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5205158 
Journal Article 
Attenuation of Palmitic Acid-Induced Lipotoxicity by Chlorogenic Acid through Activation of SIRT1 in Hepatocytes 
Yang, L; Wei, J; Sheng, F; Li, P 
2019 
1 
Molecular Nutrition and Food Research
ISSN: 1613-4125
EISSN: 1613-4133 
63 
14 
e1801432 
English 
31168914 
WOS:000476571400005 
SCOPE: Saturated free fatty acids (FFAs) induce hepatocyte lipotoxicity, wherein oxidative stress-associated mitochondrial dysfunction is mechanistically involved. Chlorogenic acid (CGA), a potent antioxidant and anti-inflammatory compound, protects against high-fat-diet-induced oxidative stress and mitochondrial dysfunction in liver. This study investigates whether CGA protects against FFA-induced hepatocyte lipotoxicity via the regulation of mitochondrial fission/fusion and elucidates its underlying mechanisms.

METHODS AND RESULTS: AML12 cell, a non-transformed hepatocyte cell line, is treated with palmitate. Here, it is shown that CGA prevents palmitate-induced lipotoxicity by activation of SIRT1 regulated mitochondrial morphology. CGA treatment mitigates oxidative stress and mitochondrial dysfunction, as evidenced by a decrease in reactive oxygen species (ROS) production, and an increase in mitochondrial mass and mitochondrial membrane potential. CGA also significantly decreases Bax expression and thereby reduces mitochondria-mediated caspase-dependent apoptosis. Mechanistically, CGA attenuates ROS-induced mitochondrial fragmentation by inhibiting dynamin-related protein 1 (Drp1) and enhancing Mfn2 expression. In contrast, the inhibitory effects of CGA on the generation of mitochondrial ROS and Drp1 are blocked by siRNA knockdown of SIRT1.

CONCLUSION: Collectively, these findings show that supplementation with CGA protects hepatocytes from FFA-induced lipotoxicity through activation of SIRT1, which reverses the oxidative stress and dysfunction of mitochondrial biogenesis directly. 
chlorogenic acid; lipotoxicity; mitochondrial dysfunction; mitochondrial fission; fusion; saturated free fatty acids