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Title: Single administration of recombinant IL-6 restores the gene expression of lipogenic enzymes in liver of fasting IL-6-deficient mice.
Authors: Gavito, A L
Cabello, R
Suarez, J
Serrano, A
Pavón, F J
Vida, M
Romero, M
Pardo, V
Bautista, D
Arrabal, S
Decara, J
Cuesta, A L
Valverde, A M
Rodríguez de Fonseca, F
Baixeras, E
metadata.dc.subject.mesh: Acetyl-CoA Carboxylase
Fatty Acid Synthase, Type I
Gene Expression Regulation, Enzymologic
Hep G2 Cells
Mice, Inbred C57BL
Mice, Knockout
Recombinant Proteins
STAT3 Transcription Factor
Stearoyl-CoA Desaturase
Issue Date: 22-Feb-2016
Abstract: 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.
metadata.dc.identifier.doi: 10.1111/bph.13423
Appears in Collections:Producción 2020

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