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Attenuation of Palmitic Acid–Induced Lipotoxicity by Chlorogenic Acid through Activation of SIRT1 in Hepatocytes
Yang,Lele; Wei,Jinchao; Sheng,Feiya; Li,Peng
2019-07-01
Source PublicationMolecular Nutrition and Food Research
ISSN1613-4125
Volume63Issue:14
Abstract

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.

KeywordChlorogenic Acid Lipotoxicity Mitochondrial Dysfunction Mitochondrial Fission/fusion Saturated Free Fatty Acids
DOI10.1002/mnfr.201801432
URLView the original
Indexed BySCIE
WOS Research AreaFood Science & Technology
WOS SubjectFood Science & Technology
WOS IDWOS:000476571400005
Scopus ID2-s2.0-85067409304
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Cited Times [WOS]:10   [WOS Record]     [Related Records in WOS]
Document TypeJournal article
CollectionInstitute of Chinese Medical Sciences
Corresponding AuthorLi,Peng
AffiliationState Key Laboratory of Quality Research in Chinese Medicine,Institute of Chinese Medical Sciences,University of Macau,999078,Macao
First Author AffilicationInstitute of Chinese Medical Sciences
Corresponding Author AffilicationInstitute of Chinese Medical Sciences
Recommended Citation
GB/T 7714
Yang,Lele,Wei,Jinchao,Sheng,Feiya,et al. Attenuation of Palmitic Acid–Induced Lipotoxicity by Chlorogenic Acid through Activation of SIRT1 in Hepatocytes[J]. Molecular Nutrition and Food Research,2019,63(14).
APA Yang,Lele,Wei,Jinchao,Sheng,Feiya,&Li,Peng.(2019).Attenuation of Palmitic Acid–Induced Lipotoxicity by Chlorogenic Acid through Activation of SIRT1 in Hepatocytes.Molecular Nutrition and Food Research,63(14).
MLA Yang,Lele,et al."Attenuation of Palmitic Acid–Induced Lipotoxicity by Chlorogenic Acid through Activation of SIRT1 in Hepatocytes".Molecular Nutrition and Food Research 63.14(2019).
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