Repeated Oral Administration of Flavan-3-ols Induces Browning in Mice Adipose Tissues through Sympathetic Nerve Activation
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Updated: Oct 8, 2025
Differentiation and Imaging of Brown Adipocytes from the Stromal Vascular Fraction of Interscapular Adipose Tissue from Newborn Mice
Published on: February 3, 2023
Yuko Ishii1, Orie Muta1, Tomohiro Teshima1
1Functional Control Systems, Graduate School of Engineering and Science, Shibaura Institute of Technology, 307 Fukasaku, Minumaku, Saitama 337-8570, Japan.
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.
Insights
Flavan 3-ols (FLs) activate the sympathetic nervous system (SNS), increasing uncoupling protein 1 (Ucp-1) and promoting the browning of adipose tissue. This suggests FLs may enhance thermogenesis and metabolic health.
Area of Science:
- Biochemistry
- Metabolism
- Endocrinology
Background:
- Flavan 3-ols (FLs), found in catechins and procyanidins, were previously shown to increase uncoupling protein 1 (Ucp-1) transcription in brown adipose tissue (BAT).
- These effects were abolished by adrenaline blockers, suggesting FLs activate the sympathetic nervous system (SNS).
Purpose of the Study:
- To confirm FLs activate the SNS by measuring urinary catecholamines (CAs).
- To investigate the effects of repeated FL administration on adipose tissues in mice.
Main Methods:
- Mice were administered a single dose of 50 mg/kg FLs, and urinary CAs were measured.
- Mice received repeated administration of 50 mg/kg FLs for 14 days.
- Adipose tissues (BAT, eWAT, iWAT) were analyzed for Ucp-1 levels, thermogenic gene expression, and morphological changes.
Main Results:
- Single FL dose increased urinary CAs, confirming SNS activation.
- Repeated FL administration increased Ucp-1 levels and thermogenic factors (PGC-1α, PRDM1) in BAT.
- FLs increased browning markers (CD137, TMEM26, PGC-1α) in epididymal adipose tissue (eWAT).
- Inguinal adipose tissue (iWAT) showed multilocular morphology, reduced cell size, and increased Ucp-1.
Conclusions:
- FLs activate the SNS, leading to increased Ucp-1 expression and thermogenic gene activation in adipose tissues.
- FLs induce adipose tissue browning, potentially mediated by SNS activation.
- These findings suggest FLs may play a role in modulating metabolism through adipose tissue adaptation.
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