Multiple Univariate Data Analysis Reveals the Inulin Effects on the High-Fat-Diet Induced Metabolic Alterations in Rat Myocardium and Testicles in the Preobesity State

Obesity is a worldwide epidemic and a well-known risk factor for many diseases affecting billions of people’s health and well-being. However, little information is available for metabolic changes associated with the effects of obesity development and interventions on cardiovascular and reproduction systems. Here, we systematically analyzed the effects of high-fat diet (HFD) and inulin intake on the metabolite compositions of myocardium and testicle using NMR spectroscopy. We developed a useful high-throughput method based on multiple univariate data analysis (MUDA) to visualize and efficiently extract information on metabolites significantly affected by an intervention. We found that HFD caused widespread metabolic changes in both rat myocardium and testicles involving fatty acid β-oxidation together with the metabolisms of choline, amino acids, purines and pyrimidines even before HFD caused significant body-weight increases. Inulin intake ameliorated some of the HFD-induced metabolic changes in both myocardium (3-HB, lactate and guanosine) and testicle tissues (3-HB, inosine and betaine). A remarkable elevation of <i>scyllo</i>-inositol was also observable with inulin intake in both tissues. These findings offered essential information for the inulin effects on the HFD-induced metabolic changes and demonstrated this MUDA method as a powerful alternative to traditionally used multivariate data analysis for metabonomics

High-Fat Diet Induces Dynamic Metabolic Alterations in Multiple Biological Matrices of Rats

Obesity is a condition resulting from the interactions of individual biology and environmental factors causing multiple complications. To understand the system’s metabolic changes associated with the obesity development and progression, we systematically analyzed the dynamic metabonomic changes induced by a high-fat diet (HFD) in multiple biological matrices of rats using NMR and GC-FID/MS techniques. Clinical chemistry and histopathological data were obtained as complementary information. We found that HFD intakes caused systematic metabolic changes in blood plasma, liver, and urine samples involving multiple metabolic pathways including glycolysis, TCA cycle, and gut microbiota functions together with the metabolisms of fatty acids, amino acids, choline, B-vitamins, purines, and pyrimidines. The HFD-induced metabolic variations were detectable in rat urine a week after HFD intake and showed clear dependence on the intake duration. B-vitamins and gut microbiota played important roles in the obesity development and progression together with changes in TCA cycle intermediates (citrate, α-ketoglutarate, succinate, and fumarate). 83-day HFD intakes caused significant metabolic alterations in rat liver highlighted with the enhancements in lipogenesis, lipid accumulation and lipid oxidation, suppression of glycolysis, up-regulation of gluconeogenesis and glycogenesis together with altered metabolisms of choline, amino acids and nucleotides. HFD intakes reduced the PUFA-to-MUFA ratio in both plasma and liver, indicating the HFD-induced oxidative stress. These findings provided essential biochemistry information about the dynamic metabolic responses to the development and progression of HFD-induced obesity. This study also demonstrated the combined metabonomic analysis of multiple biological matrices as a powerful approach for understanding the molecular basis of pathogenesis and disease progression