1H NMR-Based Metabonomic Analysis of Metabolic Changes of Serum and Liver in Zucker Obese Rats

Type 2 diabetes mellitus (T2DM) is characterized by insulin resistance, which is the inability of tissues to respond properly to normal circulating concentrations of insulin in the body. As an extensively used model of insulin resistance and obesity, the Zucker obese rat exhibits an abnormal regulation of glucose, lipids, and other substances metabolized. In this present work, we applied a 1H nuclear magnetic resonance (NMR)-based metabonomic approach to establish metabolic profiles of both sera and liver extracts from Zucker obese rats and addressed the pathological features of T2DM. Principal component analysis (PCA) demonstrated that Zucker obese rats were separated from the control rats in the levels of sera and aqueous soluble liver extracts, indicating that the metabolic characteristics of the two groups are markedly different. Compared with Zucker lean rats, Zucker obese rats displayed higher sera levels of lactate, N-acetylglycoprotein (NAC), trimethylamine, 3-hydrobutyrate (3-HB), acetoacetate, and lipid. Moreover, Zucker obese rats also showed increased levels of alanine, lactate, creatinine, and decreased levels of betaine, glutamate, acetoacetate, 3-HB, and creatine in aqueous soluble liver extracts. Our results reveal significant alterations of both lipid and energy metabolisms, which reflect the pathological features of T2DM. This work may be of benefit to the understanding of the detailed molecular mechanism of T2DM.Chinese Academy of Sciences (CAS)[KSCX2-YW-R-118]; National Science & Technology Major Project[2009ZX09301, 2009ZX09501-001

(1)H-NMR-based metabonomic analysis of metabolic profiling in diabetic nephropathy rats induced by streptozotocin

Zhao L, Gao H, Lian F, Liu X, Zhao Y, Lin D. (1)H-NMR-based metabonomic analysis of metabolic profiling in diabetic nephropathy rats induced by streptozotocin. Am J Physiol Renal Physiol 300: F947-F956, 2011. First published January 12, 2011; doi:10.1152/ajprenal.00551.2010.-Elucidation of the metabolic profiling in diabetic nephropathy (DN) rats is of great assistance for understanding the pathogenesis of DN. In this study, (1)H-nuclear magnetic resonance (NMR)-based metabonomics combined with HPLC measurements was used to quantitatively analyze the metabolic changes in urine and kidney extracts from diabetic 2-wk and 8-wk rats induced by streptozotocin (STZ). Pattern recognition analysis of either urine or kidney extracts indicated that the two diabetic groups were separated obviously from the control group, suggesting that the metabolic profiles of the diabetic groups were markedly different from the control. The diabetic 8-wk rats showed lower levels of creatine, dimethylamine, and higher levels of ascorbate, succinate, lactate, citrate, allantoin, 2-ketoglutarate, and 3-hydrobutyrate (3-HB) in the urine samples. Moreover, the diabetic 8-wk rats displayed lower levels of succinate, creatine, myo-inositol, alanine, lactate, and ATP, and higher levels of 3-HB and glucose in the kidney extracts. The observed metabolic changes imply the enhanced pathways of either lipid or ketone body synthesis and decreased pathways of either tricarboxylic acid cycle or glycolysis in DN rats compared with the control. Our results suggest that the energy metabolic changes are associated with the pathogenic process of DN.National Natural Science Foundation of China[20705037, 30730026]; Chinese Academy of Sciences[KSCX2-YW-R-118, KSCX2-YW-R-104]; Program of Shanghai[09XD1405100