Effect of quercetin on nonshivering thermogenesis of brown adipose tissue in high-fat diet-induced obese mice

J Nutr Biochem. 2021 Feb:88:108532. doi: 10.1016/j.jnutbio.2020.108532. Epub 2020 Oct 29.


Activating nonshivering thermogenesis in brown adipose tissue (BAT) is a promising strategy to prevent obesity. This study investigated whether quercetin supplementation improves obesity in mice by increasing nonshivering thermogenesis in BAT and white adipose tissue (WAT) browning. Compared to high-fat diet (HFD)-fed mice, mice fed a HFD supplemented with 1% quercetin (HFDQ) had reduced body weight and total plasma cholesterol. In HFDQ-fed mice, retroperitoneal WAT (RWAT) weight was decreased, and browning effect and lipolysis were increased. HFDQ-fed mice had increased expression of nonshivering thermogenesis genes in BAT, including uncoupling protein 1 (UCP1), peroxisome proliferator-activated receptor-gamma coactivator 1α (PGC1α), cell death-inducing DFFA-like effector A (CIDEA), and mitochondrial transcriptional factor A (mtTFA). Quercetin supplementation increased genes and proteins in β3-adrenergic receptor (ADRB3), p38 mitogen-activated protein kinase (MAPK), and AMP-activated protein kinase (AMPK) pathways in HFD-fed mice, which were suppressed by an AMPK inhibitor or an ADRB3 antagonist. Energy expenditure and core body temperature were not changed by quercetin, but physical activity was increased in HFDQ mice during dark periods at room and cold temperatures. Quercetin also decreased the Firmicutes to Bacteroidetes ratio and increased short-chain fatty acid production in the feces of HFD-fed mice. In summary, quercetin supplementation in HFD-fed mice may attenuate obesity. Although the study did not show consistency in data at molecular and pathophysiological levels between BAT function and obesity, it also shows promising health effects of quercetin, accompanied by improved physical activity and gut microbiota dysbiosis.

Keywords: AMP-activated protein kinase; brown adipose tissue; quercetin; uncoupling protein 1.

Publication types

  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • AMP-Activated Protein Kinases / metabolism
  • Adipose Tissue, Brown / metabolism*
  • Adipose Tissue, White / metabolism
  • Animals
  • Cholesterol / blood
  • DNA-Binding Proteins / metabolism
  • Diet, High-Fat / adverse effects
  • Energy Metabolism / drug effects
  • Lipolysis
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Obese
  • Mitochondrial Proteins / metabolism
  • Obesity / metabolism*
  • Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha / metabolism
  • Quercetin / pharmacology*
  • Receptors, Adrenergic, beta-3 / metabolism
  • Thermogenesis / drug effects*
  • Transcription Factors / metabolism
  • Uncoupling Protein 1 / metabolism


  • DNA-Binding Proteins
  • Mitochondrial Proteins
  • Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha
  • Receptors, Adrenergic, beta-3
  • Transcription Factors
  • Uncoupling Protein 1
  • mitochondrial transcription factor A
  • Cholesterol
  • Quercetin
  • AMP-Activated Protein Kinases