Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Review Article
  • Published:

Transcriptional control of metabolism by interferon regulatory factors

Nature Reviews Endocrinology (2024)Cite this article

Subjects

Abstract

Interferon regulatory factors (IRFs) comprise a family of nine transcription factors in mammals. IRFs exert broad effects on almost all aspects of immunity but are best known for their role in the antiviral response. Over the past two decades, IRFs have been implicated in metabolic physiology and pathophysiology, partly as a result of their known functions in immune cells, but also because of direct actions in adipocytes, hepatocytes, myocytes and neurons. This Review focuses predominantly on IRF3 and IRF4, which have been the subject of the most intense investigation in this area. IRF3 is located in the cytosol and undergoes activation and nuclear translocation in response to various signals, including stimulation of Toll-like receptors, RIG-I-like receptors and the cGAS–STING pathways. IRF3 promotes weight gain, primarily by inhibiting adipose thermogenesis, and also induces inflammation and insulin resistance using both weight-dependent and weight-independent mechanisms. IRF4, meanwhile, is generally pro-thermogenic and anti-inflammatory and has profound effects on lipogenesis and lipolysis. Finally, new data are emerging on the role of other IRF family members in metabolic homeostasis. Taken together, data indicate that IRFs serve as critical yet underappreciated integrators of metabolic and inflammatory stress.

Key points

  • Interferon regulatory factors (IRFs) comprise a family of nine transcription factors that evolved coincident with the development of multicellularity in animals and serve to integrate the response to stress, most notably related to infection and inflammation.

  • IRFs help to coordinate metabolic physiology and mediate key aspects of metabolic pathophysiology in diseases such as obesity, type 2 diabetes mellitus and metabolic-associated steatotic liver disease.

  • There is increasing awareness that IRFs not only affect metabolism through their effects on immune cells but also by altering transcription in parenchymal cells such as adipocytes, hepatocytes, myocytes and neurons.

  • IRF3 is generally pro-inflammatory and promotes obesity, insulin resistance, and hepatic steatosis and might also mediate some of the transcriptional actions of leptin in the hypothalamus.

  • IRF4 is generally anti-inflammatory and has essential roles in adipogenesis, lipolysis and thermogenesis in adipose tissue.

  • Other IRFs are beginning to be implicated in metabolic homeostasis, and more insights are likely to emerge over the next few years.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Fig. 1: The structure of IRF family members.
Fig. 2: Classic mechanism of IRF3 activation.
Fig. 3: Regulation of adipose insulin sensitivity and thermogenesis by IRF3.
Fig. 4: The effect of IRF3 in hepatocytes.
Fig. 5: IRF4 and adipose thermogenesis.
Fig. 6: Associations between IRF family members and metabolic traits.

Similar content being viewed by others

References

  1. Miyamoto, M. et al. Regulated expression of a gene encoding a nuclear factor, IRF-1, that specifically binds to IFN-β gene regulatory elements. Cell 54, 903–913 (1988).

    Article  CAS  PubMed  Google Scholar 

  2. Nehyba, J., Hrdlickova, R. & Bose, H. R. Dynamic evolution of immune system regulators: the history of the interferon regulatory factor family. Mol. Biol. Evol. 26, 2539–2550 (2009).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  3. Tanaka, N., Kawakami, T. & Taniguchi, T. Recognition DNA sequences of interferon regulatory factor 1 (IRF-1) and IRF-2, regulators of cell growth and the interferon system. Mol. Cell Biol. 13, 4531–4538 (1993).

    CAS  PubMed  PubMed Central  Google Scholar 

  4. Taniguchi, T., Ogasawara, K., Takaoka, A. & Tanaka, N. IRF family of transcription factors as regulators of host defense. Annu. Rev. Immunol. 19, 623–655 (2001).

    Article  CAS  PubMed  Google Scholar 

  5. Chen, W. & Royer, W. E. Jr. Structural insights into interferon regulatory factor activation. Cell Signal. 22, 883–887 (2010).

    Article  CAS  PubMed  Google Scholar 

  6. Negishi, H., Taniguchi, T. & Yanai, H. The interferon (IFN) class of cytokines and the IFN regulatory factor (IRF) transcription factor family. Cold Spring Harb. Perspect. Biol. 10, a028423 (2018).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Zhao, G. N., Jiang, D. S. & Li, H. Interferon regulatory factors: at the crossroads of immunity, metabolism, and disease. Biochim. Biophys. Acta 1852, 365–378 (2015).

    Article  CAS  PubMed  Google Scholar 

  8. Jefferies, C. A. Regulating IRFs in IFN driven disease. Front. Immunol. 10, 325 (2019).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Mogensen, T. H. IRF and STAT transcription factors — from basic biology to roles in infection, protective immunity, and primary immunodeficiencies. Front. Immunol. 9, 3047 (2018).

    Article  CAS  PubMed  Google Scholar 

  10. Yanai, H., Negishi, H. & Taniguchi, T. The IRF family of transcription factors: inception, impact and implications in oncogenesis. Oncoimmunology 1, 1376–1386 (2012).

    Article  PubMed  PubMed Central  Google Scholar 

  11. Yu, L., Wang, L. & Chen, S. Endogenous Toll-like receptor ligands and their biological significance. J. Cell Mol. Med. 14, 2592–2603 (2010).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Alexopoulou, L., Holt, A. C., Medzhitov, R. & Flavell, R. A. Recognition of double-stranded RNA and activation of NF-κB by Toll-like receptor 3. Nature 413, 732–738 (2001).

