A Combination of Leucine, Metformin, and Sildenafil Treats Nonalcoholic Fatty Liver Disease and Steatohepatitis in Mice
Joint Authors
Zemel, Michael B.
Bruckbauer, Antje
Banerjee, Jheelam
Fu, Lizhi
Li, Fenfen
Cao, Qiang
Cui, Xin
Wu, Rui
Shi, Hang
Xue, Bingzhong
Source
International Journal of Hepatology
Issue
Vol. 2016, Issue 2016 (31 Dec. 2016), pp.1-16, 16 p.
Publisher
Hindawi Publishing Corporation
Publication Date
2016-11-30
Country of Publication
Egypt
No. of Pages
16
Main Subjects
Abstract EN
Sirt1, AMPK, and eNOS modulate hepatic energy metabolism and inflammation and are key players in the development of NASH.
L-leucine, an allosteric Sirt1 activator, synergizes with low doses of metformin or sildenafil on the AMPK-eNOS-Sirt1 pathway to reverse mild NAFLD in preclinical mouse models.
Here we tested a possible multicomponent synergy to yield greater therapeutic efficacy in NAFLD/NASH.
Liver cells and macrophages or an atherogenic diet induced NASH mouse model was treated with two-way and three-way combinations.
The three-way combination Sild-Met-Leu increased hepatic fatty acid oxidation and reduced lipogenic gene expression and inflammatory marker in vitro.
In mice, Sild-Met-Leu reduced the diet induced increases of ALT, TGFβ, PAI-1, IL1β, and TNFα, hepatic collagen expression, and nearly completely reversed hepatocyte ballooning and triglyceride accumulation, while all two-way combinations had only modest effects.
Therefore, these data provide preclinical evidence for therapeutic efficacy of Sild-Met-Leu in the treatment of NAFLD and NASH.
American Psychological Association (APA)
Bruckbauer, Antje& Banerjee, Jheelam& Fu, Lizhi& Li, Fenfen& Cao, Qiang& Cui, Xin…[et al.]. 2016. A Combination of Leucine, Metformin, and Sildenafil Treats Nonalcoholic Fatty Liver Disease and Steatohepatitis in Mice. International Journal of Hepatology،Vol. 2016, no. 2016, pp.1-16.
https://search.emarefa.net/detail/BIM-1106222
Modern Language Association (MLA)
Bruckbauer, Antje…[et al.]. A Combination of Leucine, Metformin, and Sildenafil Treats Nonalcoholic Fatty Liver Disease and Steatohepatitis in Mice. International Journal of Hepatology No. 2016 (2016), pp.1-16.
https://search.emarefa.net/detail/BIM-1106222
American Medical Association (AMA)
Bruckbauer, Antje& Banerjee, Jheelam& Fu, Lizhi& Li, Fenfen& Cao, Qiang& Cui, Xin…[et al.]. A Combination of Leucine, Metformin, and Sildenafil Treats Nonalcoholic Fatty Liver Disease and Steatohepatitis in Mice. International Journal of Hepatology. 2016. Vol. 2016, no. 2016, pp.1-16.
https://search.emarefa.net/detail/BIM-1106222
Data Type
Journal Articles
Language
English
Notes
Includes bibliographical references
Record ID
BIM-1106222