The Changes of Serum Metabolites in Diabetic GK Rats after Ileal Transposition Surgery
Ileal transposition (IT) surgery could improve metabolism. Metabolomics has been applied comprehensively in analyzing the global dynamic alterations of metabolites. In the present study, we aimed to investigate serum metabolite alterations in diabetic Goto-Kakizaki (GK) rats after IT surgery.
Male GK rats were subjected to IT and Sham-IT surgery. Six weeks later, body weight, food intake, fat mass, and serum biochemical parameters were measured. The serum metabolomic fingerprint was analyzed using ultra-performance liquid chromatography–mass spectrometry (LC-MS)-based, non-targeted metabolomic approach. The differential metabolites were identified using principal component analysis and orthogonal partial least squares discriminant analysis. Metabolic pathway analysis was performed using HMDB and KEGG databases.
The body weight, food intake, fat mass, serum levels of glucose and insulin, and homeostasis model assessment of insulin resistance (HOMA-IR) of IT rats were significantly decreased when compared with Sham-IT rats (all P < 0.05). In the metabolomics analysis, ten serum differential metabolites were identified. Compared with Sham-IT rats, serum LysoPC(O-18:0) and PG(20:4/20:0) of IT rats were decreased, while genistein 4′-O-glucuronide, 5,6:8,9-Diepoxyergost-22-ene-3,7beta-diol, PI(16:0/18:2(9Z,12Z)), docosapentaenoic acid, 3-Oxo-4,6-choladienoic acid, 3-Oxocholic acid, and TG were increased. Pathway analysis highlighted the following pathways: ether lipid metabolism, alpha linolenic acid and linolenic acid metabolism, incretin synthesis and secretion, free fatty acid receptors, and biosynthesis of unsaturated fatty acids.
IT surgery could significantly decrease body weight and fat mass and improve glucose metabolism in diabetic GK rats. These beneficial effects might be related to the changes of serum metabolites which involved in lipid metabolism, bile acids, and incretin.
KeywordsIleal transposition (IT) surgery Metabolomics Fat mass Liquid chromatography–mass spectrometry (LC-MS) Goto-Kakizaki (GK) rats
The study was supported by grants from the National Natural Science Foundation of China (No. 81400797 for Weijie Chen, No. 30600836, 81471024 for Huijuan Zhu, No. 30540036, 30771026, 81370898 for Fengying Gong), the Beijing Natural Science Foundation (No. 7082079, 7182130 for Fengying Gong), the National Key Program of Clinical Science (WBYZ2011-873 for Fengying Gong and Huijuan Zhu), and the PUMCH Foundation (2013-020 for Fengying Gong).
Compliance with Ethical Standards
All animal experimental procedures were approved by the ethics committee of Peking Union Medical College Hospital.
Conflict of Interest
The authors declare that they have no conflict of interest.
- 5.Sun X, Zheng M, Song M, et al. Ileal interposition reduces blood glucose levels and decreases insulin resistance in a type 2 diabetes mellitus animal model by up-regulating glucagon-like peptide-1 and its receptor. Int J Clin Exp Pathol. 2014;7(7):4136–42.Google Scholar
- 10.Cummings BP, Strader AD, Stanhope KL, et al. Ileal interposition surgery improves glucose and lipid metabolism and delays diabetes onset in the UCD-T2DM rat. Gastroenterology. 2010;138(7):2437–46, 2446.e1.Google Scholar
- 11.Chelikani PK. Ileal transposition surgery: mechanisms of weight loss and diabetes improvements. In: Faintuch J, Faintuch S, editors. Obesity and diabetes. Cham: Springer; 2015. p. 143–52.Google Scholar
- 12.Guo Q, Zhang Q-Q, Chen J-Q, et al. Liver metabolomics study reveals protective function of Phyllanthus urinaria against CCl 4 -induced liver injury. Chin J Nat Med. 2017;15(7):525–33.Google Scholar
- 36.Flachs P, Rossmeisl M, Fau-Kopecky J, et al. The effect of n-3 fatty acids on glucose homeostasis and insulin sensitivity. Physiol Res. 2014;63(Suppl 1):S93–118.Google Scholar