GSK3β inhibition suppresses the hepatic lipid accumulation in Schizothorax prenanti
Glycogen synthase kinase-3β (GSK3β) is a serine/threonine kinase involved in the regulation of embryonic development, glycogen metabolism, protein synthesis, mitosis, and apoptosis. To understand the role of GSK3β in hepatic lipid accumulation of Schizothorax prenanti, we used lithium chloride (LiCl), a GSK3β inhibitor, to inhibit the expression and activity of GSK3β. LiCl increased levels of phosphorylation of GSK3β (Ser9) and decreased the protein level of GSK3β. Plasma TG, TC, and LDL-C levels were greatly decreased after LiCl treatment. Additionally, GSK3β inhibition significantly reduced the levels of hepatic triglyceride (TG) and decreased the expression of lipogenesis-related genes in liver. Interestingly, LiCl decreased levels of phosphorylation of STAT3 (Tyr705), and then inhibited the activity of STAT3. These results indicate that in vivo LiCl treatment, which inhibited GSK3β activity, effectively decreased hepatic lipid accumulation through STAT3 in Schizothorax prenanti.
KeywordsLiCl Hepatic lipid Schizothorax prenanti GSK3β STAT3
L.W. and Y.W. conceived and designed the experiments; X.Z. performed the experiments; L.W. wrote the paper; W. L., L.Z., and S.Y. analyzed the data; and Z.L. and D.C. contributed reagents/materials/analysis tools.
This study was supported by the grants from the National Natural Science Foundation of China (31602148).
Compliance with ethical standards
All research involving animals was conducted according to the Regulations for the Administration of Affairs Concerning Experimental Animals (Ministry of Science and Technology, China, revised in June 2004) and approved by the Institutional Animal Care and Use Committee at the College of Animal Science and Technology, Sichuan Agricultural University, Sichuan, China, under permit No. DKYB20110807.
Conflict of interest
The authors declare that they have no competing interests.
- Banko NS, McAlpine CS, Venegas-Pino DE, Raja P, Shi Y, Khan MI, Werstuck GH (2014) Glycogen synthase kinase 3alpha deficiency attenuates atherosclerosis and hepatic steatosis in high fat diet-fed low density lipoprotein receptor-deficient mice. Am J Pathol 184:3394–3404. https://doi.org/10.1016/j.ajpath.2014.07.028 CrossRefGoogle Scholar
- Carol A, Grimes RSJ (2001) The multifaceted roles of glycogen synthase kinase 3 in cellular signaling. Prog Neurobiol:391–426Google Scholar
- Hinds TD Jr, Burns KA, Hosick PA, McBeth L, Nestor-Kalinoski A, Drummond HA, AlAmodi AA, Hankins MW, vanden Heuvel JP, Stec DE (2016) Biliverdin reductase a attenuates hepatic steatosis by inhibition of glycogen synthase kinase (GSK) 3beta phosphorylation of serine 73 of peroxisome proliferator-activated receptor (PPAR) alpha. J Biol Chem 291:25179–25191. https://doi.org/10.1074/jbc.M116.731703 CrossRefGoogle Scholar
- Liu MY, Zhang LL, Li J, Li Y, Li N, Chen MQ (2015) Characteristics of the cross-sectional vorticity of the natural spawning grounds of Schizothorax prenanti and a vague-set similarity model for ecological restoration. PLoS One 10:e0136724. https://doi.org/10.1371/journal.pone.0136724 CrossRefGoogle Scholar
- Lu KL, Xu WN, Wang LN, Zhang DD, Zhang CN, Liu WB (2014) Hepatic beta-oxidation and regulation of carnitine palmitoyltransferase (CPT) I in blunt snout bream Megalobrama amblycephala fed a high fat diet. PloS one:9. https://doi.org/10.1371/journal.pone.0093135
- Osuga HSNYMA-KAHHJ-i, Gotoda YTFSYIKOKHT, Shun ishibashi aNY (1999) Sterol regulatory element-binding protein-1 as a key transcription factor for nutritional induction of Lipogenic enzyme genes. The Journal of biological chemistryGoogle Scholar
- Ren F, Zhang L, Zhang X, Shi H, Wen T, Bai L, Zheng S, Chen Y, Chen D, Li L, Duan Z (2016) Inhibition of glycogen synthase kinase 3beta promotes autophagy to protect mice from acute liver failure mediated by peroxisome proliferator-activated receptor alpha. Cell Death Dis 7:e2151. https://doi.org/10.1038/cddis.2016.56 CrossRefGoogle Scholar
- Schuringa JJ, Wierenga AT, Kruijer W, Vellenga E (2000) Constitutive Stat3, Tyr705, and Ser727 phosphorylation in acute myeloid leukemia cells caused by the autocrine secretion of interleukin-6. Blood 95:3765–3770Google Scholar
- Wan M, Leavens KF, Hunter RW, Koren S, von Wilamowitz-Moellendorff A, Lu M, Satapati S, Chu Q, Sakamoto K, Burgess SC, Birnbaum MJ (2013) A noncanonical, GSK3-independent pathway controls postprandial hepatic glycogen deposition. Cell Metab 18:99–105. https://doi.org/10.1016/j.cmet.2013.06.001 CrossRefGoogle Scholar
- Wang Y, Hou Y, Zhao L, He Z, Jiang J, Li Z, du Z, Yan T, Wang L (2015b) Multiple alternative splicing and differential expression patterns of the glycogen synthase kinase-3beta (GSK3beta) gene in Schizothorax prenanti comparative biochemistry and physiology. B Biochem Mol Biol 181:1–6. https://doi.org/10.1016/j.cbpb.2014.11.004 CrossRefGoogle Scholar
- Wang L, Wang Y, Meng Y, Zhang C, Di L (2018) GSK3-activated STAT5 regulates expression of SFRPs to modulate adipogenesis FASEB J:fj201701314R https://doi.org/10.1096/fj.201701314R