*4.3. 1H-NMR Metabolomics*

The high-resolution magic-angle spinning nuclear magnetic resonance (HR-MAS NMR) spectra were recorded using an Agilent 600 MHz spectrometer that was equipped with a 4 mm gHX NanoProbe (Agilent Technologies, Santa Clara, CA, USA). All spectra were acquired at 600.167 MHz. The acquisition time was 1.703 s, relaxation delay was 1 s, and a total of 128 scans was obtained. The Carr-Purcell-Meiboom-Gill (CPMG) pulse sequence was used for the suppression of water and compounds with high molecular mass. For data processing, Chenomx NMR Suit 7.1 professional with the Chenomx 600 MHz library database were used (Chenomx Inc., Edmonton, AB, Canada). The bin size for spectra was 0.001 ppm. The binning data were normalized to the total area. PCA, partial least-squares discriminant analysis (PLS-DA), and orthogonal partial least-squares discriminant analysis (OPLS-DA) were performed using SIMCA-P+ 12.0 (Umetrics, Malmö, Sweden). For visualization of VIP scores of metabolites and Metabolic Set Enrichment Analysis, web-based software MetaboAnalyst 3.0 (http://www.metaboanalyst.ca) was used.