    Article  CAS  PubMed  Google Scholar 

  13. Kariko, K., Ni, H., Capodici, J., Lamphier, M. & Weissman, D. mRNA is an endogenous ligand for Toll-like receptor 3. J. Biol. Chem. 279, 12542–12550 (2004).

    Article  CAS  PubMed  Google Scholar 

  14. Bernard, J. J. et al. Ultraviolet radiation damages self noncoding RNA and is detected by TLR3. Nat. Med. 18, 1286–1290 (2012).

    Article  CAS  PubMed  Google Scholar 

  15. Lu, Y. C., Yeh, W. C. & Ohashi, P. S. LPS/TLR4 signal transduction pathway. Cytokine 42, 145–151 (2008).

    Article  CAS  PubMed  Google Scholar 

  16. Termeer, C. et al. Oligosaccharides of hyaluronan activate dendritic cells via toll-like receptor 4. J. Exp. Med. 195, 99–111 (2002).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Lotze, M. T. & Tracey, K. J. High-mobility group box 1 protein (HMGB1): nuclear weapon in the immune arsenal. Nat. Rev. Immunol. 5, 331–342 (2005).

    Article  CAS  PubMed  Google Scholar 

  18. Ohashi, K., Burkart, V., Flohé, S. & Kolb, H. Cutting edge: heat shock protein 60 is a putative endogenous ligand of the toll-like receptor-4 complex. J. Immunol. 164, 558–561 (2000).

    Article  CAS  PubMed  Google Scholar 

  19. Roelofs, M. F. et al. Identification of small heat shock protein B8 (HSP22) as a novel TLR4 ligand and potential involvement in the pathogenesis of rheumatoid arthritis. J. Immunol. 176, 7021–7027 (2006).

    Article  CAS  PubMed  Google Scholar 

  20. Asea, A. et al. Novel signal transduction pathway utilized by extracellular HSP70: role of toll-like receptor (TLR) 2 and TLR4. J. Biol. Chem. 277, 15028–15034 (2002).

    Article  CAS  PubMed  Google Scholar 

  21. Shi, H. et al. TLR4 links innate immunity and fatty acid-induced insulin resistance. J. Clin. Invest. 116, 3015–3025 (2006).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. Mukhopadhyay, S. & Bhattacharya, S. Plasma fetuin-a triggers inflammatory changes in macrophages and adipocytes by acting as an adaptor protein between NEFA and TLR-4. Diabetologia 59, 859–860 (2016).

    Article  PubMed  Google Scholar 

  23. Yang, Y. et al. The emerging role of Toll-like receptor 4 in myocardial inflammation. Cell Death Dis. 7, e2234 (2016).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Kim, J. J. & Sears, D. D. TLR4 and insulin resistance. Gastroenterol. Res. Pract. 2010, 212563 (2010).

    Article  PubMed  PubMed Central  Google Scholar 

  25. Honda, K. & Taniguchi, T. IRFs: master regulators of signalling by Toll-like receptors and cytosolic pattern-recognition receptors. Nat. Rev. Immunol. 6, 644–658 (2006).

    Article  CAS  PubMed  Google Scholar 

  26. Kawai, T. & Akira, S. The role of pattern-recognition receptors in innate immunity: update on Toll-like receptors. Nat. Immunol. 11, 373–384 (2010).

    Article  CAS  PubMed  Google Scholar 

  27. Wang, L., Li, D., Yang, K., Hu, Y. & Zeng, Q. Toll-like receptor-4 and mitogen-activated protein kinase signal system are involved in activation of dendritic cells in patients with acute coronary syndrome. Immunology 125, 122–130 (2008).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Weighardt, H. et al. Identification of a TLR4- and TRIF-dependent activation program of dendritic cells. Eur. J. Immunol. 34, 558–564 (2004).

    Article  CAS  PubMed  Google Scholar 

  29. Fitzgerald, K. A. et al. IKKε and TBK1 are essential components of the IRF3 signaling pathway. Nat. Immunol. 4, 491–496 (2003).

    Article  CAS  PubMed  Google Scholar 

  30. Qin, B. Y. et al. Crystal structure of IRF-3 in complex with CBP. Structure 13, 1269–1277 (2005).

    Article  CAS  PubMed  Google Scholar 

  31. Grandvaux, N. et al. Transcriptional profiling of interferon regulatory factor 3 target genes: direct involvement in the regulation of interferon-stimulated genes. J. Virol. 76, 5532–5539 (2002).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  32. Kumar, K. P., McBride, K. M., Weaver, B. K., Dingwall, C. & Reich, N. C. Regulated nuclear-cytoplasmic localization of interferon regulatory factor 3, a subunit of double-stranded RNA-activated factor 1. Mol. Cell. Biol. 20, 4159–4168 (2000).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  33. Hiscott, J. et al. Triggering the interferon response: the role of IRF-3 transcription factor. J. Interferon Cytokine Res. 19, 1–13 (1999).

    Article  CAS  PubMed  Google Scholar 

  34. Doyle, S. E. et al. IRF3 mediates a TLR3/TLR4-specific antiviral gene program. Immunity 17, 251–263 (2002).

    Article  CAS  PubMed  Google Scholar 

  35. Panne, D., Maniatis, T. & Harrison, S. C. An atomic model of the interferon-β enhanceosome. Cell 129, 1111–1123 (2007).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  36. Yoneyama, M. et al. The RNA helicase RIG-I has an essential function in double-stranded RNA-induced innate antiviral responses. Nat. Immunol. 5, 730–737 (2004).

