Omega-3 polyunsaturated fatty acids protect human hepatoma cells from developing steatosis through FFA4 (GPR120).

Kang, Saeromi; Huang, Jin; Lee, Bo-Kyung; Jung, Young-Suk; Im, Eunok; Koh, Jung-Min; Im, Dong-Soon
Biochimica et biophysica acta
2018Feb ; 1863 ( 2 ) :105-116.
저자 상세정보
Kang, Saeromi - Molecular Inflammation Research Center for Aging Intervention (MRCA) and College of Pharmacy, Pusan National University, Busan 469241, Republic of Korea.
Huang, Jin - Molecular Inflammation Research Center for Aging Intervention (MRCA) and College of Pharmacy, Pusan National University, Busan 469241, Republic of Korea.
Lee, Bo-Kyung - Molecular Inflammation Research Center for Aging Intervention (MRCA) and College of Pharmacy, Pusan National University, Busan 469241, Republic of Korea.
Jung, Young-Suk - Molecular Inflammation Research Center for Aging Intervention (MRCA) and College of Pharmacy, Pusan National University, Busan 469241, Republic of Korea.
Im, Eunok - Molecular Inflammation Research Center for Aging Intervention (MRCA) and College of Pharmacy, Pusan National University, Busan 469241, Republic of Korea.
Koh, Jung-Min - Division of Endocrinology and Metabolism, Asan Medical Center, University of Ulsan College of Medicine, Seoul 05505, Republic of Korea.
Im, Dong-Soon - Molecular Inflammation Research Center for Aging Intervention (MRCA) and College of Pharmacy, Pusan National University, Busan 469241, Republic of Korea. Electronic address imds@pusan.ac.kr.
ABSTRACT
Protective effect of omega-3 polyunsaturated fatty acids (n-3 PUFA) on non-alcoholic fatty liver disease has been demonstrated. FFA4 (also known as GPR120; a G protein-coupled receptor) has been suggested to be a target of n-3 PUFA. FFA4 expression in hepatocytes has also been reported from liver biopsies in child fatty liver patients. In order to assess the functional role of FFA4 in hepatic steatosis, we used an in vitro model of liver X receptor (LXR)-mediated hepatocellular steatosis. FFA4 expression was confirmed in Hep3B and HepG2 human hepatoma cells. T0901317 (a specific LXR activator) induced lipid accumulation and docosahexaenoic acid (DHA; a representative n-3 PUFA) inhibited lipid accumulation. This DHA-induced inhibition was blunted by treatment of AH7614 (a FFA4 antagonist) and by transfection of FFA4 siRNA. SREBP-1c (a key transcription factor of lipogenesis) was induced by treatment with T0901317, and SREBP-1c induction was also inhibited by DHA at mRNA and protein levels. DHA-induced suppression of SREBP-1c expression was also blunted by FFA4-knockdown. Furthermore, DHA inhibited T0901317-induced lipid accumulation in primary hepatocytes from wild type mice, but not in those from FFA4 deficient mice. In addition, DHA-induced activations of G(q/11) proteins, CaMKK, and AMPK were found to be signaling components of the steatosis protective pathway. The results of this study suggest that n-3 PUFA protect hepatic steatosis by activating FFA4 in hepatocytes, and its signaling cascade sequentially involves FFA4, G(q/11) proteins, CaMKK, AMPK, and SREBP-1c suppression. CI - Copyright ??2017 Elsevier B.V. All rights reserved.
keyword
*Docosahexaenoic acid; *FFA4; *Hepatocytes; *Liver; *N-3 PUFA; *Steatosis
MESH
AMP-Activated Protein Kinases/genetics/metabolism, Animals, Calcium-Calmodulin-Dependent Protein Kinase Kinase/genetics/metabolism, Carcinoma, Hepatocellular/genetics/*metabolism/pathology, Docosahexaenoic Acids/*pharmacology, Fatty Liver/genetics/metabolism/pathology/*prevention & control, Gene Knockdown Techniques, Hep G2 Cells, Humans, Hydrocarbons, Fluorinated/pharmacology, Liver Neoplasms/genetics/*metabolism/pathology, Mice, Mice, Knockout, Neoplasm Proteins/genetics/*metabolism, Receptors, G-Protein-Coupled/genetics/*metabolism, Sterol Regulatory Element Binding Protein 1/genetics/metabolism, Sulfonamides/pharmacology
링크

주제코드
주제명(Target field)
연구대상(Population)
연구참여(Sample size)
대상성별(Gender)
질병특성(Condition Category)
연구환경(Setting)
연구설계(Study Design)
연구기간(Period)
중재방법(Intervention Type)
중재명칭(Intervention Name)
키워드(Keyword)
유효성결과(Recomendation)
n-3 PUFA protect hepatic steatosis by activating FFA4 in hepatocytes, and its signaling cascade sequentially involves FFA4, Gq/11 proteins, CaMKK, AMPK, and SREBP-1c suppression.
연구비지원(Fund Source)
근거수준평가(Evidence Hierarchy)
출판년도(Year)
참여저자수(Authors)
대표저자
DOI
10.1016/j.bbalip.2017.11.002
KCD코드
ICD 03
건강보험코드