Multi-Tissue Time-Domain NMR Metabolomics Investigation of Time-Restricted Feeding in Male and Female Nile Grass Rats

Abstract

Metabolic disease resulting from overnutrition is prevalent and rapidly increasing in incidence in modern society. Time restricted feeding (TRF) dietary regimens have recently shown promise in attenuating some of the negative metabolic effects associated with chronic nutrient stress. The purpose of this study is to utilize a multi-tissue metabolomics approach using nuclear magnetic resonance (NMR) spectroscopy to investigate TRF and sex-specific effects of high-fat diet in a diurnal Nile grass rat model. Animals followed a six-week dietary protocol on one of four diets: chow ad libitum, high-fat ad libitum (HF-AD), high-fat early TRF (HF-AM), or high-fat late TRF (HF-PM), and their liver, heart, and white adipose tissues were harvested at the end of the study and were analyzed by NMR. Time-domain complete reduction to amplitude–frequency table (CRAFT) was used to semi-automate and systematically quantify metabolites in liver, heart, and adipose tissues while minimizing operator bias. Metabolite profiling and statistical analysis revealed lipid remodeling in all three tissues and ectopic accumulation of cardiac and hepatic lipids for HF-AD feeding compared to a standard chow diet. Animals on TRF high-fat diet had lower lipid levels in the heart and liver compared to the ad libitum group; however, no significant differences were noted for adipose tissue. Regardless of diet, females exhibited greater amounts of hepatic lipids compared to males, while no consistent differences were shown in adipose and heart. In conclusion, this study demonstrates the feasibility of performing systematic and time-efficient multi-tissue NMR metabolomics to elucidate metabolites involved in the crosstalk between different metabolic tissues and provides a more holistic approach to better understand the etiology of metabolic disease and the effects of TRF on metabolic profiles.