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Gene Review

Cx3cl1  -  chemokine (C-X3-C motif) ligand 1

Rattus norvegicus

Synonyms: Acc1, C-X3-C motif chemokine 1, CX3C membrane-anchored chemokine, Cx3c, Fkn, ...
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Disease relevance of Cx3cl1

  • We used a diet-induced rat model of nonalcoholic fatty liver disease (NAFLD) and hepatic insulin resistance to explore the impact of suppressing Acc1, Acc2, or both Acc1 and Acc2 on hepatic lipid levels and insulin sensitivity [1].

High impact information on Cx3cl1

  • Malonyl-CoA, generated by acetyl-CoA carboxylases 1 and 2 (Acc1 and Acc2), is a key regulator of both mitochondrial fatty acid oxidation and fat synthesis [1].
  • Suppression of Acc1 also inhibited lipogenesis whereas Acc2 reduction had no effect on lipogenesis [1].
  • While suppression of Acc1 or Acc2 expression with antisense oligonucleotides (ASOs) increased fat oxidation in rat hepatocytes, suppression of both enzymes with a single ASO was significantly more effective in promoting fat oxidation [1].
  • Plasma ketones were significantly elevated compared with controls in the fed state but not in the fasting state, indicating that lowering Acc1 and -2 expression increases hepatic fat oxidation specifically in the fed state [1].
  • Fractalkine (also known as CX3CL1), a CX3C chemokine, activates and attracts monocytes/macrophages to the site of injury/inflammation [2].

Associations of Cx3cl1 with chemical compounds


Biological context of Cx3cl1

  • Fractalkine (CX3CL1) stimulated by nuclear factor kappaB (NF-kappaB)-dependent inflammatory signals induces aortic smooth muscle cell proliferation through an autocrine pathway [2].
  • These studies suggest that pharmacological inhibition of Acc1 and -2 may be a novel approach in the treatment of NAFLD and hepatic insulin resistance [1].

Anatomical context of Cx3cl1


Other interactions of Cx3cl1

  • Fractalkine (CX3C ligand-1; CX3CL1) is a unique chemokine expressed on the extracellular surface of spinal neurons and spinal sensory afferents [9].
  • CXCL10 and CX3CL1 were significantly upregulated in allografts by day 3 post-transplant as compared to syngeneic grafts suggesting a role for these chemokines in the recruitment of effector cells to allografts [10].


  1. Reversal of diet-induced hepatic steatosis and hepatic insulin resistance by antisense oligonucleotide inhibitors of acetyl-CoA carboxylases 1 and 2. Savage, D.B., Choi, C.S., Samuel, V.T., Liu, Z.X., Zhang, D., Wang, A., Zhang, X.M., Cline, G.W., Yu, X.X., Geisler, J.G., Bhanot, S., Monia, B.P., Shulman, G.I. J. Clin. Invest. (2006) [Pubmed]
  2. Fractalkine (CX3CL1) stimulated by nuclear factor kappaB (NF-kappaB)-dependent inflammatory signals induces aortic smooth muscle cell proliferation through an autocrine pathway. Chandrasekar, B., Mummidi, S., Perla, R.P., Bysani, S., Dulin, N.O., Liu, F., Melby, P.C. Biochem. J. (2003) [Pubmed]
  3. Gonadotropin stimulation of ovarian fractalkine expression and fractalkine augmentation of progesterone biosynthesis by luteinizing granulosa cells. Zhao, P., De, A., Hu, Z., Li, J., Mulders, S.M., Sollewijn Gelpke, M.D., Duan, E.K., Hsueh, A.J. Endocrinology (2008) [Pubmed]
  4. Fractalkine (CX3CL1) and fractalkine receptor (CX3CR1) distribution in spinal cord and dorsal root ganglia under basal and neuropathic pain conditions. Verge, G.M., Milligan, E.D., Maier, S.F., Watkins, L.R., Naeve, G.S., Foster, A.C. Eur. J. Neurosci. (2004) [Pubmed]
  5. An initial investigation of spinal mechanisms underlying pain enhancement induced by fractalkine, a neuronally released chemokine. Milligan, E., Zapata, V., Schoeniger, D., Chacur, M., Green, P., Poole, S., Martin, D., Maier, S.F., Watkins, L.R. Eur. J. Neurosci. (2005) [Pubmed]
  6. Expression of fractalkine in the rat testis: molecular cloning of a novel alternative transcript of its gene that is differentially regulated by pro-inflammatory cytokines. Habasque, C., Satie, A.P., Aubry, F., Jégou, B., Samson, M. Mol. Hum. Reprod. (2003) [Pubmed]
  7. Use of cocultured cell systems to elucidate chemokine-dependent neuronal/microglial interactions: control of microglial activation. Zujovic, V., Taupin, V. Methods (2003) [Pubmed]
  8. A role for proinflammatory cytokines and fractalkine in analgesia, tolerance, and subsequent pain facilitation induced by chronic intrathecal morphine. Johnston, I.N., Milligan, E.D., Wieseler-Frank, J., Frank, M.G., Zapata, V., Campisi, J., Langer, S., Martin, D., Green, P., Fleshner, M., Leinwand, L., Maier, S.F., Watkins, L.R. J. Neurosci. (2004) [Pubmed]
  9. Evidence that exogenous and endogenous fractalkine can induce spinal nociceptive facilitation in rats. Milligan, E.D., Zapata, V., Chacur, M., Schoeniger, D., Biedenkapp, J., O'Connor, K.A., Verge, G.M., Chapman, G., Green, P., Foster, A.C., Naeve, G.S., Maier, S.F., Watkins, L.R. Eur. J. Neurosci. (2004) [Pubmed]
  10. IFN-gamma, produced by NK cells that infiltrate liver allografts early after transplantation, links the innate and adaptive immune responses. Obara, H., Nagasaki, K., Hsieh, C.L., Ogura, Y., Esquivel, C.O., Martinez, O.M., Krams, S.M. American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons. (2005) [Pubmed]
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