Acanthoic acid modulates lipogenesis in nonalcoholic fatty liver disease via FXR/LXRs-dependent manner

Autor: Ji-Xing Nan, Hui-Qing Piao, Xin Han, Li-Hua Lian, Zhen-Yu Cui, Jian Song, Ge Wang, Xiu-Xiu Dong, Yan-Ling Wu, Shuang Zheng, Li-Shuang Hou
Rok vydání: 2019
Předmět:
0301 basic medicine
Male
medicine.medical_specialty
Palmitic Acid
Receptors
Cytoplasmic and Nuclear
Toxicology
Diet
High-Fat
Cell Line
Palmitic acid
03 medical and health sciences
chemistry.chemical_compound
Mice
0302 clinical medicine
Non-alcoholic Fatty Liver Disease
Internal medicine
Nonalcoholic fatty liver disease
medicine
Animals
PPAR alpha
Aspartate Aminotransferases
Liver X receptor
Fatty acid synthesis
Triglycerides
Liver X Receptors
Triglyceride
Lipogenesis
Body Weight
Alanine Transaminase
General Medicine
medicine.disease
Mice
Inbred C57BL
030104 developmental biology
Endocrinology
chemistry
Gene Expression Regulation
030220 oncology & carcinogenesis
lipids (amino acids
peptides
and proteins)
Guggulsterone
Farnesoid X receptor
Diterpenes
Sterol Regulatory Element Binding Protein 1
Signal Transduction
Zdroj: Chemico-biological interactions. 311
ISSN: 1872-7786
Popis: Acanthoic acid (AA) is a pimaradiene diterpene isolated from Acanthopanax koreanum Nakai (Araliaceae), with anti-inflammatory and hepatic-protective effects. The present study intended to reveal the effect and mechanism of AA on nonalcoholic fatty liver disease (NAFLD) associated with lipid accumulation by activating Farnesoid X receptor (FXR) and liver X receptors (LXRs) signaling. C57BL/6 mice were received a modified Lieber-DeCarli diet with 71% high-fat (L-D) and treated with AA (20 and 40 mg/kg) or equal volume of saline for 12 weeks. The regulation of AA on lipid accumulation was also detected in pro-steatotic stimulated AML12 cells with palmitic acid (PA). When L-D diet-fed mice were treated with AA, loss in body weight, liver index, and liver lipid droplet were observed along with reduced triglyceride (TG) and serum transaminase. Furthermore, AA decreased sterol regulatory element binding protein 1 (SREBP-1) and target genes expression, regulated PPARα and PPARγ expressions, ameliorated hepatic fibrosis markers, enhanced hepatic FXR and LXR, and regulated AMPK-LKB1 and SIRT1 signaling pathway. Moreover, AA attenuated lipid accumulation via FXR and LXR activation in steatotic AML-12 cells, which was confirmed by guggulsterones (FXR antagonist) or GW3965 (LXR agonist). Activation of FXR and LXR signaling caused by AA might increase AMPK-SIRT1 signaling and then contribute to modulating lipid accumulation and fatty acid synthesis, which suggested that activated FXR-LXR axis by AA represented an effective strategy for relieving NAFLD.
Databáze: OpenAIRE
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