Open AccessFluoxetine Induces Hepatic Lipid Accumulation Via Both Promotion of the SREBP 1c‐Related Lipogenesis and Reduction of Lipolysis in Primary Mouse Hepatocytes
Author(s) -
Feng XueMin,
Xiong Jing,
Qin Hao,
Liu Wei,
Chen RuiNi,
Shang Wei,
Ning Rui,
Hu Gang,
Yang Jian
Publication year - 2012
Publication title -
cns neuroscience and therapeutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.403
H-Index - 69
eISSN - 1755-5949
pISSN - 1755-5930
DOI - 10.1111/cns.12014
Subject(s) - lipogenesis , lipolysis , fatty acid synthase , lipid metabolism , sterol regulatory element binding protein , endocrinology , medicine , chemistry , biology , sterol , cholesterol , adipose tissue
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 W estern blot. Results Fluoxetine significantly induced the lipid accumulation in primary mouse hepatocytes. Moreover, FLX increased the acetyl‐CoA carboxylase 1 ( ACC 1) and fatty acid synthase ( FAS ) expression, which are important enzymes in lipogenesis. Oppositely, Fluoxetine significantly decreased the carboxylesterase 3 ( CES 3) and carboxylesterase 1 ( CES 1) expression, which are related to lipolysis. Further study demonstrated FLX ‐activated SREBP 1c, which is one of the most important transcription factors conducting coordinated transcriptional regulation of lipogenesis gene such as ACC 1 and FAS . And the increase of lipogenesis gene ( ACC 1) was abolished by SB 203580 but not by pyrrolidine dithiocarbamate ( PDTC ), suggesting through p38‐ MAPK pathway. Conclusion Fluoxetine induces hepatic lipid accumulation via both promotion of the SREBP 1c‐related lipogenesis and reduction of lipolysis in primary mouse hepatocytes.