Activating Effects of the Bioactive Compounds From Coffee By-Products on FGF21 Signaling Modulate Hepatic Mitochondrial Bioenergetics and Energy Metabolism in vitro

Abstract

Coffee by-products contain bioactive compounds that have been shown to have the capacity to modulate human metabolism. The goal of this study was to investigate the effects of the main bioactive compounds in coffee by-products and two aqueous extracts from the coffee husk and silverskin on the activation of fibroblast growth factor 21 (FGF21) signaling and the subsequent regulation of mitochondrial bioenergetics and lipid and glucose metabolism. HepG2 cells treated with palmitic acid (PA) were used in a non-alcoholic fatty liver disease (NAFLD) cell model. The bioactive compounds from coffee by-products (50 μmol L−1) and the aqueous extracts from the coffee silverskin and coffee husk (100 μg mL−1) increased ERK1/2 phosphorylation and the secretion of FGF21 (1.3 to 1.9-fold). Coffee by-products' bioactive compounds counteracted inflammation and PA-triggered lipotoxicity. Oxidative stress markers (ROS, mitochondrial superoxide, and NADPH oxidase) and the activity of antioxidant enzymes (superoxide dismutase and catalase) were modulated through the activation of Nrf2 signaling. Mitochondrial bioenergetics were regulated by enhancing respiration and ATP production via PGC-1α, and the expression of oxidative phosphorylation complexes increased. Coffee by-products' bioactive compounds decreased lipid accumulation (23–41%) and fatty acid synthase activity (32–65%) and triggered carnitine palmitoyltransferase-1 activity (1.3 to 1.7-fold) by activating AMPK and SREBP-1c pathways. The GLUT2 expression and glucose uptake were increased (58–111%), followed by a promoted glucokinase activity (55–122%), while glucose production and phosphoenolpyruvate carboxykinase activity were reduced due to IRS-1/Akt1 regulation. The bioactive compounds from coffee by-products, primarily chlorogenic and protocatechuic acids, could regulate hepatic mitochondrial function and lipid and glucose metabolism by activating FGF21 and related signaling cascades.

Brown Adipose Tissue, Batokines, and Bioactive Compounds in Foods: An Update

“…[ 96 ] In “in vitro” models, treatments with coffee and its derived bioactive compounds it increased the signaling of the batokine FGF21, improving glucose uptake and increasing beta‐oxidation and mitochondrial bioenergetics, contributing to a healthy metabolic profile. [ 97 ] Diet‐induced obese mice that received coffee daily at a concentration of 1% w/w rich in chlorogenic acids and caffeine (571.9 and 653.1 mg kg −1 of diet respectively) for 10 weeks, showed a reduction in body mass and EI and an increase in EE. In BAT, coffee bypassed the whitening, restoring its multilocularity in the high‐fat diet (HFD) induced obesity model.…”

Selected Soybean Varieties Regulate Hepatic LDL-Cholesterol Homeostasis Depending on Their Glycinin:β-Conglycinin Ratio

“…Then, they were incubated in EMEM supplemented with 10% FBS in the absence (nontreated cells controls, NT) or presence of FFAs (500 µmol L −1 oleic:palmitic acid, 2:1) conjugated in BSA (1%), and the digested soybean varieties (V1, V3, V9, V17, and V18; 10-1000 µg protein mL −1 ) or simvastatin (0.10-10 µg mL −1 ; 0.24-24 µmol L −1 ). After 24 h treatment, supernatants were collected, centrifuged, and stored at −80 • C until being used as described earlier [29]. Once the half maximal inhibitory concentration (IC 50 ) for cholesterol concentration increase was determined, cells were cultivated in the absence (non-treated cells controls, NT) or presence of FFAs (500 µmol L −1 oleic:palmitic acid, 2:1) and the digested soybean varieties (V1, V3, V9, V17, and V18 at IC 50 s 253, 160, 76, 64, and 146 µg protein mL −1 , respectively) or simvastatin (IC 50 = 160 ng mL −1 ).…”

Can coffee silverskin be a useful tool to fight metabolic syndrome?

“…Likewise, a recent work suggested that aqueous extracts from coffee silverskin (125 μg/mL) stimulated phosphatidylinositol 3-kinase (PI3K) and AMPK signaling ( 66 ). The effect on insulin and PI3K pathways improved hepatic cell insulin sensitivity ( in vitro ), and diminished lipogenesis and gluconeogenesis ( 67 ). In this regard, ferulic acid, an important metabolite of feruloylquinic acids, has been shown to increase the expression levels of PI3-K and GLUT4, thereby increasing glucose uptake in adipocytes ( 55 ).…”

“…A recent study, using aqueous extract of coffee silverskin on hepatic cells (10 to 500 μg/mL), suggested that bioactive compounds, particularly CGA, may regulate glucose metabolism and prevent the development of NAFLD by preventing hyperglycemia and systemic insulin resistance ( 67 ).…”