The Development of Renal Injury is Accelerated in Obese Shrsp.Z-Leprfa/Izmdmcr Rats

Yasui N; Negishi H; Tsukuma R; Juman S; Miki T; Ikeda K

Abstract

The Development of Renal Injury is Accelerated in Obese Shrsp.Z-Leprfa/Izmdmcr Rats

Metabolic syndrome is a risk factor for the development of diabetes and cardiovascular disease, and was recently linked to chronic kidney disease. Several metabolic disorders similar to metabolic syndrome patients occur in SHRSP.Z-Lepfa/ IzmDmcr rats (SPZF), which have a miss-sense mutation of leptin receptor gene from the genetic background of stroke-prone spontaneously hypertensive rats (SHRSP). These characters may affect renal function. We therefore investigated the development of renal injury in SPZF. SPZF at 12 weeks of age and age-matched their lean littermates (Lean) were used for physiological, blood and urine parameters. SPZF and Lean rats were sacrificed, and epididymal, mesenteric and retroperitoneal adipose tissues, kidney, and blood were sampled. Both SHRSP.ZF and Lean had hypertension because of the genetic background of SHRSP. SHRSP.ZF showed obesity, hyperglycemia, dislipidemia, and hyperinsulinemia as well as increased urinary excretion of urinary protein, albumin and neutrophil gelatinase-associated lipocalin in SPZF than in Lean. In histological analysis, the glomerular sclerosis score was significantly higher in SPZF than in Lean. Renal transforming growth factor beta 1 (TGF-β) and TGF-β receptor mRNA expressions in SPZF were significantly higher than in Lean. Serum monocyte chemoattractant protein-1 (MCP-1) was markedly higher (p<0.01) in SPZF than in Lean. Expressions of MCP-1 mRNA in SPZF retroperitoneal adipose tissue were significantly elevated compared with Lean. Kidney MCP-1 level in SPZF was also higher than in Lean. From these results, we concluded that SPZF at 12 weeks of age developed renal injury, the mechanism of which may be associated with TGF-β and MCP-1.