    Article  CAS  PubMed  Google Scholar 

  37. Yoneyama, M. et al. Shared and unique functions of the DExD/H-box helicases RIG-I, MDA5, and LGP2 in antiviral innate immunity. J. Immunol. 175, 2851–2858 (2005).

    Article  CAS  PubMed  Google Scholar 

  38. Tengroth, L. et al. Functional effects of Toll-like receptor (TLR)3, 7, 9, RIG-I and MDA-5 stimulation in nasal epithelial cells. PLoS One 9, e98239 (2014).

    Article  PubMed  PubMed Central  Google Scholar 

  39. Yoneyama, M. & Fujita, T. RNA recognition and signal transduction by RIG-I-like receptors. Immunol. Rev. 227, 54–65 (2009).

    Article  CAS  PubMed  Google Scholar 

  40. Dixit, E. et al. Peroxisomes are signaling platforms for antiviral innate immunity. Cell 141, 668–681 (2010).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  41. Liu, X. Y., Chen, W., Wei, B., Shan, Y. F. & Wang, C. IFN-induced TPR protein IFIT3 potentiates antiviral signaling by bridging MAVS and TBK1. J. Immunol. 187, 2559–2568 (2011).

    Article  CAS  PubMed  Google Scholar 

  42. Kato, H. et al. Cell type-specific involvement of RIG-I in antiviral response. Immunity 23, 19–28 (2005).

    Article  CAS  PubMed  Google Scholar 

  43. Sun, L., Wu, J., Du, F., Chen, X. & Chen, Z. J. Cyclic GMP-AMP synthase is a cytosolic DNA sensor that activates the type I interferon pathway. Science 339, 786–791 (2013).

    Article  CAS  PubMed  Google Scholar 

  44. Wu, X. et al. Molecular evolutionary and structural analysis of the cytosolic DNA sensor cGAS and STING. Nucleic Acids Res. 42, 8243–8257 (2014).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  45. Li, T. & Chen, Z. J. The cGAS-cGAMP-STING pathway connects DNA damage to inflammation, senescence, and cancer. J. Exp. Med. 215, 1287–1299 (2018).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  46. Chen, Q., Sun, L. & Chen, Z. J. Regulation and function of the cGAS-STING pathway of cytosolic DNA sensing. Nat. Immunol. 17, 1142–1149 (2016).

    Article  CAS  PubMed  Google Scholar 

  47. White, M. J. et al. Apoptotic caspases suppress mtDNA-induced STING-mediated type I IFN production. Cell 159, 1549–1562 (2014).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  48. West, A. P. et al. Mitochondrial DNA stress primes the antiviral innate immune response. Nature 520, 553–557 (2015).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  49. Wu, J. et al. Cyclic GMP-AMP is an endogenous second messenger in innate immune signaling by cytosolic DNA. Science 339, 826–830 (2013).

    Article  CAS  PubMed  Google Scholar 

  50. Reilly, S. M. et al. An inhibitor of the protein kinases TBK1 and IKK-ɛ improves obesity-related metabolic dysfunctions in mice. Nat. Med. 19, 313–321 (2013).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  51. Zhao, P. et al. TBK1 at the crossroads of inflammation and energy homeostasis in adipose tissue. Cell 172, 731–743.e12 (2018).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  52. Hrincius, E. R. et al. Phosphatidylinositol-3-kinase (PI3K) is activated by influenza virus vRNA via the pathogen pattern receptor Rig-I to promote efficient type I interferon production. Cell Microbiol. 13, 1907–1919 (2011).

    Article  CAS  PubMed  Google Scholar 

  53. Joung, S. M. et al. Akt contributes to activation of the TRIF-dependent signaling pathways of TLRs by interacting with TANK-binding kinase 1. J. Immunol. 186, 499–507 (2011).

    Article  CAS  PubMed  Google Scholar 

  54. Sarkar, S. N. et al. Novel roles of TLR3 tyrosine phosphorylation and PI3 kinase in double-stranded RNA signaling. Nat. Struct. Mol. Biol. 11, 1060–1067 (2004).

    Article  CAS  PubMed  Google Scholar 

  55. Yeon, S. H., Song, M. J., Kang, H. R. & Lee, J. Y. Phosphatidylinositol-3-kinase and Akt are required for RIG-I-mediated anti-viral signalling through cross-talk with IPS-1. Immunology 144, 312–320 (2015).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  56. Ren, D. et al. Metformin activates the STING/IRF3/IFN-β pathway by inhibiting AKT phosphorylation in pancreatic cancer. Am. J. Cancer Res. 10, 2851–2864 (2020).

    CAS  PubMed  PubMed Central  Google Scholar 

  57. Xiao, J. et al. Targeting 7-dehydrocholesterol reductase integrates cholesterol metabolism and IRF3 activation to eliminate infection. Immunity 52, 109–122.e6 (2020).

    Article  CAS  PubMed  Google Scholar 

  58. Bluher, M. et al. Activated Ask1-MKK4-p38MAPK/JNK stress signaling pathway in human omental fat tissue may link macrophage infiltration to whole-body Insulin sensitivity. J. Clin. Endocrinol. Metab. 94, 2507–2515 (2009).

