RT Journal Article
T1 Single administration of recombinant IL-6 restores the gene expression of lipogenic enzymes in liver of fasting IL-6-deficient mice.
A1 Gavito, A L
A1 Cabello, R
A1 Suarez, J
A1 Serrano, A
A1 Pavon, F J
A1 Vida, M
A1 Romero, M
A1 Pardo, V
A1 Bautista, D
A1 Arrabal, S
A1 Decara, J
A1 Cuesta, A L
A1 Valverde, A M
A1 Rodriguez-de-Fonseca, F
A1 Baixeras, E
K1 Fasting
K1 Fatty Acid Synthase, Type I
K1 Gene Expression Regulation, Enzymologic
K1 Hep G2 Cells
AB Lipogenesis is intimately controlled by hormones and cytokines as well as nutritional conditions. IL-6 participates in the regulation of fatty acid metabolism in the liver. We investigated the role of IL-6 in mediating fasting/re-feeding changes in the expression of hepatic lipogenic enzymes. Gene and protein expression of lipogenic enzymes were examined in livers of wild-type (WT) and IL-6-deficient (IL-6(-/-) ) mice during fasting and re-feeding conditions. Effects of exogenous IL-6 administration on gene expression of these enzymes were evaluated in vivo. The involvement of STAT3 in mediating these IL-6 responses was investigated by using siRNA in human HepG2 cells. During feeding, the up-regulation in the hepatic expression of lipogenic genes presented similar time kinetics in WT and IL-6(-/-) mice. During fasting, expression of lipogenic genes decreased gradually over time in both strains, although the initial drop was more marked in IL-6(-/-) mice. Protein levels of hepatic lipogenic enzymes were lower in IL-6(-/-) than in WT mice at the end of the fasting period. In WT, circulating IL-6 levels paralleled gene expression of hepatic lipogenic enzymes. IL-6 administration in vivo and in vitro showed that IL-6-mediated signalling was associated with the up-regulation of hepatic lipogenic enzyme genes. Moreover, silencing STAT3 in HepG2 cells attenuated IL-6 mediated up-regulation of lipogenic gene transcription levels. IL-6 sustains levels of hepatic lipogenic enzymes during fasting through activation of STAT3. Our findings indicate that clinical use of STAT3-associated signalling cytokines, particularly against steatosis, should be undertaken with caution.
PB John Wiley & Sons
YR 2016
FD 2016-03-04
LK http://hdl.handle.net/10668/9715
UL http://hdl.handle.net/10668/9715
LA en
NO Gavito AL, Cabello R, Suarez J, Serrano A, Pavón FJ, Vida M, et al. Single administration of recombinant IL-6 restores the gene expression of lipogenic enzymes in liver of fasting IL-6-deficient mice. Br J Pharmacol. 2016 Mar;173(6):1070-84
NO The present study was financially supported throughfunding from the National System of Health (Instituto de SaludCarlos III), Red de Trastornos Adictivos UE-FEDER 2012 (RD12/0028); Ministerio de Economía y Competitividad (PI13/02261), Plan Nacional sobre Drogas (049/2009 and 049/2013);Consejería de Economía, Innovación y Ciencia, Junta de Andalucía UE-FEDER (CTS-433); Consejería de Salud y BienestarSocial, Junta Andalucía (TCMR0019, PI0552, PI0228-2013 andPI0823-2012). E. B. is a tenured investigator through the I3SNSProgram of the Andalusian “Progreso y Salud” Foundation,Spain. Juan Suarez, Antonia Serrano, and F. Javier Pavón re-ceived a “Miguel Servet” research contract and grant from theNational System of Health (Instituto de Salud Carlos III), andUE-FEDER (CP12/03109, CP14/00212, CP14/00173 respec-tively). Angela-M Valverde was funded by Ministerio deEconomía y Competitividad, Spain (SAF2012-33283) andCIBERDEM (Instituto de Salud Carlos III).
DS RISalud
RD Sep 27, 2025