摘要
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 andhypoxia 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.
The increasing prevalence of obesity causes a majorinterest in white adipose tissue biology. Adipose tissuecells are surrounded by extracellular matrix proteinswhose composition and remodeling is of crucial importancefor cell function. The expansion of adipose tissue inobesity is linked to an inappropriate supply with oxygenand hypoxia development. Subsequent activation ofhypoxia inducible factor 1 （HIF-1） inhibits preadipocytedifferentiation and initiates adipose tissue fibrosis. Therebyadipose tissue growth is limited and excess triglyceridesare stored in ectopic tissues. Stressed adipocytes andhypoxia contribute to immune cell immigration andactivation which further aggravates adipose tissuefibrosis. There is substantial evidence that adipose tissuefibrosis is linked to metabolic dysfunction,both in rodentmodels and in the clinical setting. Peroxisome proliferatoractivated receptor gamma agonists and adiponectin bothreduce adipose tissue fibrosis, inflammation and insulinresistance. Current knowledge suggests that antifibroticdrugs, increasing adipose tissue oxygen supply or HIF-1antagonists will improve adipose tissue function andthereby ameliorate metabolic diseases.
基金
Supported by A grant of the German Research Foundation(BU 1141/8-1)
