title: Chenodeoxycholic acid, an endogenous FXR ligand alters adipokines and reverses insulin resistance.
abstract: Adipose tissue secretes adipokines that regulate insulin sensitivity in adipocytes and other peripheral tissues critical to glucose metabolism. Insulin resistance is associated with severe alterations in adipokines characterized by release of increased pro-inflammatory cytokines and decreased anti-inflammatory cytokines from adipose tissue. The role of Farnesoid X receptor (FXR) activation on adipokines in relation to adipose tissue inflammation and insulin resistance is not completely explored. For the first time, we have evaluated the ability of Chenodeoxycholic acid (CDCA), an endogenous FXR ligand, in restoring the disturbance in adipokine secretion and insulin resistance in palmitate treated 3T3-L1 cells and adipose tissues of High fat diet (HFD) rats. CDCA suppressed several of the tested pro-inflammatory adipokines (TNF-α, MCP-1, IL-6, Chemerin, PAI, RBP4, resistin, vaspin), and enhanced the major anti-inflammatory and insulin sensitizing adipokines (adiponectin, leptin). CDCA suppressed the activation of critical inflammatory regulators such as NF-κB and IKKβ which are activated by palmitate treatment in differentiated cells and HFD in rats. We show the altered adipokines in insulin resistance, its association with inflammatory regulators, and the role of CDCA in amelioration of insulin resistance by modulation of adipokines.
authors.affiliation: Structural Biology Lab, Centre for Biomedical Research, School of Bio Sciences and Technology, VIT University, Vellore, 632 014, Tamil Nadu, India.
authors.forename: Mohamed Sham
authors.initials: MS
authors.lastname: Shihabudeen
authors.affiliation: Structural Biology Lab, Centre for Biomedical Research, School of Bio Sciences and Technology, VIT University, Vellore, 632 014, Tamil Nadu, India.
authors.forename: Debasish
authors.initials: D
authors.lastname: Roy
authors.affiliation: Structural Biology Lab, Centre for Biomedical Research, School of Bio Sciences and Technology, VIT University, Vellore, 632 014, Tamil Nadu, India.
authors.forename: Joel
authors.initials: J
authors.lastname: James
authors.affiliation: Structural Biology Lab, Centre for Biomedical Research, School of Bio Sciences and Technology, VIT University, Vellore, 632 014, Tamil Nadu, India. Electronic address: m.kavitha@vit.ac.in.
authors.forename: Kavitha
authors.initials: K
authors.lastname: Thirumurugan
mesh_terms: D041721:3T3-L1 Cells; D054392:Adipokines / Q000378:metabolism*; D000273:Adipose Tissue / Q000187:drug effects / Q000473:pathology; D000818:Animals; D002635:Chenodeoxycholic Acid / Q000378:metabolism*; D005786:Gene Expression Regulation / Q000187:drug effects; D007249:Inflammation / Q000378:metabolism; D018836:Inflammation Mediators / Q000494:pharmacology; D007333:Insulin Resistance; D008297:Male; D051379:Mice; D019308:Palmitic Acid / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D018160:Receptors, Cytoplasmic and Nuclear / Q000378:metabolism*; D000099150:Receptor, Farnesoid X-Activated
chemical_list: D054392:Adipokines; D002635:Chenodeoxycholic Acid; D018836:Inflammation Mediators; D019308:Palmitic Acid; D018160:Receptors, Cytoplasmic and Nuclear; D000099150:Receptor, Farnesoid X-Activated
keywords: Adipokines; Chenodeoxycholic acid; High fat diet; Insulin resistance; Palmitate