A Boost in Mitochondrial Activity Underpins the Cholesterol-Lowering Effect of Annurca Apple Polyphenols on Hepatic Cells

Abstract

Reduction in cholesterol blood levels represents one of the therapeutic goals to achieve in order to reduce the occurrence of cardiovascular diseases. Commonly, this goal is attempted by promoting healthy lifestyle behaviors and low-fat diets. Recently, several nutraceuticals have been shown to possess cholesterol-lowering properties and are becoming common over the counter products. Among others, apple polyphenols efficiently lower total cholesterol levels in humans and impact overall lipid metabolism. Malus Pumila Miller cv Annurca is an apple native to Southern Italy presenting one of the highest content of procyanidin B2, a dimeric procyanidin. Tested in clinical trials, the oral consumption of an Annurca polyphenolic extract (AAE) exerted a cholesterol-lowering effect similar to the statins Atorvastatin and Simvastatin. Despite AAE activity, the analysis of the molecular mechanism behind its cholesterol-lowering effect is unclear. Using isotope labeling and high-resolution mass spectrometry approaches we here performed a metabolic profiling of in vitro cultured human hepatocytes treated with AAE to reveal its mechanism of action. The results show that AAE acts differently than statins. The extract reprograms hepatic cell metabolism and promotes mitochondrial respiration, lipolysis and fatty acid β-oxidation. Citrate and acetyl-CoA, both necessary for the production of cholesterol, are diverted to the Krebs Cycle by AAE, that, ultimately, lowers cholesterogenesis and fatty acid synthesis.

Proanthocyanidins and Where to Find Them: A Meta-Analytic Approach to Investigate Their Chemistry, Biosynthesis, Distribution, and Effect on Human Health

“…Other signaling pathways influenced by PACs involve cholesterol metabolism and catabolism. Under high fat intake, procyanidin B2 from Annurca apples reduces cholesterol synthesis by diverting citrate and acetyl-CoA to the Krebs cycle [ 319 ]. Concomitantly, it lowers fatty acid synthesis and promotes lipolysis and fatty acid β-oxidation thanks to a boost in mitochondrial activity [ 319 ].…”

Impact of Polyphenolic-Food on Longevity: An Elixir of Life. An Overview

“…The intake of apples can significantly reduce the danger of lung cancer, particularly in women. Numerous diverse researches have observed that the apple is active in slowing down the oxidation of low-density lipoproteins [ 195 ]. Apple polyphenolic compounds improved the lifespan of fruit flies by 10%.…”

The Pomace Extract Taurisolo Protects Rat Brain From Ischemia-Reperfusion Injury

“…Rat brains were homogenized using a potter in 1 ml of pre-chilled methanol/water 1:1 solution, containing 10 nmol of internal standard, and centrifuged at 10,000 g for 10 min at 4 • C (Ser et al, 2015). The resulting supernatants were collected and transferred into Eppendorf tubes and stored at −80 • C. Analyses were performed according to a previous protocol (Sommella et al, 2019). Data were acquired on a SolariX XR 7T (Bruker Daltonics, Bremen, Germany).…”