(HDL-C)and low density lipoprotein cholesterol(HDL-C).Sarcopenia was diagnosed according to the consensus of the2 nd expert meeting 2018 of the European Working Group on Sarcopenia in Older People(EWGSOP).Perirenal fat,from kidney inferior pole,was collected for testing relative m RNA expression levels of adipokines,inflammatory factors,and aging factors.Results.The data showed that serum hs C-reactive protein(hs CRP)correlated with grip strength.The grip strength value decreased with the increase of serum hs CRP.Serum hs CRP increased with the increase of IL-8 and MCP-1 m RNA expression in adipose tissue.Furthermore,11?-HSD1 m RNA expression of adipose tissue was significantly correlated with the gene expressions of adipokines(adiponection,leptin,resistin),inflammatory factors and the level of serum hs CRP,and also markedly correlated with grip strength,muscle mass and walk speed.In addition,the m RNA expression of cellular senescence marker protein(p16Ink4a,p21Cip1)were strikingly increased with the increase of the expression of 11?-HSD1.Conclusions.11?-HSD1 is an important regulator for adipokines(adiponection,leptin,resistin),inflammatory factors and cellular senescence markers in adipose tissue.The adipose tissue inflammation,which may lead to systemic inflammation,is significantly associated with the decrease of grip strength.Therefore,11?-HSD1,regulating the fat inflammation,might play key roles in sarcopenia.