Levels of adiponectin, a marker for PPAR-gamma activity, correlate with skin fibrosis in systemic sclerosis: potential utility as a biomarker?

Abstract

IntroductionProgressive fibrosis in systemic sclerosis (SSc) is linked to aberrant transforming growth factor beta (TGF-beta) signaling. Peroxisome proliferator-activated receptor gamma (PPAR-gamma) blocks fibrogenic TGF-beta responses in vitro and in vivo. Reduced expression and function of PPAR-gamma in patients with SSc may contribute to progression of fibrosis. Here we evaluated the levels of adiponectin, a sensitive and specific index of PPAR-gamma activity, as a potential fibrogenic biomarker in SSc.MethodsAdiponectin levels were determined in the sera of 129 patients with SSc and 86 healthy controls, and serial determinations were performed in 27 patients. Levels of adiponectin mRNA in skin biopsies from SSc patients were assessed in an expression profiling microarray dataset. Regulation of adiponectin gene expression in explanted human subcutaneous preadipocytes and fibroblasts was examined by real-time quantitative PCR.ResultsPatients with diffuse cutaneous SSc had reduced serum adiponectin levels. A significant inverse correlation between adiponectin levels and the modified Rodnan skin score was observed. In longitudinal studies changes in serum adiponectin levels were inversely correlated with changes in skin fibrosis. Skin biopsies from a subset of SSc patients showed reduced adiponectin mRNA expression which was inversely correlated with the skin score. An agonist ligand of PPAR-gamma potently induced adiponectin expression in explanted mesenchymal cells in vitro.ConclusionsLevels of adiponectin, reflecting PPAR-gamma activity, are correlated with skin fibrosis and might have potential utility as a biomarker in SSc.

Serum adipokines levels in patients with systemic sclerosis: A meta-analysis

“…Masui et al [12], Winsz-Szczotka et al [13] and Ozgen et al [14] have showed that serum/plasma adiponectin levels in SSc patients were significantly lower than that in normal subjects, while Lakota et al [15] and Arakawa et al [16] have showed serum/plasma adiponectin levels of SSc patients were similar to that in healthy subjects. For the circulating leptin levels in SSc patients, the inconclusive or contradictory results have also been observed.…”

Toll-Like Receptor-4 Signaling Drives Persistent Fibroblast Activation and Prevents Fibrosis Resolution in Scleroderma

“…Treatment of fibroblasts with adiponectin, an adipocyte-derived peptide that is reduced in patients with SSc, blocked TLR-dependent fibrotic responses. 58,59 Remarkably, adiponectin induces sustained upregulation of A20 in fibroblasts. Pharmacologic agents that induce A20 expression, such as vitamin E (c-tocotrienol) and adiponectin, hold promise as antifibrotic therapies by restoring endogenous A20 expression, particularly when targeted in a tissue-restricted manner, such as by topical application.…”

Propolis restored adiponectin level in type 2 diabetes through PPARγ activation

“…PPARγ binds directly to a functional PPAR-responsive element (PPRE) in adiponectin promoter, leading to enhancement of adiponectin gene transcription [17]. Indeed, adiponectin was believed to be a marker for activity of PPARγ [18].…”