Serum vaspin levels were related to insulin resistance, and higher levels of serum vaspin in 7% of the Japanese population are closely linked to minor allele sequence (A) of rs77060950.

Osteopontin is a proinflammatory cytokine and monocyte chemoattractant implicated in the pathogenesis of diabetic nephropathy. Synthetic agonists for liver X receptors (LXRs) suppress the expression of proinflammatory genes, including osteopontin, but whether LXR activation modulates diabetic nephropathy is unknown. We administered the LXR agonist T0901317 to mice with streptozotocin-induced diabetes and evaluated its effects on diabetic nephropathy. The LXR agonist decreased urinary albumin excretion without altering blood glucose levels and substantially attenuated macrophage infiltration, mesangial matrix accumulation, and interstitial fibrosis. LXR activation suppressed the gene expression of inflammatory mediators, including osteopontin, in the kidney cortex. In vitro, LXR activation suppressed osteopontin expression in proximal tubular epithelial cells by inhibiting AP-1-dependent transcriptional activation of the osteopontin promoter. Taken together, these results suggest that inhibition of renal osteopontin by LXR agonists may have therapeutic potential for diabetic nephropathy.

OBJECTIVEActivation of the nuclear hormone receptor peroxisome proliferator–activated receptor (PPAR)-δ has been shown to improve insulin resistance, adiposity, and plasma HDL levels. Several studies have reported that activation of PPARδ is atheroprotective; however, the role of PPARδ in renal function remains unclear. Here, we report the renoprotective effects of PPARδ activation in a model of streptozotocin-induced diabetic nephropathy.RESEARCH DESIGN AND METHODSEight-week-old male C57BL/6 mice were divided into three groups: 1) nondiabetic control mice, 2) diabetic mice, and 3) diabetic mice treated with the PPARδ agonist GW0742 (1 mg/kg/day). GW0742 was administered by gavage for 8 weeks after inducing diabetes.RESULTSGW0742 decreased urinary albumin excretion without altering blood glucose levels. Macrophage infiltration, mesangial matrix accumulation, and type IV collagen deposition were substantially attenuated by GW0742. The gene expression of inflammatory mediators in the kidney cortex, such as monocyte chemoattractant protein-1 (MCP-1) and osteopontin (OPN), was also suppressed. In vitro studies demonstrated that PPARδ activation increased the expression of anti-inflammatory corepressor B-cell lymphoma-6, which subsequently suppressed MCP-1 and OPN expression.CONCLUSIONSThese findings uncover a previously unrecognized mechanism for the renoprotective effects of PPARδ agonists and support the concept that PPARδ agonists may offer a novel therapeutic approach for the treatment of diabetic nephropathy.

No abstract

No abstract