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

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.

The Potential of Flavonoids and Flavonoid Metabolites in the Treatment of Neurodegenerative Pathology in Disorders of Cognitive Decline

“…Some flavones and flavone metabolites have been observed to modulate neural processes. Catechin and procyanidin flavan-3-ols are transported by nerves and effect adipose tissue mediated nerve activation [ 101 ]. The flavonoid isoliquiritigenin activates GABA B receptors, decreasing entry of Ca 2+ into rat cerebrocortical nerves through voltage-gated Ca 2+ channels, affecting glutamate transport and release from synaptic vesicles, and the transduction of neurotransmitters in neural networks [ 102 ].…”

Sensory Nutrition and Bitterness and Astringency of Polyphenols

“…Polyphenols appear to have a similar effect to GLP-1 agonists in weight loss by suppressing appetite and reducing gastric emptying [187,188]. Increased sympathetic activity after ingestion of astringent polyphenols is thought to cause fat browning, as confirmed in the study using rodents [118]. In addition, this promotion of lipid oxidation induced by the consumption of astringent polyphenols has also been shown to increase HDL cholesterol levels in the blood [189,190].…”

“…Repeated administration of the flavanol cinnamtannin A2 (A2, epicatechin tetramer) for two weeks also resulted in significant activation of the Akt/mTOR pathway and a marked increase in the mean muscle cross-sectional area in the soleus muscle [119] as similar to adrenalin agonist clenbuterol [120]. It has also been observed that after a single dose of flavanol, blood catecholamine levels were significantly increased [121] and urinary catecholamine excretion was also elevated [118]. These results confirm that FL induces sympathetic hyperactivity (Figure 2b).…”

“…After being administered a flavanol fraction from cocoa for two weeks, browning was shown in mice inguinal adipose tissue. This was characterized by multilocular lipid droplets, a marked reduction in adipocyte size and increased expression of the heat-producing protein, uncoupling protein 1 (UCP-1) [118]. Repeated administration of the flavanol cinnamtannin A2 (A2, epicatechin tetramer) for two weeks also resulted in significant activation of the Akt/mTOR pathway and a marked increase in the mean muscle cross-sectional area in the soleus muscle [119] as similar to adrenalin agonist clenbuterol [120].…”