Introduction Although nonalcoholic fatty liver disease (NAFLD) represents the most common cause of chronic liver disease worldwide, its molecular mechanisms are still under investigation and effective therapies are still far from being available [1]. Two natural polyphenols, Quercetin (Que) and Hydroxytyrosol (HT), are known to have a protective effect against the development of NAFLD and in the reduction of intrahepatic lipogenesis due to their antioxidant and hypolipidemic activities [2,3]. In this work, we leverage a NAFLD-on-a-Chip model to investigate the beneficial effect of the two aforementioned polyphenols on the development of hepatic steatosis, providing novel strategies to contrast the onset and progression of the disease and to face the challenges of drug screening [4]. Experimental procedures Microfluidic devices were fabricated in PDMS through a two-layer soft-lithographic process. The human hepatoma cell line HepG2/C3A was cultured within the chip under microfluidic dynamic perfusion (Figure 1, left). Hepatic steatosis was induced using two most common dietary free fatty acids (FFAs), namely Oleic acid (OA) and Palmitic acid (PA) at different molar ratios and 1 mM final concentration for 48h. Que and HT were administered separately, at 10 μM concentration, alone or in combination with the different FFA treatments for 48h. Parameters of hepatic steatosis (i.e., intracellular triglyceride accumulation and related lipotoxicity as well as oxidative stress levels) were evaluated using confocal microscopy-based high‐content analysis. Results and Discussion We found that both polyphenols hamper the progression of the FFA-induced hepatic steatosis showing a cytoprotective effect owing to their lipid-lowering and antioxidant properties (Figure 1, right). Conclusions In this work, we developed an alternative and promising drug screening platform for simulating and investigating the pathogenesis of hepatic steatosis in humans using nutraceuticals as potential therapeutic agents.
A NAFLD-on-a-Chip platform to study the protective effect of natural polyphenols against hepatic steatosis
Manuele Gori
Primo
Writing – Review & Editing
;Pamela Mozetic;Alberto Rainer
2021
Abstract
Introduction Although nonalcoholic fatty liver disease (NAFLD) represents the most common cause of chronic liver disease worldwide, its molecular mechanisms are still under investigation and effective therapies are still far from being available [1]. Two natural polyphenols, Quercetin (Que) and Hydroxytyrosol (HT), are known to have a protective effect against the development of NAFLD and in the reduction of intrahepatic lipogenesis due to their antioxidant and hypolipidemic activities [2,3]. In this work, we leverage a NAFLD-on-a-Chip model to investigate the beneficial effect of the two aforementioned polyphenols on the development of hepatic steatosis, providing novel strategies to contrast the onset and progression of the disease and to face the challenges of drug screening [4]. Experimental procedures Microfluidic devices were fabricated in PDMS through a two-layer soft-lithographic process. The human hepatoma cell line HepG2/C3A was cultured within the chip under microfluidic dynamic perfusion (Figure 1, left). Hepatic steatosis was induced using two most common dietary free fatty acids (FFAs), namely Oleic acid (OA) and Palmitic acid (PA) at different molar ratios and 1 mM final concentration for 48h. Que and HT were administered separately, at 10 μM concentration, alone or in combination with the different FFA treatments for 48h. Parameters of hepatic steatosis (i.e., intracellular triglyceride accumulation and related lipotoxicity as well as oxidative stress levels) were evaluated using confocal microscopy-based high‐content analysis. Results and Discussion We found that both polyphenols hamper the progression of the FFA-induced hepatic steatosis showing a cytoprotective effect owing to their lipid-lowering and antioxidant properties (Figure 1, right). Conclusions In this work, we developed an alternative and promising drug screening platform for simulating and investigating the pathogenesis of hepatic steatosis in humans using nutraceuticals as potential therapeutic agents.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
