Metabolomic study with high fat diet

This study used 1H nuclear magnetic resonance (NMR) spectroscopy to examine the metabolic profiles of plasma and urine from the low-density lipoprotein receptors (LDLR) knockout mice.

Consistent with previous studies, these mice developed hypercholesterolemia and atherosclerosis when fed a high-fat/cholesterol/cholate containing diet. In addition, multivariate statistical analysis of the metabolomic data highlighted significant differences in tricarboxylic acid cycle and fatty acid metabolism, as a result of high-fat/cholesterol diet feeding. The high-fat/cholesterol/cholate diet, LDL receptor gene deficiency, and the diet-genotype interaction caused a significant perturbation in choline metabolism, notably the choline oxidation pathway. Specifically, the loss in the LDL receptor caused a marked reduction in the urinary excretion of betaine and dimethylglycine, especially when the mice are fed a high fat/cholesterol/cholate diet.

These metabolic changes are comparable with those detected in ApoE knockout mice fed the same high-fat/cholesterol/cholate diet and may be useful for monitoring the onset of atherosclerosis across animal models.


Cheng et al (2010). "A metabolomic study of the LDL receptor null mouse fed a high-fat diet reveals profound perturbations in choline metabolism that are shared with ApoE null mice." Physiol. Genomics 41: 224-231.