Quercetin and Derivatives Ameliorate Metabolic Disturbances by Regulating Gut Metabolite Profiles in Mice with Circadian Rhythm Disruption and High-Fat Diet

Nutrients. 2026 Feb 28;18(5):799. doi: 10.3390/nu18050799.

Abstract

Background: Amidst evolving modern lifestyles characterized by widespread circadian rhythm disturbances and high-fat dietary habits, the incidence of metabolic disorders continues to escalate. In recent years, plant-derived bioactive compounds have attracted considerable interest as therapeutic candidates, with quercetin and its derivatives demonstrating promising potential for the regulation of metabolism.

Methods: This study employed a dual-induction model of metabolic dysregulation, elicited through both circadian rhythm disruption and a high-fat diet, to systematically evaluate the regulatory effects of quercetin and its derivatives on mice through dual stimulation by circadian rhythm disruption and a high-fat diet.

Results and conclusions: Non-targeted fecal metabolomics analysis indicates that quercetin and its derivatives significantly alter the intestinal metabolite profile in mice, alleviating metabolic abnormalities induced by circadian rhythm disruption and high-fat diet. These findings provide a theoretical basis for the future development of quercetin-based functional food products.

Keywords: circadian rhythm disorders; intestinal metabolites; quercetin and its derivatives (isoquercitrin and enzymatically modified isoquercitrin).

MeSH terms

  • Animals
  • Chronobiology Disorders* / metabolism
  • Circadian Rhythm* / drug effects
  • Diet, High-Fat* / adverse effects
  • Feces / chemistry
  • Male
  • Metabolic Diseases* / drug therapy
  • Metabolic Diseases* / etiology
  • Metabolic Diseases* / metabolism
  • Metabolome* / drug effects
  • Metabolomics
  • Mice
  • Mice, Inbred C57BL
  • Quercetin* / analogs & derivatives
  • Quercetin* / pharmacology

Substances

  • Quercetin