Fluoxetine Induces Hepatic Lipid Accumulation Via Both Promotion of the SREBP1c-Related Lipogenesis and Reduction of Lipolysis in Primary Mouse Hepatocytes

Autor: Xue-Min Feng, Hao Qin, Ruini Chen, Gang Hu, Wei Liu, Wei Shang, Rui Ning, Jing Xiong, Jian Yang
Rok vydání: 2012
Předmět:
Male
medicine.medical_specialty
MAP Kinase Signaling System
Lipolysis
Carboxylesterase 1
Gene Expression Regulation
Enzymologic
Mice
chemistry.chemical_compound
Pyrrolidine dithiocarbamate
Acetyltransferases
Fluoxetine
Physiology (medical)
Internal medicine
medicine
Animals
Pharmacology (medical)
RNA
Messenger
fas Receptor
Enzyme Inhibitors
Carboxylesterase 3
Cells
Cultured
Pharmacology
Analysis of Variance
Mice
Inbred ICR
Dose-Response Relationship
Drug
biology
Lipogenesis
Lipid metabolism
Original Articles
Lipid Metabolism
Enzyme Activation
Psychiatry and Mental health
Fatty acid synthase
medicine.anatomical_structure
Endocrinology
chemistry
Hepatocyte
Hepatocytes
biology.protein
Sterol Regulatory Element Binding Protein 1
Carboxylic Ester Hydrolases
Selective Serotonin Reuptake Inhibitors
Zdroj: CNS Neuroscience & Therapeutics. 18:974-980
ISSN: 1755-5930
DOI: 10.1111/cns.12014
Popis: Summary Aims In this study, we investigated the peripheral mechanisms underlying the metabolic side effects of fluoxetine (FLX) by focusing on hepatic lipid metabolism. Methods Primary mouse hepatocytes were prepared from male mice by the two-step perfusion method. The lipid accumulation in primary mouse hepatocytes was analyzed via neutral oil staining. And the lipid metabolism enzymes were determined with RT-PCR and Western blot. Results Fluoxetine significantly induced the lipid accumulation in primary mouse hepatocytes. Moreover, FLX increased the acetyl-CoA carboxylase 1 (ACC1) and fatty acid synthase (FAS) expression, which are important enzymes in lipogenesis. Oppositely, Fluoxetine significantly decreased the carboxylesterase 3 (CES3) and carboxylesterase 1 (CES1) expression, which are related to lipolysis. Further study demonstrated FLX-activated SREBP1c, which is one of the most important transcription factors conducting coordinated transcriptional regulation of lipogenesis gene such as ACC1 and FAS. And the increase of lipogenesis gene (ACC1) was abolished by SB203580 but not by pyrrolidine dithiocarbamate (PDTC), suggesting through p38-MAPK pathway. Conclusion Fluoxetine induces hepatic lipid accumulation via both promotion of the SREBP1c-related lipogenesis and reduction of lipolysis in primary mouse hepatocytes.
Databáze: OpenAIRE
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