Pigment Epithelium–Derived Factor Improves Metabolic Derangements and Ameliorates Dysregulation of Adipocytokines in Obese Type 2 Diabetic Rats

Oxidative stress and inflammation in the adipose tissuescontribute to the metabolic syndrome. Pigment epithelium–derived factor ( PEDF) inhibits vascular inflammation through its anti-oxidative properties. However, it remains unclear whether PEDFcould suppress adipocyte inflammation. We investigated the effects of long-term administration or suppression of PEDFon 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 PEDFlevels were increased as OLETF rats became more obese and insulin resistant. Long-term administration of PEDFimproves metabolic parameters, ameliorates dysregulation of adipocytokines, and suppresses NADPH oxidase-induced oxidative stress and macrophage infiltration in the adipose tissuesof OLETF rats, whereas these variables are exacerbated by the knockdown of PEDFby administering siRNAs. Our study suggests that PEDFcould improve metabolic derangements by suppressing the inflammatory and oxidative reactions in adipose tissuesof OLETF rats. PEDFlevels may be elevated as a countersystem against obesity-related metabolic derangements.