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

Yuko Ishii,Orie Muta,Taiki Fushimi,Nayuta Hirasima,Yasuyuki Fujii,Naomi Osakabe,Minayu Odaka,Tomohiro Teshima

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.

Highlights

Flavan-3-ol (FL)s, a fraction of B-type oligomer procyanidins (Figure 1b) slightly containing catechins (Figure 1c), are enriched in cocoa [1,2], apple [3,4], grape seeds [5,6], and red wine [7,8]
It was well investigated that the browning of adipose tissue is induced by cold exposure [46], exercise [47], and caloric restriction [48]
The results showed that the level of uncoupling protein (Ucp)-1 tended to increase and its mRNA was significantly upregulated in the brown adipose tissue (BAT) of the FLs group (Figure 3a,b)

Summary

Introduction

Flavan-3-ol (FL)s, a fraction of B-type oligomer procyanidins (Figure 1b) slightly containing catechins (Figure 1c), are enriched in cocoa [1,2], apple [3,4], grape seeds [5,6], and red wine [7,8]. Many intervention studies have suggested that the intake of FLs results in beneficial alterations in the metabolism, such as a significant decrease in plasma LDL with an increase in HDL [13,14,15] and a rise in glucose tolerance [16,17,18]. (FLs) the structure of B-type procyanidins (b), thescheme structure of catechins (c), the scheme for the experimental Figure. 1. (a), Composition of flavan-3-ols fraction (FLs) and of experimental procedures. Composition of flavan-3-ols procedure to(FLs) determine catecholamines (CAs) following single dose of FLs (d), of thefor cage urine fraction (a), theurinary structure of B-type procyanidins (b), the astructure of catechins (c), photo the scheme thefor experimental collection (e), the for urinary the experimental procedure examine the impact of repeated administration

Methods

Results

Discussion

Conclusion