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Horm Metab Res 2015; 47(04): 259-264
DOI: 10.1055/s-0034-1384569
Endocrine Research
© Georg Thieme Verlag KG Stuttgart · New York

Oleic Acid-Induced Hepatic Steatosis is Coupled with Downregulation of Aquaporin 3 and Upregulation of Aquaporin 9 via Activation of p38 Signaling

L.-y. Gu
1   Department of Gastroenterology, The Second Affiliated Hospital, Chongqing Medical University, Chongqing, China
,
L.-w. Qiu
1   Department of Gastroenterology, The Second Affiliated Hospital, Chongqing Medical University, Chongqing, China
,
X.-f. Chen
1   Department of Gastroenterology, The Second Affiliated Hospital, Chongqing Medical University, Chongqing, China
,
L. Lü
1   Department of Gastroenterology, The Second Affiliated Hospital, Chongqing Medical University, Chongqing, China
,
Z.-c. Mei
1   Department of Gastroenterology, The Second Affiliated Hospital, Chongqing Medical University, Chongqing, China
› Author Affiliations
Further Information

Publication History

received 27 April 2014

accepted 24 June 2014

Publication Date:
08 August 2014 (online)

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Abstract

Excess lipid deposition in hepatocytes is a hallmark feature of nonalcoholic fatty liver disease (NAFLD). The present study was designed to explore the expression and regulation of aquaporin (AQP) 3 and AQP9 in oleic acid-induced hepatic steatosis. HepG2 cells were incubated with oleic acid at different concentrations and time points. Oil-Red-O staining and triglyceride content measurement were done to assess the extent of hepatic steatosis. The expression of AQP3 and AQP9 was assessed using quantitative real-time PCR and Western blot analyses. The mitogen-activated protein kinase (MAPK) pathways involved in the regulation of AQP3 and AQP9 expression were checked. Compared to untreated control cells, oleic acid treatment significantly (p<0.05) induced hepatic steatosis in HepG2 cells in a dose- and time-dependent fashion. Oleic acid-treated cells showed a significant reduction in the AQP3 expression and a concomitant increase in the AQP9 expression. Oleic acid exposure led to enhanced phosphorylation of p38, but not ERK1/2 or JNK MAPK. Pharmacological inhibition of p38 rather than ERK1/2 signaling significantly blocked the regulation of AQP3 and AQP9 expression by oleic acid. Oleic acid-induced hepatic steatosis in HepG2 cells is associated with the coordinated regulation of AQP3 and AQP9 via activation of p38 signaling. These findings warrant functional studies of aquaglyceroporins in NAFLD.

Key words

channel proteins - lipid accumulation - nonalcoholic fatty liver disease - signaling pathway
 

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