Preprint Article Version 1 Preserved in Portico This version is not peer-reviewed

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

Version 1 : Received: 15 September 2021 / Approved: 15 September 2021 / Online: 15 September 2021 (15:16:21 CEST)

How to cite: Ishii, Y.; Muta, O.; Teshima, T.; Hirasima, N.; Odaka, M.; Fushimi, T.; Fujii, Y.; Osakabe, N. Repeated Oral Administration of Flavan-3-ols Induces Browning in Mice Adipose Tissues Through Sympathetic Nerve Activation. Preprints 2021, 2021090268 (doi: 10.20944/preprints202109.0268.v1). Ishii, Y.; Muta, O.; Teshima, T.; Hirasima, N.; Odaka, M.; Fushimi, T.; Fujii, Y.; Osakabe, N. Repeated Oral Administration of Flavan-3-ols Induces Browning in Mice Adipose Tissues Through Sympathetic Nerve Activation. Preprints 2021, 2021090268 (doi: 10.20944/preprints202109.0268.v1).

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-ols (FL), 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, FL possibly activates 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 FL. In addition, we examined the impact of the repeated administration of 50 mg/kg FL for 14 days on adipose tissues in mice. In BAT, FL tended to increase the level of Ucp-1 along with thermogenic transcriptome factors, such as peroxisome proliferator-activated receptor γ coactivator (PGC)-1α and PR domain-containing (PRDM)1. Transcription of browning markers, such as CD137 and transmembrane protein (TMEM) 26 in addition to PGC-1α were increased in epididymal adipose (eWAT) by FL. A multilocular morphology with cell size reduction was shown in the inguinal adipose (iWAT), together with increasing the level of Ucp-1 following administration of FL. These results suggest that FL produces browning in adipose through activation of the SNS.

Keywords

flavan-3-ols; adipose; browning; catecholamine; sympathetic nerve

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