Pigment epithelium-derived factor improves metabolic derangements and ameliorates dysregulation of adipocytokines in obese type 2 diabetic rats.

ABSTRACT

Oxidative stress and inflammation in the adipose tissues contribute to the metabolic syndrome. Pigment epithelium-derived factor (PEDF) inhibits vascular inflammation through its anti-oxidative properties. However, it remains unclear whether PEDF could suppress adipocyte inflammation. We investigated the effects of long-term administration or suppression of PEDF on adipocyte inflammation and metabolic derangements in Otsuka Long-Evans Tokushima Fatty (OLETF) rats, an animal model of type 2 diabetes with insulin resistance. Circulating and adipose tissue PEDF levels were increased as OLETF rats became more obese and insulin resistant. Long-term administration of PEDF improves metabolic parameters, ameliorates dysregulation of adipocytokines, and suppresses NADPH oxidase-induced oxidative stress and macrophage infiltration in the adipose tissues of OLETF rats, whereas these variables are exacerbated by the knockdown of PEDF by administering siRNAs. Our study suggests that PEDF could improve metabolic derangements by suppressing the inflammatory and oxidative reactions in adipose tissues of OLETF rats. PEDF levels may be elevated as a countersystem against obesity-related metabolic derangements.