    Article  PubMed  Google Scholar 

  59. Lucchini, F. C. et al. ASK1 inhibits browning of white adipose tissue in obesity. Nat. Commun. 11, 1642 (2020).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  60. Yang, S. et al. Metabolic enzyme UAP1 mediates IRF3 pyrophosphorylation to facilitate innate immune response. Mol. Cell 83, 298–313.e8 (2023).

    Article  CAS  PubMed  Google Scholar 

  61. Tian, M. et al. IRF3 prevents colorectal tumorigenesis via inhibiting the nuclear translocation of β-catenin. Nat. Commun. 11, 5762 (2020).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  62. Chattopadhyay, S., Kuzmanovic, T., Zhang, Y., Wetzel, J. L. & Sen, G. C. Ubiquitination of the transcription factor IRF-3 activates RIPA, the apoptotic pathway that protects mice from viral pathogenesis. Immunity 44, 1151–1161 (2016).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  63. Sanz-Garcia, C. et al. The non-transcriptional activity of IRF3 modulates hepatic immune cell populations in acute-on-chronic ethanol administration in mice. J. Hepatol. 70, 974–984 (2019).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  64. Xu, H. et al. Chronic inflammation in fat plays a crucial role in the development of obesity-related insulin resistance. J. Clin. Invest. 112, 1821–1830 (2003).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  65. Weisberg, S. P. et al. Obesity is associated with macrophage accumulation in adipose tissue. J. Clin. Invest. 112, 1796–1808 (2003).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  66. Kawai, T., Autieri, M. V. & Scalia, R. Adipose tissue inflammation and metabolic dysfunction in obesity. Am. J. Physiol. Cell Physiol. 320, C375–C391 (2021).

    Article  CAS  PubMed  Google Scholar 

  67. Rohm, T. V., Meier, D. T., Olefsky, J. M. & Donath, M. Y. Inflammation in obesity, diabetes, and related disorders. Immunity 55, 31–55 (2022).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  68. Cani, P. D. et al. Metabolic endotoxemia initiates obesity and insulin resistance. Diabetes 56, 1761–1772 (2007).

    Article  CAS  PubMed  Google Scholar 

  69. Erridge, C., Attina, T., Spickett, C. M. & Webb, D. J. A high-fat meal induces low-grade endotoxemia: evidence of a novel mechanism of postprandial inflammation. Am. J. Clin. Nutr. 86, 1286–1292 (2007).

    Article  CAS  PubMed  Google Scholar 

  70. Vetrani, C. et al. From gut microbiota through low-grade inflammation to obesity: key players and potential targets. Nutrients 14, 2103 (2022).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  71. Kim, F. et al. Toll-like receptor-4 mediates vascular inflammation and insulin resistance in diet-induced obesity. Circ. Res. 100, 1589–1596 (2007).

    Article  CAS  PubMed  Google Scholar 

  72. Poggi, M. et al. C3H/HeJ mice carrying a Toll-like receptor 4 mutation are protected against the development of insulin resistance in white adipose tissue in response to a high-fat diet. Diabetologia 50, 1267–1276 (2007).

    Article  CAS  PubMed  Google Scholar 

  73. Suganami, T. et al. Attenuation of obesity-induced adipose tissue inflammation in C3H/HeJ mice carrying a Toll-like receptor 4 mutation. Biochem. Biophys. Res. Commun. 354, 45–49 (2007).

    Article  CAS  PubMed  Google Scholar 

  74. Tsukumo, D. M. et al. Loss-of-function mutation in Toll-like receptor 4 prevents diet-induced obesity and insulin resistance. Diabetes 56, 1986–1998 (2007).

    Article  CAS  PubMed  Google Scholar 

  75. Yuzefovych, L. V. et al. Plasma mitochondrial DNA is elevated in obese type 2 diabetes mellitus patients and correlates positively with insulin resistance. PLoS One 14, e0222278 (2019).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  76. Alkhouri, N. et al. Adipocyte apoptosis, a link between obesity, insulin resistance, and hepatic steatosis. J. Biol. Chem. 285, 3428–3438 (2010).

    Article  CAS  PubMed  Google Scholar 

  77. Ballak, D. B. et al. TLR-3 is present in human adipocytes, but its signalling is not required for obesity-induced inflammation in adipose tissue in vivo. PLoS One 10, e0123152 (2015).

    Article  PubMed  PubMed Central  Google Scholar 

  78. Nance, S. A., Muir, L. & Lumeng, C. Adipose tissue macrophages: regulators of adipose tissue immunometabolism during obesity. Mol. Metab. 66, 101642 (2022).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  79. Chavakis, T., Alexaki, V. I. & Ferrante, A. W. Jr Macrophage function in adipose tissue homeostasis and metabolic inflammation. Nat. Immunol. 24, 757–766 (2023).

    Article  CAS  PubMed  Google Scholar 

  80. Chistiakov, D. A., Myasoedova, V. A., Revin, V. V., Orekhov, A. N. & Bobryshev, Y. V. The impact of interferon-regulatory factors to macrophage differentiation and polarization into M1 and M2. Immunobiology 223, 101–111 (2018).

    Article  CAS  PubMed  Google Scholar 

  81. Chechushkov, A. V. et al. Effect of oxidized dextran on cytokine production and activation of IRF3 transcription factor in macrophages from mice of opposite strains with different sensitivity to tuberculosis infection. Bull. Exp. Biol. Med. 164, 738–742 (2018).

