A single oral dose of flavan-3-ols enhances energy expenditure by sympathetic nerve stimulation in mice

• Flavan 3-ols (FL) increase energy expenditure (EE), pAMPK, PGC-1α and UCPs.
• Rising EE, muscle pAMPK and UCP-3 by FL was reduced by β2 adrenaline blocker (ARB).
• Increase of EE, brown adipose PGC-1α and UCP-1 by FL was reduced by β3-ARB.
• Rising UCPs and PGC-1α by FL was reduced by β3 and β2-ARB, but not EE and pAMPK.

Numerous clinical studies have found that ingestion of chocolate reduces the risk of metabolic syndrome, however, the mechanisms were remain unclear. We have reported that a single dose of a flavan-3-ol fraction derived from cocoa (FL) enhanced energy expenditure (EE) and increased the mRNA expression levels of uncoupling proteins (UCPs) and peroxisome proliferator-activated receptor gamma coactivator-1 alpha (PGC-1α), and the protein level of phosphorylated AMP-activated protein kinase (AMPK)α in tissues, along with plasma adrenaline level. In the present study, we examined whether the EE enhancing activity of FL is mediated by adrenergic effect using several adrenalin receptor (AR) blockers. In the first study, mice were butoxamine, as β2AR blocker, with vehicle or 10 mg/kg FL orally. We found that pretreatment with butoxamine prevented the increases of EE, the mRNA expression of UCP-3, and phosphorylated AMPKα that were induced in the gastrocnemius muscle of mice by 10 mg/kg FL. Secondly, mice were given SR52930, as β3AR blocker. Pretreatment with SR52930 prevented the increases of EE, the mRNA expression of UCP-3, and phosphorylated AMPKα that were induced in the gastrocnemius muscle of mice by 10 mg/kg FL. Pretreatment with a combination of both blockers also reduced the increments in mRNA expression levels of UCPs and PGC-1α, however, phosphorylated AMPKα in skeletal muscle was rather increased. These results suggest that the ability of a single oral dose of FL to enhance metabolic activity is mediated by sympathetic nerve system (SNS).

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