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

Abstract

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.

Keywords:

• Insulin resistance
• Metabonomics
• Nuclear magnetic resonance (NMR)
• Type 2 diabetes mellitus (T2DM)
• Zucker obese rat

Acknowledgments

This work was supported by the Chinese Academy of Sciences (CAS) Knowledge Creative Program (No. KSCX2-YW-R-118) and the National Science & Technology Major Project (2009ZX09301, 2009ZX09501-001).

Notes

^a Values are expressed as means ± SD. Statistics: *p < 0.05, **p < 0.01 compared with Zucker lean rats (n = 6 for each group).

Key: NAC: N-acetylglycoproteins; 3-HB: 3-hydrobutyrate.

*p < 0.05 and **p < 0.01.