    Article  CAS  PubMed  Google Scholar 

  82. Yanai, H. et al. Revisiting the role of IRF3 in inflammation and immunity by conditional and specifically targeted gene ablation in mice. Proc. Natl Acad. Sci. USA 115, 5253–5258 (2018).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  83. Kuroda, M. et al. Interferon regulatory factor 7 mediates obesity-associated MCP-1 transcription. PLoS One 15, e0233390 (2020).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  84. Kanda, H. et al. MCP-1 contributes to macrophage infiltration into adipose tissue, insulin resistance, and hepatic steatosis in obesity. J. Clin. Invest. 116, 1494–1505 (2006).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  85. Takahashi, K. et al. Adiposity elevates plasma MCP-1 levels leading to the increased CD11b-positive monocytes in mice. J. Biol. Chem. 278, 46654–46660 (2003).

    Article  CAS  PubMed  Google Scholar 

  86. Kamei, N. et al. Overexpression of monocyte chemoattractant protein-1 in adipose tissues causes macrophage recruitment and insulin resistance. J. Biol. Chem. 281, 26602–26614 (2006).

    Article  CAS  PubMed  Google Scholar 

  87. Sartipy, P. & Loskutoff, D. J. Monocyte chemoattractant protein 1 in obesity and insulin resistance. Proc. Natl Acad. Sci. USA 100, 7265–7270 (2003).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  88. Kumari, M. et al. IRF3 promotes adipose inflammation and insulin resistance and represses browning. J. Clin. Invest. 126, 2839–2854 (2016).

    Article  PubMed  PubMed Central  Google Scholar 

  89. Yan, S. et al. IRF3 reduces adipose thermogenesis via ISG15-mediated reprogramming of glycolysis. J. Clin. Invest. 131, e144888 (2021).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  90. Mikkelsen, T. S. et al. Comparative epigenomic analysis of murine and human adipogenesis. Cell 143, 156–169 (2010).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  91. Eguchi, J. et al. Interferon regulatory factors are transcriptional regulators of adipogenesis. Cell Metab. 7, 86–94 (2008).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  92. Tang, P. et al. Regulation of adipogenic differentiation and adipose tissue inflammation by interferon regulatory factor 3. Cell Death Differ. 28, 3022–3035 (2021).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  93. Chow, E. K. et al. A role for IRF3-dependent RXRα repression in hepatotoxicity associated with viral infections. J. Exp. Med. 203, 2589–2602 (2006).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  94. Cohen, P. & Kajimura, S. The cellular and functional complexity of thermogenic fat. Nat. Rev. Mol. Cell Biol. 22, 393–409 (2021).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  95. Dulloo, A. G. & Montani, J. P. Body composition, inflammation and thermogenesis in pathways to obesity and the metabolic syndrome: an overview. Obes. Rev. 13, 1–5 (2012).

    Article  PubMed  Google Scholar 

  96. Goto, T. et al. Proinflammatory cytokine interleukin-1β suppresses cold-induced thermogenesis in adipocytes. Cytokine 77, 107–114 (2016).

    Article  CAS  PubMed  Google Scholar 

  97. Sakamoto, T. et al. Inflammation induced by RAW macrophages suppresses UCP1 mRNA induction via ERK activation in 10T1/2 adipocytes. Am. J. Physiol. Cell Physiol. 304, C729–C738 (2013).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  98. Sakamoto, T. et al. Macrophage infiltration into obese adipose tissues suppresses the induction of UCP1 level in mice. Am. J. Physiol. Endocrinol. Metab. 310, E676–E687 (2016).

    Article  PubMed  Google Scholar 

  99. Nisoli, E. et al. Tumor necrosis factor α mediates apoptosis of brown adipocytes and defective brown adipocyte function in obesity. Proc. Natl Acad. Sci. USA 97, 8033–8038 (2000).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  100. Chung, K. J. et al. A self-sustained loop of inflammation-driven inhibition of beige adipogenesis in obesity. Nat. Immunol. 18, 654–664 (2017).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  101. Bae, J. et al. Activation of pattern recognition receptors in brown adipocytes induces inflammation and suppresses uncoupling protein 1 expression and mitochondrial respiration. Am. J. Physiol. Cell Physiol. 306, C918–C930 (2014).

