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Sökning: onr:"swepub:oai:prod.swepub.kib.ki.se:125737716" > Fasting-induced FGF...

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FältnamnIndikatorerMetadata
00003159naa a2200349 4500
001oai:prod.swepub.kib.ki.se:125737716
003SwePub
008240913s2012 | |||||||||||000 ||eng|
0247 a http://kipublications.ki.se/Default.aspx?queryparsed=id:1257377162 URI
0247 a https://doi.org/10.1210/me.2012-11512 DOI
040 a (SwePub)ki
041 a engb eng
042 9 SwePub
072 7a ref2 swepub-contenttype
072 7a art2 swepub-publicationtype
1001 a Archer, Au Karolinska Institutet4 aut
2451 0a Fasting-induced FGF21 is repressed by LXR activation via recruitment of an HDAC3 corepressor complex in mice
264 1b The Endocrine Society,c 2012
520 a The liver plays a pivotal role in the physiological adaptation to fasting and a better understanding of the metabolic adaptive responses may give hints on new therapeutic strategies to control the metabolic diseases. The liver X receptors (LXRs) are well-established regulators of lipid and glucose metabolism. More recently fibroblast growth factor 21 (FGF21) has emerged as an important regulator of energy homeostasis. We hypothesized that the LXR transcription factors could influence Fgf21 expression, which is induced in response to fasting. Wild-type, LXRα−/−, and LXRβ−/− mice were treated for 3 d with vehicle or the LXR agonist GW3965 and fasted for 12 h prior to the killing of the animals. Interestingly, serum FGF21 levels were induced after fasting, but this increase was blunted when the mice were treated with GW3965 independently of genotypes. Compared with wild-type mice, GW3965-treated LXRα−/− and LXRβ−/− mice showed improved insulin sensitivity and enhanced ketogenic response at fasting. Of note is that during fasting, GW3965 treatment tended to reduce liver triglycerides as opposed to the effect of the agonist in the fed state. The LXR-dependent repression of Fgf21 seems to be mainly mediated by the recruitment of LXRβ onto the Fgf21 promoter upon GW3965 treatment. This repression by LXRβ occurs through the recruitment and stabilization of the repressor complex composed of retinoid-related orphan receptor-α/Rev-Erbα/histone deacetylase 3 onto the Fgf21 promoter. Our data clearly demonstrate that there is a cross talk between the LXR and FGF21 signaling pathways in the adaptive response to fasting.
7001 a Venteclef, N4 aut
7001 a Mode, Au Karolinska Institutet4 aut
7001 a Pedrelli, Mu Karolinska Institutet4 aut
7001 a Gabbi, Cu Karolinska Institutet4 aut
7001 a Clement, K4 aut
7001 a Parini, Pu Karolinska Institutet4 aut
7001 a Gustafsson, JAu Karolinska Institutet4 aut
7001 a Korach-Andre, Mu Karolinska Institutet4 aut
7102 a Karolinska Institutet4 org
7730 t Molecular endocrinology (Baltimore, Md.)d : The Endocrine Societyg 26:12, s. 1980-1990q 26:12<1980-1990x 1944-9917x 0888-8809
8564 u https://academic.oup.com/mend/article-pdf/26/12/1980/8934256/mend1980.pdf
8564 8u http://kipublications.ki.se/Default.aspx?queryparsed=id:125737716
8564 8u https://doi.org/10.1210/me.2012-1151

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