Plasminogen activator inhibitor-1 deficiency ameliorates insulin resistance and hyperlipidemia but not bone loss in obese female mice

Abstract

We previously demonstrated that plasminogen activator inhibitor-1 (PAI-1), an inhibitor of fibrinolysis,is involved in type 1 diabetic bone loss in female mice. PAI-1 is well known as an adipogenicfactor induced by obesity. We therefore examined the effects of PAI-1 deficiency on bone andglucose and lipid metabolism in high-fat and high-sucrose diet (HF/HSD)-induced obese femalemice. Female wild-type (WT) and PAI-1-deficient mice were fed with HF/HSD or normal diet for 20weeks from 10 weeks of age. HF/HSD increased the levels of plasma PAI-1 in WT mice. PAI-1deficiency suppressed the levels of blood glucose, plasma insulin, and total cholesterol elevated byobesity. Moreover, PAI-1 deficiency improved glucose intolerance and insulin resistance inducedby obesity. Bone mineral density (BMD) at trabecular bone as well as the levels of osterix, alkalinephosphatase, and receptor activator of nuclear factor αB ligand mRNA in tibia were decreased byHF/HSD in WT mice, and those changes by HF/HSD were not affected by PAI-1 deficiency. HF/HSDincreased the levels of plasma TNF-αin bothWTand PAI-1-deficient mice, and the levels of plasmaTNF-αwere negatively correlated with trabecular BMD in tibia of female mice. In conclusion, werevealed that PAI-1 deficiency does not affect the trabecular bone loss induced by obesity despitethe amelioration of insulin resistance and hyperlipidemia in female mice. Our data suggest that thechanges ofBMDand bone metabolism by obesity might be independent of PAI-1as well as glucoseand lipid metabolism. © 2014 by the Endocrine Society.