    Article  CAS  PubMed  Google Scholar 

  102. Okla, M. et al. Activation of Toll-like receptor 4 (TLR4) attenuates adaptive thermogenesis via endoplasmic reticulum stress. J. Biol. Chem. 290, 26476–26490 (2015).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  103. Bai, J. et al. Mitochondrial stress-activated cGAS-STING pathway inhibits thermogenic program and contributes to overnutrition-induced obesity in mice. Commun. Biol. 3, 257 (2020).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  104. Eom, J. et al. Intrinsic expression of viperin regulates thermogenesis in adipose tissues. Proc. Natl Acad. Sci. USA 116, 17419–17428 (2019).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  105. Mao, Y. et al. STING-IRF3 triggers endothelial inflammation in response to free fatty acid-induced mitochondrial damage in diet-induced obesity. Arterioscler. Thromb. Vasc. Biol. 37, 920–929 (2017).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  106. Qiao, J. et al. A distinct role of STING in regulating glucose homeostasis through insulin sensitivity and insulin secretion. Proc. Natl Acad. Sci. USA 119, e2101848119 (2022).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  107. Bai, J. et al. DsbA-L prevents obesity-induced inflammation and insulin resistance by suppressing the mtDNA release-activated cGAS-cGAMP-STING pathway. Proc. Natl Acad. Sci. USA 114, 12196–12201 (2017).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  108. Yang, G. et al. RIG-I deficiency promotes obesity-induced insulin resistance. Pharmaceuticals 14, 1178 (2021).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  109. Chiang, S. H. et al. The protein kinase IKKɛ regulates energy balance in obese mice. Cell 138, 961–975 (2009).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  110. Cruz, V. H., Arner, E. N., Wynne, K. W., Scherer, P. E. & Brekken, R. A. Loss of Tbk1 kinase activity protects mice from diet-induced metabolic dysfunction. Mol. Metab. 16, 139–149 (2018).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  111. Oral, E. A. et al. Inhibition of IKKɛ and TBK1 improves glucose control in a subset of patients with type 2 diabetes. Cell Metab. 26, 157–170.e7 (2017).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  112. Yan, S. et al. Inflammation causes insulin resistance via interferon regulatory factor 3 (IRF3)-mediated reduction in FAHFA levels. Preprint at BioRxiv https://doi.org/10.1101/2023.08.08.552481 (2023).

    Article  PubMed  PubMed Central  Google Scholar 

  113. Yore, M. M. et al. Discovery of a class of endogenous mammalian lipids with anti-diabetic and anti-inflammatory effects. Cell 159, 318–332 (2014).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  114. Erikci Ertunc, M. et al. AIG1 and ADTRP are endogenous hydrolases of fatty acid esters of hydroxy fatty acids (FAHFAs) in mice. J. Biol. Chem. 295, 5891–5905 (2020).

    Article  PubMed  PubMed Central  Google Scholar 

  115. You, D., Chul Jung, B., Villivalam, S. D., Lim, H. W. & Kang, S. JMJD8 is a novel molecular nexus between adipocyte-intrinsic inflammation and insulin resistance. Diabetes 71, 43–59 (2021).

    Article  PubMed  PubMed Central  Google Scholar 

  116. Patel, S. J. et al. Hepatic IRF3 fuels dysglycemia in obesity through direct regulation of Ppp2r1b. Sci. Transl. Med. 14, eabh3831 (2022).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  117. Sangodkar, J. et al. All roads lead to PP2A: exploiting the therapeutic potential of this phosphatase. FEBS J. 283, 1004–1024 (2016).

    Article  CAS  PubMed  Google Scholar 

  118. Qiao, J. T. et al. Activation of the STING-IRF3 pathway promotes hepatocyte inflammation, apoptosis and induces metabolic disorders in nonalcoholic fatty liver disease. Metabolism 81, 13–24 (2018).

    Article  CAS  PubMed  Google Scholar 

  119. Liang, H., Hussey, S. E., Sanchez-Avila, A., Tantiwong, P. & Musi, N. Effect of lipopolysaccharide on inflammation and insulin action in human muscle. PLoS One 8, e63983 (2013).

    Article  PubMed  PubMed Central  Google Scholar 

  120. Otero, Y. F. et al. Enhanced glucose transport, but not phosphorylation capacity, ameliorates lipopolysaccharide-induced impairments in insulin-stimulated muscle glucose uptake. Shock 45, 677–685 (2016).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  121. Park, S. J., Garcia Diaz, J., Um, E. & Hahn, Y. S. Major roles of Kupffer cells and macrophages in NAFLD development. Front. Endocrinol. 14, 1150118 (2023).

    Article  Google Scholar 

  122. Blanc, M. et al. The transcription factor STAT-1 couples macrophage synthesis of 25-hydroxycholesterol to the interferon antiviral response. Immunity 38, 106–118 (2013).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  123. Blanc, M. et al. Host defense against viral infection involves interferon mediated down-regulation of sterol biosynthesis. PLoS Biol. 9, e1000598 (2011).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  124. Liu, S. Y. et al. Interferon-inducible cholesterol-25-hydroxylase broadly inhibits viral entry by production of 25-hydroxycholesterol. Immunity 38, 92–105 (2013).

    Article  PubMed  Google Scholar 

  125. Petersen, J. et al. The major cellular sterol regulatory pathway is required for Andes virus infection. PLoS Pathog. 10, e1003911 (2014).

    Article  PubMed  PubMed Central  Google Scholar 

  126. Li, C. et al. 25-Hydroxycholesterol protects host against Zika virus infection and its associated microcephaly in a mouse model. Immunity 46, 446–456 (2017).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  127. Castrillo, A. et al. Crosstalk between LXR and Toll-like receptor signaling mediates bacterial and viral antagonism of cholesterol metabolism. Mol. Cell 12, 805–816 (2003).

    Article  CAS  PubMed  Google Scholar 

  128. Mendoza-Herrera, K. et al. The leptin system and diet: a mini review of the current evidence. Front. Endocrinol. 12, 749050 (2021).

    Article  Google Scholar 

  129. Heyward, F. D. et al. Integrated genomic analysis of AgRP neurons reveals that IRF3 regulates leptin’s hunger-suppressing effects. Preprint at BioRxiv https://doi.org/10.1101/2022.01.03.474708 (2023).

    Article  Google Scholar 

  130. Wong, R. W. J., Ong, J. Z. L., Theardy, M. S. & Sanda, T. IRF4 as an oncogenic master transcription factor. Cancers 14, 4314 (2022).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  131. IRF4 International Consortium et al. A multimorphic mutation in IRF4 causes human autosomal dominant combined immunodeficiency. Sci. Immunol. 8, eade7953 (2023).

