The Novel Adipokine C1q/TNF-related Protein-3 is Expressed in Human Adipocytes and Regulated by Metabolic and Infection-related Parameters

Abstract

BACKGROUND: The growing family of C1Q/TNF-related proteins is characterized by structural homologies to the anti-inflammatory adipokine adiponectin. CTRP-3 was recently reported to function as an anti-inflammatory LPS-antagonist in vitro. MATERIAL AND METHODS: Human subcutaneous and visceral adipocytes and murine 3T3-L1 adipocytes were used for analysis of CTRP-3 expression and function. Western blot analysis of CTRP-3, siRNA mediated knockdown of CTRP-3, Oil red O staining, assessment of basal and epinephrine-induced lipolysis, ELISA-based measurements of supernatant chemokines, recombinant CTRP-3 protein expression, and Staphylococcus aureus (S. aureus) infection assays were used. RESULTS: CTRP-3 is expressed in subcutaneous and visceral adipocytes. CTRP-3 is positively regulated by insulin, whereas chronic LPS-exposure inhibits terminal adipocyte differentiation and CTRP-3 expression. Intracellular infection of adipocytes by S. aureus also decreases CTRP-3 expression. As demonstrated by siRNA-mediated cellular knockdown of CTRP-3 in adipocytes, CTRP-3 regulates resistin secretion and lipolysis. CONCLUSION: CTRP-3 is expressed in human adipocytes and plays an important role in adipocyte physiology such as lipolysis and adipokine secretion. Both, metabolic factors and infection/inflammation-related factors regulate CTRP-3 expression.