TY - JOUR
T1 - Acylcarnitine Profiles in Plasma and Tissues of Hyperglycemic NZO Mice Correlate with Metabolite Changes of Human Diabetes
AU - Weiser, Anna
AU - Giesbertz, Pieter
AU - Daniel, Hannelore
AU - Spanier, Britta
N1 - Publisher Copyright:
© 2018 Anna Weiser et al.
PY - 2018
Y1 - 2018
N2 - The New Zealand obese (NZO) mouse is a polygenic model for obesity and diabetes with obese females and obese, diabetes-prone males, used to study traits of the metabolic syndrome like type 2 diabetes mellitus (T2DM), obesity, and dyslipidaemia. By using LC-MS/MS, we here examine the suitability of this model to mirror tissue-specific changes in acylcarnitine (AC) and amino acid (AA) species preceding T2DM which may reflect patterns investigated in human metabolism. We observed high concentrations of fatty acid-derived ACs in 11 female mice, high abundance of branched-chain amino acid- (BCAA-) derived ACs in 6 male mice, and slight increases in BCAA-derived ACs in the remaining 6 males. Principal component analysis (PCA) including all ACs and AAs confirmed our hypothesis especially in plasma samples by clustering females, males with high BCAA-derived ACs, and males with slight increases in BCAA-derived ACs. Concentrations of insulin, blood glucose, NEFAs, and triacylglycerols (TAGs) further supported the hypothesis of high BCAA-derived ACs being able to mirror the onset of diabetic traits in male individuals. In conclusion, alterations in AC and AA profiles overlap with observations from human studies indicating the suitability of NZO mice to study metabolic changes preceding human T2DM.
AB - The New Zealand obese (NZO) mouse is a polygenic model for obesity and diabetes with obese females and obese, diabetes-prone males, used to study traits of the metabolic syndrome like type 2 diabetes mellitus (T2DM), obesity, and dyslipidaemia. By using LC-MS/MS, we here examine the suitability of this model to mirror tissue-specific changes in acylcarnitine (AC) and amino acid (AA) species preceding T2DM which may reflect patterns investigated in human metabolism. We observed high concentrations of fatty acid-derived ACs in 11 female mice, high abundance of branched-chain amino acid- (BCAA-) derived ACs in 6 male mice, and slight increases in BCAA-derived ACs in the remaining 6 males. Principal component analysis (PCA) including all ACs and AAs confirmed our hypothesis especially in plasma samples by clustering females, males with high BCAA-derived ACs, and males with slight increases in BCAA-derived ACs. Concentrations of insulin, blood glucose, NEFAs, and triacylglycerols (TAGs) further supported the hypothesis of high BCAA-derived ACs being able to mirror the onset of diabetic traits in male individuals. In conclusion, alterations in AC and AA profiles overlap with observations from human studies indicating the suitability of NZO mice to study metabolic changes preceding human T2DM.
UR - http://www.scopus.com/inward/record.url?scp=85054740060&partnerID=8YFLogxK
U2 - 10.1155/2018/1864865
DO - 10.1155/2018/1864865
M3 - Article
C2 - 29854816
AN - SCOPUS:85054740060
SN - 2314-6745
VL - 2018
JO - Journal of Diabetes Research
JF - Journal of Diabetes Research
M1 - 1864865
ER -