Abstract
BackgroundHyperlipidemia is thought to be a major risk factor for the progression of renal diseases in diabetes. Recent studies have shown that lipid profiles are commonly abnormal early on type 2 diabetes mellitus (T2DM) with diabetic nephropathy. However, the early effects of triglyceride and cholesterol abnormalities on renal injury in type 1 diabetes mellitus (T1DM) are not fully understood and require reliable animal models for exploration of the underlying mechanisms. Hamster models are important tools for studying lipid metabolism because of their similarity to humans in terms of lipid utilization and high susceptibility to dietary cholesterol and fat.MethodsTwenty-four male Golden Syrian hamsters (100–110 g) were rendered diabetes by intraperitoneal injections of streptozotocin (STZ) on consecutive 3 days at dose of 30 mg/kg, Ten days after STZ injections, hamsters with a plasma Glu concentration more than 12 mmol/L were selected as insulin deficient ones and divided into four groups (D-C, D-HF, D-HC, and D-HFHC), and fed with commercially available standard rodent chow, high-fat diet, high-cholesterol diet, high-fat and cholesterol diet respectively, for a period of four weeks.ResultsAfter an induction phase, a stable model of renal injury was established with the aspects of early T1DM kidney disease, These aspects were severe hypertriglyceridemia, hypercholesterolemia, proteinuria with mesangial matrix accumulation, upgraded creatinine clearance, significant cholesterol and triglyceride deposition, and increasing glomerular surface area, thickness of basement membrane and mesangial expansion. The mRNA levels of sterol regulatory element binding protein-1c, transforming growth factors-β, plasminogen activator inhibitor-1, tumor necrosis factor-α and interleukin-6 in the D-HFHC group were significantly up-regulated compared with control groups.ConclusionsThis study presents a novel, non-transgenic, non-surgical method for induction of renal injury in hamsters, which is an important complement to existing diabetic models for pathophysiological studies in early acute and chronic kidney disease, especially hyperlipidemia. These data suggest that both severe hypertriglyceridemia and hypercholesterolemia can accelerate renal injury in the early development of T1DM.Electronic supplementary materialThe online version of this article (doi:10.1186/s12882-015-0041-5) contains supplementary material, which is available to authorized users.
Highlights
Hyperlipidemia is thought to be a major risk factor for the progression of renal diseases in diabetes
The results suggested that type 1 diabetes mellitus (T1DM) model hamsters developed severe hypertriglyceridemia, hypercholesterolemia, proteinuria with mesangial matrix accumulation and produced accelerated renal injury in 4 weeks
The current study suggested that combined dietary fat and cholesterol notably improved plasma total cholesterol (TC) levels in T1DM hamsters more than either fat or cholesterol alone, which was in agreement with STZ-induced diabetes in rats enhancing fat and cholesterol absorption and reducing cholesterol synthesis [38]
Summary
Hyperlipidemia is thought to be a major risk factor for the progression of renal diseases in diabetes. The early effects of triglyceride and cholesterol abnormalities on renal injury in type 1 diabetes mellitus (T1DM) are not fully understood and require reliable animal models for exploration of the underlying mechanisms. Findings from basic and clinical studies strongly suggest that hyperlipidemia can lead to glomerulosclerosis and tubulointerstitial fibrosis and induce renal injury by promoting the intrarenal generation of reactive oxygen species, glomerular infiltration of monocytes and macrophages, and podocyte damage [4] These findings were obtained at stages with extensive renal injury and may have represented secondary effects. Accumulating data from several large scale trials of patients with T2DM point to early lipid abnormality as a major independent risk factor for the development of diabetic nephropathy [10], but the early effects of triglyceride and cholesterol abnormalities on renal injure in T1DM are not fully understood and the mechanisms underlying this need further exploration. One of the reasons is the lack of reliable animal models mimicking severe hypertriglyceridemia and hypercholesterolemia of human T1DM to assist in the understanding of the earlier incidence of diabetic nephropathy
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