@article {17639, title = {Prevention of steatohepatitis by pioglitazone: implication of adiponectin-dependent inhibition of SREBP-1c and inflammation.}, journal = {Journal of Hepatology}, volume = {50}, year = {2009}, month = {2009-03-09 00:00:00}, pages = {489-500}, abstract = {

Background/Aims: Peroxisome proliferator-activated receptor gamma (PPARγ) agonist drugs, like pioglitazone (PGZ),\ are proposed as treatments for steatohepatitis. Their mechanisms of action remain ill-clarified.
Methods: To test the hypothesis that PGZ improves steatohepatitis through adiponectin-dependent stimulation of\ AMPK and/or PPARα, mice lacking adiponectin (Adipo-/-) or the AMPKα1 catalytic subunit (AMPKα1-/-) or wildtype (Wt) mice were fed the methionine and choline deficient (MCD) diet, supplemented or not with PGZ.
Results: In Wt mice, PGZ increased circulating levels of adiponectin and reduced the severity of MCD-induced steatohepatitis but there was no evidence of activation of AMPK or PPARα and their downstream targets. By contrast, PGZcompletely repressed nuclear translocation of SREBP-1c, a key transcription factor for de novo lipogenesis. This effectwas lacking in Adipo-/-\ mice in which PGZ failed to prevent steatohepatitis. Surprisingly, AMPKα1-/-\ mice were resistant to MCD-induced steatohepatitis, a status also associated with repression of SREBP-1c.
Conclusions: The preventive effect of PGZ on MCD-induced steatohepatitis depends on adiponectin pregulation but\ apparently does not involve AMPK or PPARα activation. The inhibition of SREBP-1c and dependent repression of lipogenesis are likely to participate in this effect. The mechanisms by which PGZ and adiponectin control SREBP-1c and\ inflammation remain to be elucidated.

}, keywords = {MCD diet, AMPK, PPARalpha, SREBP-1c, Mouse}, doi = {10.1016/j.jhep.2008.10.027}, url = {http://ac.els-cdn.com/S0168827808007952/1-s2.0-S0168827808007952-main.pdf?_tid=b503ee6a-0ffe-11e3-a8fe-00000aab0f02\&acdnat=1377707418_547e26da92e6393e1150becff01cc129}, author = {da Silva Morais, A. and Lebrun, V. and Abarca-Quinones, J. and Brichard, S. and Hue, L. and Guigas, B. and Viollet, B. and Leclercq, I. A.} }