Most herbal
polyphenols and
flavonoids reveals multiple ameliorative benefits for
obesity caused by chronic metabolic disorders. Accumulated studies have revealed that preferable
therapeutic effects can be obtained through clinical combination of these two kinds of natural compounds for
obesity improvement. The typical representative research was the combination of
quercetin and
resveratrol (CQR), in which the ratio of
quercetin and
resveratrol is 2:1, demonstrating a synergistic effect in anti-
obesity process. Although there exists reports clarifying the mechanism of the combination of two to improve
obesity from the perspective of improving adipose tissue
inflammation or modulating the composition of intestinal flora, there are few further studies on the mechanism of drug action from the perspective of metabolites transformation. In this research, we mainly focused on the alterations of endogenous metabolites in rats, and analyzed the urine metabolites of obese and intervention model. Therefore, a gas chromatography-mass spectrometry (GC-MS) based metabolomics approach was applied to assess the potential effects and mechanisms of CQR at different dosages (45, 90, and 180 mg/kg) in high fat diet (HFD)-induced
obesity rats.
Body weight gain and visceral fat weight were reduced by CQR, as well as blood
lipid and inflammatory factor levels were increased by CQR in a dose-related manner. Urinary metabolomics revealed 22 differential metabolites related to the HFD-induced
obesity, which were reversed in a dose-dependent manner by CQR, of which 8 were reversed in the 45 mg/kg CQR group, 15 were reversed in the 90 mg/kg CQR group, and 18 were reversed in the 180 mg/kg CQR group. Combined with bioinformatics and pattern recognition, the results demonstrated that the key differential metabolites were basically involved in
amino acid metabolism,
galactose metabolism, pantothenate
and CoA biosynthesis,
pyruvate metabolism and
lysine degradation. In summary, our results showed significant therapeutic action by CQR administration and remarkable metabolomic changes after HFD feeding and CQR intervention. Urinary metabolomic analysis was highlighted on account of providing holistic and comprehensive insights into the pathophysiological mechanisms of the HFD-induced
obesity, which also supplied clues for the future mechanism studies of CQR's anti-
obesity effects.