대한신장학회

논문분류	춘계학술대회 초록집
제목	Adiporon Ameliorates Diabetic Nephropathy in db/db Mice through Improving Ceramide-Dependent Lipotoxicity
저자	Sun Ryoung Choi* 1, Cheol Whee Park2, Ji Hee Lim2, Min Young Kim2, Yaeni Kim2, You Ah Hong2, Hoon Suk Park2, Sungjin Chung2, Seok Joon Shin2, Hyung Wook Kim2, Beom Soon Choi2, Yong-Soo Kim2, Yoon Sik Chang2
출판정보	2016; 2016(1):
키워드	Adiporon, Ceramide-Dependent Lipotoxicity, Diabetic Nephropathy in db/db Mice
초록	Background: The accumulation of lipid and its metabolites in tissues, including the kidney, causes lipotoxicity. Sphingolipids such as ceramides are particularly deleterious. Lowering the accumulation of ceramide can improve metabolic damage of various tissues. Recent reports showed that adiponectin receptors (AdipoRs) have sequence homology with ceramidase enzymes, and an increase of ceramidase activity with overexpression of adiponectin in mice improves ceramide-dependent lipotoxicity. Therefore, we investigated the possible roles of Adiporon, which mimics the effects of adiponectin, in the view of prevention and development of diabetic nephropathy in diabetic mouse model. Methods: Male db/db mice and db/m controls were fed either a regular diet chow or a diet containing adiporon (30 mg/kg/day p.o. for 4 weeks from 17 to 20 weeks of age). Serum, urine and renal tissue specimen were obtained to analyze for changes in metabolic parameters, relevant molecular levels and their association with regard to structural influence. Results: Adiporon fed db/db mice showed decreased amount of albuminuria with no significant changes in the levels of serum adiponectin, glucose and creatinine and it seems to be weight neutral. Adioporon also decreased mesangial matrix expansion and fibrosis, inflammation cell infiltration and accumulations of free fatty acid, triglycerides and ceramide in the kidney. In the molecular level, increased expressions of AdipoR1 and AdipoR2 and acid ceramidase activity in the renal cortex were observed in db/db mice with Adiporon administration. Consistent up-regulations of phosphorylated AMPK and PPAR-α level were associated within the same group. Subsequent improvement of enhanced lipid metabolism and decrement of cellular apoptosis with adiporon treatment were also noted. Conclusion: Adiporon may control oxidative stress in glomerulus through AMPK and PPAR-α activated pathway and further contribute to prevent deterioration of renal function. The protective role of adiporon against the development of diabetic nephropathy seems to occur through a direct action on the kidney independently of systemic effects of adiponectin. Its reduction of lipotoxicity provides protection against albuminuria and renal damage thereby ameliorating endothelial dysfunction in diabetic nephropathy. Our results suggest adiporon as a promising therapeutic agent of diabetic nephropathy through ameliorating ceramide-dependent lipotoxicity.
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