Abstract
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.
Highlights
With the generation of the first New Zealand obese (NZO) mouse strain in 1948, a polygenic mouse model entered the diabetes research field which in comparison to monogenic db/db and ob/ob mice has been much less studied and for which “omics studies” are rare [1]
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
Summary
With the generation of the first New Zealand obese (NZO) mouse strain in 1948, a polygenic mouse model entered the diabetes research field which in comparison to monogenic db/db and ob/ob mice has been much less studied and for which “omics studies” are rare [1]. We studied the monogenic db/db and ob/ob mouse models [2] as well as a mouse model of diet-induced obesity (DIO) [3]. These served as comparative models to elicit and evaluate strengths and weaknesses of the inbred NZO mouse strain to study obesity-induced type 2 diabetes mellitus (T2DM). These models all develop obesity, they differ in their susceptibility to developing diabetes. It was shown that oestrogen decreases hyperphagia via hypothalamic stimuli and leads to enhanced glucose tolerance, higher insulin sensitivity, and an improved β-cell integrity [8]
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