    Article  PubMed Central  Google Scholar 

  132. Mittrucker, H. W. et al. Requirement for the transcription factor LSIRF/IRF4 for mature B and T lymphocyte function. Science 275, 540–543 (1997).

    Article  CAS  PubMed  Google Scholar 

  133. Brass, A. L., Kehrli, E., Eisenbeis, C. F., Storb, U. & Singh, H. Pip, a lymphoid-restricted IRF, contains a regulatory domain that is important for autoinhibition and ternary complex formation with the Ets factor PU.1. Genes Dev. 10, 2335–2347 (1996).

    Article  CAS  PubMed  Google Scholar 

  134. Glasmacher, E. et al. A genomic regulatory element that directs assembly and function of immune-specific AP-1-IRF complexes. Science 338, 975–980 (2012).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  135. Matsuyama, T. et al. Molecular cloning of LSIRF, a lymphoid-specific member of the interferon regulatory factor family that binds the interferon-stimulated response element (ISRE). Nucleic Acids Res. 23, 2127–2136 (1995).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  136. Negishi, H. et al. Negative regulation of Toll-like-receptor signaling by IRF-4. Proc. Natl Acad. Sci. USA 102, 15989–15994 (2005).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  137. Cook, S. L., Franke, M. C., Sievert, E. P. & Sciammas, R. A synchronous IRF4-dependent gene regulatory network in B and helper T cells orchestrating the antibody response. Trends Immunol. 41, 614–628 (2020).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  138. Mahnke, J. et al. Interferon regulatory factor 4 controls TH1 cell effector function and metabolism. Sci. Rep. 6, 35521 (2016).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  139. Man, K. et al. The transcription factor IRF4 is essential for TCR affinity-mediated metabolic programming and clonal expansion of T cells. Nat. Immunol. 14, 1155–1165 (2013).

    Article  CAS  PubMed  Google Scholar 

  140. Feuerer, M. et al. Lean, but not obese, fat is enriched for a unique population of regulatory T cells that affect metabolic parameters. Nat. Med. 15, 930–939 (2009).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  141. Spallanzani, R. G. et al. Distinct immunocyte-promoting and adipocyte-generating stromal components coordinate adipose tissue immune and metabolic tenors. Sci. Immunol. 4, eaaw3658 (2019).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  142. Vasanthakumar, A. et al. The transcriptional regulators IRF4, BATF and IL-33 orchestrate development and maintenance of adipose tissue-resident regulatory T cells. Nat. Immunol. 16, 276–285 (2015).

    Article  CAS  PubMed  Google Scholar 

  143. Honma, K. et al. Interferon regulatory factor 4 negatively regulates the production of proinflammatory cytokines by macrophages in response to LPS. Proc. Natl Acad. Sci. USA 102, 16001–16006 (2005).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  144. Huang, S. C. et al. Metabolic reprogramming mediated by the mTORC2-IRF4 signaling axis is essential for macrophage alternative activation. Immunity 45, 817–830 (2016).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  145. Eguchi, J. et al. Interferon regulatory factor 4 regulates obesity-induced inflammation through regulation of adipose tissue macrophage polarization. Diabetes 62, 3394–3403 (2013).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  146. Satoh, T. et al. The Jmjd3-Irf4 axis regulates M2 macrophage polarization and host responses against helminth infection. Nat. Immunol. 11, 936–944 (2010).

    Article  CAS  PubMed  Google Scholar 

  147. El Chartouni, C., Schwarzfischer, L. & Rehli, M. Interleukin-4 induced interferon regulatory factor (Irf) 4 participates in the regulation of alternative macrophage priming. Immunobiology 215, 821–825 (2010).

    Article  CAS  PubMed  Google Scholar 

  148. Eguchi, J. et al. Transcriptional control of adipose lipid handling by IRF4. Cell Metab. 13, 249–259 (2011).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  149. DiPilato, L. M. et al. The role of PDE3B phosphorylation in the inhibition of lipolysis by insulin. Mol. Cell Biol. 35, 2752–2760 (2015).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  150. Cavallari, J. F. et al. Muramyl dipeptide-based postbiotics mitigate obesity-induced insulin resistance via IRF4. Cell Metab. 25, 1063–1074.e3 (2017).

    Article  CAS  PubMed  Google Scholar 

  151. Duggan, B. M., Singh, A. M., Chan, D. Y. & Schertzer, J. D. Postbiotics engage IRF4 in adipocytes to promote sex-dependent changes in blood glucose during obesity. Physiol. Rep. 10, e15439 (2022).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  152. Kong, X. et al. IRF4 is a key thermogenic transcriptional partner of PGC-1α. Cell 158, 69–83 (2014).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  153. Nguyen, K. D. et al. Alternatively activated macrophages produce catecholamines to sustain adaptive thermogenesis. Nature 480, 104–108 (2011).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  154. Qiu, Y. et al. Eosinophils and type 2 cytokine signaling in macrophages orchestrate development of functional beige fat. Cell 157, 1292–1308 (2014).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  155. Wu, S. et al. M2 macrophages independently promote beige adipogenesis via blocking adipocyte Ets1. Nat. Commun. 15, 1646 (2024).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  156. Fischer, K. et al. Alternatively activated macrophages do not synthesize catecholamines or contribute to adipose tissue adaptive thermogenesis. Nat. Med. 23, 623–630 (2017).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  157. Kong, X. et al. Brown adipose tissue controls skeletal muscle function via the secretion of myostatin. Cell Metab. 28, 631–643.e3 (2018).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  158. Zhu, X. et al. IRF4 in skeletal muscle regulates exercise capacity via PTG/glycogen pathway. Adv. Sci. 7, 2001502 (2020).

