Abstract
BackgroundThe role of renal lipoprotein lipase (LPL) per se in kidney diseases is still controversial and obscure. The purpose of this study was to observe the preventive effects of Ibrolipim, a LPL activator, on lipid accumulation and LPL expression in the kidneys of minipigs fed a high-sucrose and high-fat diet (HSFD).MethodsMale Chinese Bama minipigs were fed a control diet or HSFD with or without 0.1 g/kg/day Ibrolipim for 5 months. Body weight, plasma glucose, insulin, lipids, LPL activity, and urinary microalbumin were measured. Renal tissue was obtained for detecting LPL activity and contents of triglyceride and cholesterol, observing the renal lipid accumulation by Oil Red O staining, and examining the mRNA and protein expression of LPL by real time PCR, Western Blot and immunohistochemistry.ResultsFeeding HSFD to minipigs caused weight gain, hyperglycemia, hyperinsulinemia, hyperlipidemia and microalbuminuria. HSFD increased plasma LPL activity while it decreased the mRNA and protein expression and activity of LPL in the kidney. The increases in renal triglyceride and cholesterol contents were associated with the decrease in renal LPL activity of HSFD-fed minipigs. In contrast, supplementing Ibrolipim into HSFD lowered body weight, plasma glucose, insulin, triglyceride and urinary albumin concentrations while it increased plasma total cholesterol and HDL-C. Ibrolipim suppressed the renal accumulation of triglyceride and cholesterol, and stimulated the diet-induced down-regulation of LPL expression and activity in the kidney.ConclusionsIbrolipim exerts renoprotective and hypolipidemic effects via the increase in renal LPL activity and expression, and thus the increased expression and activity of renal LPL play a vital role in suppressing renal lipid accumulation and ameliorating proteinuria in diet-induced diabetic minipigs.
Highlights
It is increasingly accepted that abnormal lipid metabolism and renal accumulation of lipids play an important role in the pathogenesis of diabetic nephropathy (DN) [1,2,3]
Body weight gain was significantly higher in the high sucrose and fat diet (HSFD) group than in the control diet (CD) group, whereas it was suppressed in the HSFD+Ibrolipim group compared with the HSFD group in the 4th and 5th months (Table 1)
Effects of Ibrolipim on plasma parameters in minipigs As shown in Table 1, plasma glucose, insulin, TG, total cholesterol (TC) and high-density lipoprotein cholesterol (HDL-C) concentrations were significantly increased in the HSFD group over the control group with feeding program
Summary
It is increasingly accepted that abnormal lipid metabolism and renal accumulation of lipids play an important role in the pathogenesis of diabetic nephropathy (DN) [1,2,3]. There are many reports that LPL expression and activity in the heart, skeletal muscle, and adipose tissues are suppressed in humans and experimental animals with kidney disease [15,16,17,18]. In any case, these conflicting results suggest that LPL may be important in mediating the initiation and/or progression of renal disease. The purpose of this study was to observe the preventive effects of Ibrolipim, a LPL activator, on lipid accumulation and LPL expression in the kidneys of minipigs fed a high-sucrose and high-fat diet (HSFD)
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