Salsalate and adiponectin improve palmitate-induced insulin resistance via inhibition of selenoprotein P through the AMPK-FOXO1α pathway

Program: Abstracts - Orals, Featured Poster Presentations, and Posters
Session: MON 842-862-Insulin Signaling & Action
Basic/Translational
Monday, June 17, 2013: 1:45 PM-3:45 PM
Expo Halls ABC (Moscone Center)

Poster Board MON-855
Ho Cheol Hong*, Tae Woo Jung, So Young Lee, Hae Yoon Choi, Jae Hee Ahn, Yoon Jung Kim, Nam Hoon Kim, Hye Jin Yoo, Hee Young Kim, Ji A Seo, Nan Hee Kim, Sin Gon Kim, Sei Hyun Baik, Dong Seop Choi and Kyung Mook Choi
College of Medicine, Korea University, Seoul, South Korea
OBJECTIVE―Selenoprotein P (SeP) was recently identified as a hepatokine that induces insulin resistance (IR) in rodents and humans. Randomized clinical trials have shown that salsalate, a prodrug of salicylate, significantly lowers blood glucose levels and increases adiponectin concentrations. We examined the effects of salsalate and adiponectin on the hepatic expression of SeP under hyperlipidemic conditions and explored their regulatory mechanism on SeP.

RESEARCH DESIGN AND METHODS―In palmitate-treated HepG2 cells as well as high fat diet (HFD)-fed SD rats and db/db mice, hepatic SeP expression and its regulatory pathway, including AMPK-FOXO1α, were evaluated after the administration of salsalate and salicylate.

RESULTS―Palmitate treatment significantly increased SeP expression and induced IR, while knock-down of SeP by siRNA restored these changes in HepG2 cells. Palmitate-induced SeP expression was inhibited by both salsalate and salicylate in dose- and time-dependent manners, which was found to be mediated by AMPK-FOXO1α pathway. Moreover, adiponectin were also able to suppress palmitate-induced SeP through the activation of AMPK and improve IR. Salsalate and salicylate treatment improved glucose intolerance and IR, accompanied by reduced SeP mRNA and protein expression in HFD-fed rats and db/db mice, respectively.

CONCLUSION―Salsalate and adiponectin ameliorated palmitate-induced IR in hepatocytes via SeP inhibition through the AMPK-FOXO1α pathway.

Nothing to Disclose: HCH, TWJ, SYL, HYC, JHA, YJK, NHK, HJY, HYK, JAS, NHK, SGK, SHB, DSC, KMC

*Please take note of The Endocrine Society's News Embargo Policy at http://www.endo-society.org/endo2013/media.cfm