Obesity is a risk factor for many diseases, such as type 2 diabetes and cardiovascular diseases. In line with the need for precision medicine, the search for biomarkers reporting the progression of obesity- and diet-associated disorders is urgent. We used NMR to determine the metabolomics profile of key organs (lung, liver, heart, skeletal muscle, kidney, and brain) and serum from male C57Bl/6J mice (5 weeks old) fed for 6, 10, and 14 weeks on a high-fat and high-sucrose diet (HFHSD) vs. a standard diet (STD). We determined metabolite concentrations in the organs at each time point, which allowed us to discriminate age- and diet-related effects as well as the interactions between both, highlighting the need to evaluate the influence of age as a confounding factor on metabolic signatures. Notably, the analysis revealed the influence of time on metabolite concentrations in the STD condition, probably reflecting the juvenile-to-adult transition. Variations impacted the liver and lung metabolites, revealing the strong influence of the HFHS diet on normal metabolism maturation during youth.

Benchtop NMR is becoming an increasingly important tool, sometimes providing a simple and low-cost alternative to high-field NMR. The Achille’s heel of NMR and even more critically of benchtop NMR is its limited sensitivity. However, when combined with hyperpolarization techniques, the sensitivity boost can provide excellent sensitivity that can even make benchtop NMR compatible with affinity studies for drug discovery. Hyperpolarization by dissolution dynamic nuclear polarization (dDNP) provides a route to enhancing 13C nuclear magnetic resonance (NMR) sensitivity by more than five orders of magnitude for a wide range of small molecules on a benchtop NMR system. We show here how ligands can be secondarily labeled with 13C tags and hyperpolarized with conventional dDNP methods. These hyperpolarized ligands display long nuclear spin-lattice relaxation time constants and can therefore be used to probe interactions with target proteins in conventional dDNP settings. The boost in sensitivity combined with the simplicity of the 13C spectra (one peak per ligand) enables detection on an 80 MHz benchtop NMR spectrometer at micromolar concentrations, which may ultimately provide a way of improving and accelerating the discovery of new drug candidates.