Fibrosis in adipose tissue is correlated to liver injury in NAFLD

Background and Aims: Fibrosis occurs in different organs and is associated with damage. In non-alcoholic fatty liver disease (NAFLD), liver fibrosis is also a sign for progression. Adipose tissue seems to play an important role in the progression of NAFLD, but the contribution of adipose tissue fibrosis is unclear. The aim of our study was: (i) to check if adipose tissue in obesity exhibits fibrosis, (ii) if fibrosis in adipose tissue correlates with liver damage and fibrosis and (iii) autophagy in adipose tissue is associated with fibrosis in adipose tissue. Methods: Blood, visceral adipose and liver tissue samples were obtained from 62 (mean age: 43+/-10 y. w:45/m:17) morbidly obese patients undergoing bariatric surgery. Fibrosis was assessed by Sirius Red staining in adipose and liver tissue. mRNA expression of genes related to fibrosis (collagen) and autophagy (ATG5, LC3, Beclin) were measured in adipose and liver tissue by qrt-PCR. ATG 5 staining in adipose tissue was performed by immunohistochemistry and quantitatively analyzed. Blood samples were analyzed for routine parameters and surrogate markers of apoptosis and cell death (M30, M65) by ELISA. Results: Increased fibrosis was observed by Sirius red and collagen expression was significantly upregulated (p < 0.0001) in adipose tissue of morbidly obese patients compared to controls. mRNA levels of LC3 and Beclin were significantly increased in adipose tissue of obese patients compared to controls (LC3 p < 0.02; Beclin p < 0.05). In addition the amount of ATG5-positive cells in adipose tissue was significantly correlated with fibrosis in adipose tissue. Significant correlations were also found between adipose tissue fibrosis and serum M30 as well as expression of autophagy related genes in adipose tissue. Autophagy related gene expression in liver and adipose tissue was also correlated. Conclusions: Morbid obesity leads to fibrosis in adipose tissue, which is associated to elevated expression of autophagy related genes. Moreover, autophagy in adipose tissue and liver tissue are correlated, implicating a possible common signalling axis leading to increased autophagic processes in different tissues. The underlying mechanisms need further characterization.