Published online May 15, 2015. doi: 10.4239/wjd.v6.i4.548
Peer-review started: November 11, 2014
First decision: December 26, 2014
Revised: January 12, 2015
Accepted: February 9, 2015
Article in press: February 11, 2015
Published online: May 15, 2015
Processing time: 186 Days and 0.6 Hours
The increasing prevalence of obesity causes a major interest in white adipose tissue biology. Adipose tissue cells are surrounded by extracellular matrix proteins whose composition and remodeling is of crucial importance for cell function. The expansion of adipose tissue in obesity is linked to an inappropriate supply with oxygen and hypoxia development. Subsequent activation of hypoxia inducible factor 1 (HIF-1) inhibits preadipocyte differentiation and initiates adipose tissue fibrosis. Thereby adipose tissue growth is limited and excess triglycerides are stored in ectopic tissues. Stressed adipocytes and hypoxia contribute to immune cell immigration and activation which further aggravates adipose tissue fibrosis. There is substantial evidence that adipose tissue fibrosis is linked to metabolic dysfunction, both in rodent models and in the clinical setting. Peroxisome proliferator activated receptor gamma agonists and adiponectin both reduce adipose tissue fibrosis, inflammation and insulin resistance. Current knowledge suggests that antifibrotic drugs, increasing adipose tissue oxygen supply or HIF-1 antagonists will improve adipose tissue function and thereby ameliorate metabolic diseases.
Core tip: The close association of adipose tissue fibrosis and metabolic complications in obesity has been corroborated in rodent and human studies. Adipose tissue hypoxia initiates fibrosis which is further aggravated by inflammation. In adipose tissue preadipocytes, adipocytes and resident macrophages produce collagen showing that the fibrotic process differs from the extensively studied scar formation in the liver. Strategies to resolve fibrosis in fat tissues thereby promoting healthy adipose tissue growth are suggested to improve metabolic situation in obese patients.