Bioactives From Coffee By-Products Stimulate Liver Metabolism and Mitochondrial Bioenergetics via AMPK/PGC-1α/Nrf2 and IRS/AKT/GLUT2 Pathways In Vitro

Abstract

ObjectivesThis study aimed to investigate the effect of the main bioactive compounds from the coffee silverskin and coffee husk on hepatic lipid and glucose metabolism and mitochondrial bioenergetics using an in vitro model mimicking non-alcoholic fatty liver disease. MethodsHepG2 cells were treated with 50 μmol L–1 caffeine, chlorogenic, caffeic, protocatechuic, or gallic acids, or kaempferol, or the aqueous extracts from the coffee silverskin (CSE, 100 μg mL–1) or the coffee husk (CHE, 100 μg mL–1) in the presence of palmitic acid (500 μmol L–1). Cell metabolism biomarkers were assessed 24 h after the co-treatment in cell lysates and supernatants using chemical and immunochemical techniques. Differences among treatments were considered significant at p < 0.05. ResultsBioactive compounds in coffee by-products, CSE, and CHE decreased lipid accumulation (53–115%) by reducing fatty acid synthase expression (44–76%) and stimulated β-oxidation by triggering carnitine palmitoyltransferase I activity (1.6 to 2.6-fold) and up-phosphorylating AMP-activated protein kinase (AMPK, 1.5–2.4-fold). Glucose uptake was promoted via the increase in the insulin receptor substrate (IRS)-1 (1.5 to 2.1-fold) and protein kinase B (Akt1, 1.7–2.4-fold) phosphorylation, and glucose transporter (GLUT)-2 expression (2.1 to 3.7-fold). Mitochondrial function was enhanced (ATP production and O2 consumption rate, 1.7–2.5-fold and 1.8 to 2.5-fold, respectively), and oxidative phosphorylation complexes and peroxisome proliferator-activated receptor-γ coactivator (PGC)-1α expression restored (30–105%). Oxidative stress was diminished (56 – 85%) through augmented superoxide dismutase (1.3 to 1.7-fold) and catalase (1.5 to 2.0-fold) activities, and nuclear factor-erythroid 2-related factor 2 (Nrf2) expression (2.3 to 3.8-fold). ConclusionsThe major bioactive compounds in coffee by-products, primarily chlorogenic and protocatechuic acids, could regulate hepatic lipid and glucose metabolism and prevent oxidative stress and mitochondrial dysfunction by activating AMPK/PGC-1α/Nrf2 and IRS/AKT/GLUT2 signaling pathways. Altogether, our results suggest the use of coffee by-products as a sustainable source of natural bioactives to counteract non-alcoholic fatty liver disease. Funding SourcesUSDA-NIFA-HATCH and the Spanish Ministry of Science and Innovation.