Intraperitoneal administration of the globular adiponectin gene ameliorates diabetic nephropathy in Wistar rats

Abstract

The present study investigated the potential effects of the long-term expression of exogenous adiponectin (ADPN) on normal and diabetic kidneys. Type 2 diabetes mellitus models were induced by high-lipid and high-sucrose feeding plus intraperitoneal injection of streptozotocin. The recombinant plasmid pIRES2-EGFP-gAd, which is able to co-express globular ADPN (gAd) and enhanced green fluorescent protein (EGFP), was intraperitoneally injected into rat models mediated by Lipofectamine. In total, 32 Wistar rats were randomly assigned into four groups: the normal control group, the diabetes group, the diabetes group treated with pIRES2-EGFP-gAd and the diabetes group treated with pIRES2-EGFP. After 12 weeks, serum biochemistry and urine albumin levels were measured. The kidneys were collected to assess the generation of reactive oxygen species (ROS) and the renal pathological changes were observed by light microcopy. The protein expression of endothelial nitric oxide synthase (eNOS), transforming growth factor-β1 (TGF-β1) and phosphorylated adenosine monophosphate-activated protein kinase (p-AMPK) were determined by an immunohistochemical staining method and western blot analysis. Intraperitoneal injection of the human gAd gene via Lipofectamine resulted in abundant ADPN protein in the kidney. In the diabetic rats, the delivery of the exogenous gAd gene ameliorated the progression of diabetic nephropathy (DN). ADPN attenuated urine albumin excretion in the diabetic rats. ADPN also mitigated glomerular mesangial expansion, reduced the generation of ROS and prevented interstitial fibrosis. In addition, the expression of gAd inhibited the renal expression of TGF-β1, promoted the protein expression of eNOS and activated the opening of the AMPK signaling pathway in the renal tissues of the diabetic rats. Despite the effects of ADPN on DN being controversial, these observations indicate that the supplementation of ADPN is beneficial in ameliorating DN in rats.

Maternal exposure to high-fat and high-fructose diet evokes hypoadiponectinemia and kidney injury in rat offspring

“…In contrast to the case of adiponectin deficiency, administration of adiponectin has been reported to improve podocyte permeability to albumin through the inhibition of NADPH oxidase activity [20]. Intraperitoneal infusion of adiponectin has also been shown to decrease renal TGF-b expression and improve mesangial expansion in the kidneys of diabetic rats [21]. Furthermore, in an obese African-American population, there was a significant and inverse correlation between plasma adiponectin concentration and UAE values [20].…”

Review: adiponectin in retinopathy

“…Serum APN levels in type 1 diabetes positively correlate with plasma total antioxidant status[70]. Increased APN levels are associated with less renal disease[71], suggesting possible protective effects of APN with respect to other type 1 diabetes complications including diabetic retinopathy. In type 2 diabetic patients, circulating APN levels are positively correlated with retinal blood flow in male patients with early-phase diabetic retinopathy, possibly through increased blood velocity and dilated vessels[5].…”

Selective Activation of AMPKβ1-Containing Isoforms Improves Kidney Function in a Rat Model of Diabetic Nephropathy

“…Multiple interventional studies in rodent models of diabetic kidney disease have suggested the potential benefits of activating AMPK for DN. Many of these studies used activators of AMPK that also have AMPK-independent activities, which could impact kidney function autonomously or nonautonomously and are limited in their capacity to activate AMPK at clinically relevant doses (Lee et al, 2007;Sharma et al, 2008;Dugan et al, 2013;Kim et al, 2013;Yuan et al, 2014). Therefore, we set out to identify novel, specific, small molecule activators of AMPK that hold the potential for clinical development as a treatment option for DN.…”