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Published on: February 3, 2023
Repeated Oral Administration of Flavan-3-ols Induces Browning in Mice Adipose Tissues through Sympathetic Nerve
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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