title: Effect of metformin on the urinary metabolites of diet-induced-obese mice studied by ultra performance liquid chromatography coupled to time-of-flight mass spectrometry (UPLC-TOF/MS).
abstract: Obesity is becoming a health concern worldwide and metformin, a first line anti-diabetic drug, was associated with weight loss under different backgrounds. However, most researches focused on the anti-diabetic mechanism and less attention has been paid on the mechanism of weight loss of metformin. Therefore, we established a metabonomic method to evaluate metformin action in preventing obesity in a high fat diet-induced-obesity (DIO) mice model. 36 male C57BL/6 mice (8-week old) were randomly divided into control group (n=12, normal chow), model group (n=12, high fat chow) and metformin group (n=12, high fat chow and dosed with metformin) over 16 weeks. A urinary metabonomic study using UPLC-TOF/MS was performed in combination with multivariate statistical analysis. In addition, indices of body weight and food intake as well as fasting blood glucose, fed blood glucose, oral glucose tolerance test (OGTT) and plasma insulin were collected. Significant weight loss in metformin-treated mice was achieved and 21 potential biomarkers were identified. Decreased glucose, myristic acid, stearidonic acid, lysoPC (16:0), lysoPC (18:0), L-glutamic acid, L-methionine, L-threonine, L-phenylalanine, L-histidine, L-carnitine, L-malic acid and pantothenic acid in urine indicated that metformin may have exerted effects on energy metabolism. Further, based on the biomarkers, we cautiously propose that tricarboxylic acid cycle (TCA) may have been compromised by metformin and might contribute to the activation of adenosine monophosphate kinase (AMPK), then AMPK activation led to more β-oxidation of certain fatty acids and augmented lipolysis and thus induced weight loss. Related cellular and molecular studies are being considered to further investigate the underlying mechanism.
authors.affiliation: Engineering Research Center of Modern Preparation Technology of TCM, Ministry of Education, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, PR China.
authors.forename: Yunyun
authors.initials: Y
authors.lastname: Zhu
authors.forename: Yi
authors.initials: Y
authors.lastname: Feng
authors.forename: Lan
authors.initials: L
authors.lastname: Shen
authors.forename: Desheng
authors.initials: D
authors.lastname: Xu
authors.forename: Bin
authors.initials: B
authors.lastname: Wang
authors.forename: Kefeng
authors.initials: K
authors.lastname: Ruan
authors.forename: Wenjuan
authors.initials: W
authors.lastname: Cong
mesh_terms: D000818:Animals; D001786:Blood Glucose / Q000187:drug effects; D001835:Body Weight / Q000187:drug effects; D002851:Chromatography, High Pressure Liquid / Q000379:methods*; D059305:Diet, High-Fat; D008297:Male; D013058:Mass Spectrometry / Q000379:methods*; D055442:Metabolome / Q000187:drug effects*; D055432:Metabolomics / Q000379:methods; D008687:Metformin / Q000494:pharmacology*; D051379:Mice; D008810:Mice, Inbred C57BL; D008820:Mice, Obese; D009765:Obesity / Q000378:metabolism / Q000652:urine*; D011897:Random Allocation
chemical_list: D001786:Blood Glucose; D008687:Metformin