Abstract: Objective We investigated the major metabolic changes in low molecular weight serum metabolites of Obesity resistant ratsand control rats, understanding the pathogenesis of non-obese type 2 diabetes. Methods A obesity resistant rat model was constructed and the biochemical criteria were analyzed. The metabolites in the serum were exhaustively separated and detected by GC-MS. Multivariate metabonomics analysis was performed after peak alignment. Results Compared with control rats, the obesity resistant rats showed clear metabolism dysfunctions of glucose, lipid and amino acid, pyruvate, succinate, fumarat, citric acid, myristic acid, uric acid were decreased. And serum sugar, insuline，low-density lipoprotein and total cholesterol was significantly increased,high density lipoprotein, triglyceride decreased significantly. Conclusions After 16 weeks of dietary intervention, the energy metabolism of obesity resistant rats show significant change. The metabolite profiling study could be helpful for understanding mechanism of non-obese type 2 diabetes.

Key words: Obesity resistant, Metabonomics, GC-MS, glucose metabolism