Growth Hormone as a Model for Reversible Activation of Adipose Tissue Fibrosis

Background: Adipose tissue fibrosis denotes excessive pathological accumulation of extracellular matrix (ECM) in adipose tissue and is a marker of dysfunction. Growth hormone (GH) activates adipose tissue lipolysis and stimulates collagen synthesis in lean tissues. Intriguingly, we have novel pilot data to suggest that GH excess (acromegaly) also induces reversible fibrosis in vivo and potently activates the expression of fibroblast activation protein alpha (FAPα). Hypothesis: GH induces adipose tissue fibrosis by increased FAPα expression together with proliferation and fibrogenic differentiation of fibro-adipogenic progenitor (FAP) cells. Aim: To unravel the mechanisms underlying GH-induced adipose tissue fibrosis with emphasis on FAPα expression and proliferation of FAP cells. Subjects and methods: In a single blinded, randomized, double-dummy crossover design, 10 adult, moderately overweight individuals will be subjected to one week of GH and GH receptor blockade (Pegvisomant). We will use single-cell technologies, fluorescence-activated cell sorting (FACS), RNA sequencing, and cell culture studies on adipose tissue samples, combined with in vivo assessment of adipose tissue turnover and metabolism. Perspectives: Understanding fibrosis formation in human models may identify new targets for treatment of obesity-associated disorders.