Metabolic Status of Lean and Obese Zucker Rats Based on Untargeted and Targeted Metabolomics Analysis of Serum

Abstract

Obesity is growing worldwide epidemic. Animal models can provide some clues about the etiology, development, prevention, and treatment of obesity. We examined and compared serum metabolites between seven lean (L) and seven obese (O) female Zucker rats to investigate the individual serum metabolic profile. A combination of HPLC-UV, HPLC-ECD, and LC-MS revealed more than 400 peaks. The 50 highest quality peaks were selected as the focus of our study. Untargeted metabolomics analysis showed significantly higher mean peak heights for 20 peaks in L rats, generally distributed randomly, except for a cluster (peaks 44-50) where L showed stable dominancy over O. Only eight peaks were significantly higher in O rats. Peak height ratios between pairs of L and O rats were significantly higher at 199 positions in L rats and at 123 positions in O rats. Targeted metabolomics analysis showed significantly higher levels of methionine, cysteine, tryptophan, kynurenic acid, and cysteine/cystine ratio in L rats and significantly higher levels of cystine and tyrosine in O rats. These results contribute to a better understanding of systemic metabolic perturbations in the obese Zucker rat model, emphasizing the value of both whole metabolome and individual metabolic profiles in the design and interpretation of studies using animal models.

Keywords: obesity; serum metabolomics.

Figure 1

Average peak heights in serum from lean (L) and obese (O) Zucker rats (Panel A) and serum peak height ratios in lean (L) and obese (O) Zucker rats (Panel B). (Panel A): Average height of the corresponding 50 peaks was compared between L and O groups. Significantly (p > 0.05) higher average peak intensity in the group. Significantly (p > 0.05) lower average peak intensity in the group. No difference between groups. Marginal (0.1 < p > 0.05) difference between groups. (Panel B): Pairs of 50 peaks intensity ratio between L and O groups. Peak ratio at least 50% higher in the L group. Peak ratio at least 50% higher in the O group. No difference between groups.