Repeated Oral Administration of Flavan-3-ols Induces Browning in Mice Adipose Tissues through Sympathetic Nerve Activation

Nutrients. 2021 Nov 24;13(12):4214. doi: 10.3390/nu13124214.

Abstract

We previously found increases in uncoupling protein (Ucp)-1 transcription in brown adipose tissue (BAT) of mice following a single oral dose of flavan 3-ol (FL)s, a fraction of catechins and procyanidins. It was confirmed that these changes were totally reduced by co-treatment of adrenaline blockers. According to these previous results, FLs possibly activate sympathetic nervous system (SNS). In this study, we confirmed the marked increase in urinary catecholamine (CA) s projecting SNS activity following a single dose of 50 mg/kg FLs. In addition, we examined the impact of the repeated administration of 50 mg/kg FLs for 14 days on adipose tissues in mice. In BAT, FLs tended to increase the level of Ucp-1 along with significant increase of thermogenic transcriptome factors expressions, such as peroxisome proliferator-activated receptor γ coactivator (PGC)-1α and PR domain-containing (PRDM)1. Expression of browning markers, CD137 and transmembrane protein (TMEM) 26, in addition to PGC-1α were increased in epididymal adipose (eWAT) by FLs. A multilocular morphology with cell size reduction was shown in the inguinal adipose (iWAT), together with increasing the level of Ucp-1 by FLs. These results exert that FLs induce browning in adipose, and this change is possibly produced by the activation of the SNS.

Keywords: adipose; browning; catecholamine; flavan-3-ols; sympathetic nerve.

MeSH terms

  • Adipose Tissue / metabolism*
  • Administration, Oral
  • Animals
  • Catecholamines / urine
  • Flavonoids / administration & dosage*
  • Membrane Proteins / metabolism
  • Mice
  • Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha / metabolism
  • Positive Regulatory Domain I-Binding Factor 1 / metabolism
  • Sympathetic Nervous System / drug effects*
  • Thermogenesis / drug effects
  • Tumor Necrosis Factor Receptor Superfamily, Member 9 / metabolism
  • Uncoupling Protein 1 / metabolism

Substances

  • Catecholamines
  • Flavonoids
  • Membrane Proteins
  • Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha
  • Prdm1 protein, mouse
  • Tmem26 protein, mouse
  • Tumor Necrosis Factor Receptor Superfamily, Member 9
  • Uncoupling Protein 1
  • flavan-3-ol
  • Positive Regulatory Domain I-Binding Factor 1