    Article  CAS  Google Scholar 

  159. Yao, T. et al. Obese skeletal muscle-expressed interferon regulatory factor 4 transcriptionally regulates mitochondrial branched-chain aminotransferase reprogramming metabolome. Diabetes 71, 2256–2271 (2022).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  160. Abdualkader, A. M., Lopaschuk, G. D. & Al Batran, R. The double face of IRF4 in metabolic reprogramming. Diabetes 71, 2251–2252 (2022).

    Article  CAS  PubMed  Google Scholar 

  161. Guo, S. et al. Metabolic crosstalk between skeletal muscle cells and liver through IRF4-FSTL1 in nonalcoholic steatohepatitis. Nat. Commun. 14, 6047 (2023).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  162. Zhao, Y., Wang, X. & Nie, K. IRF1 promotes the chondrogenesis of human adipose-derived stem cells through regulating HILPDA. Tissue Cell 82, 102046 (2023).

    Article  CAS  PubMed  Google Scholar 

  163. Rauch, A. & Mandrup, S. Transcriptional networks controlling stromal cell differentiation. Nat. Rev. Mol. Cell Biol. 22, 465–482 (2021).

    Article  CAS  PubMed  Google Scholar 

  164. Friesen, M. et al. Activation of IRF1 in human adipocytes leads to phenotypes associated with metabolic disease. Stem Cell Rep. 8, 1164–1173 (2017).

    Article  CAS  Google Scholar 

  165. Shin, J. et al. SARS-CoV-2 infection impairs the insulin/IGF signaling pathway in the lung, liver, adipose tissue, and pancreatic cells via IRF1. Metabolism 133, 155236 (2022).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  166. Kissig, M. et al. PRDM16 represses the type I interferon response in adipocytes to promote mitochondrial and thermogenic programing. EMBO J. 36, 1528–1542 (2017).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  167. Cui, H., Banerjee, S., Guo, S., Xie, N. & Liu, G. IFN regulatory factor 2 inhibits expression of glycolytic genes and lipopolysaccharide-induced proinflammatory responses in macrophages. J. Immunol. 200, 3218–3230 (2018).

    Article  CAS  PubMed  Google Scholar 

  168. Sindhu, S. et al. Enhanced adipose expression of interferon regulatory factor (IRF)-5 associates with the signatures of metabolic inflammation in diabetic obese patients. Cells 9, 730 (2020).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  169. Dalmas, E. et al. Irf5 deficiency in macrophages promotes beneficial adipose tissue expansion and insulin sensitivity during obesity. Nat. Med. 21, 610–618 (2015).

    Article  CAS  PubMed  Google Scholar 

  170. Orliaguet, L. et al. Early macrophage response to obesity encompasses interferon regulatory factor 5 regulated mitochondrial architecture remodelling. Nat. Commun. 13, 5089 (2022).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  171. Hedl, M., Yan, J. & Abraham, C. IRF5 and IRF5 disease-risk variants increase glycolysis and human M1 macrophage polarization by regulating proximal signaling and Akt2 activation. Cell Rep. 16, 2442–2455 (2016).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  172. Al-Rashed, F. et al. Repetitive intermittent hyperglycemia drives the M1 polarization and inflammatory responses in THP-1 macrophages through the mechanism involving the TLR4-IRF5 pathway. Cells 9, 1892 (2020).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  173. Gallucci, S., Meka, S. & Gamero, A. M. Abnormalities of the type I interferon signaling pathway in lupus autoimmunity. Cytokine 146, 155633 (2021).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  174. Terrell, M. & Morel, L. The intersection of cellular and systemic metabolism: metabolic syndrome in systemic lupus erythematosus. Endocrinology 163, bqac067 (2022).

    Article  PubMed  PubMed Central  Google Scholar 

  175. Wang, X. A. et al. Interferon regulatory factor 7 deficiency prevents diet-induced obesity and insulin resistance. Am. J. Physiol. Endocrinol. Metab. 305, E485–E495 (2013).

    Article  CAS  PubMed  Google Scholar 

  176. Nodari, A. et al. Interferon regulatory factor 7 impairs cellular metabolism in aging adipose-derived stromal cells. J. Cell Sci. 134, jcs256230 (2021).

    Article  CAS  PubMed  Google Scholar 

  177. Li, Z. et al. IRF7 inhibits the Warburg effect via transcriptional suppression of PKM2 in osteosarcoma. Int. J. Biol. Sci. 18, 30–42 (2022).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  178. Moorman, H. R., Reategui, Y., Poschel, D. B. & Liu, K. IRF8: mechanism of action and health implications. Cells 11, 2630 (2022).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  179. Pearl, D. et al. 4E-BP-dependent translational control of Irf8 mediates adipose tissue macrophage inflammatory response. J. Immunol. 204, 2392–2400 (2020).

    Article  CAS  PubMed  Google Scholar 

  180. Heim, M. H. The Jak-STAT pathway: cytokine signalling from the receptor to the nucleus. J. Recept. Signal. Transduct. Res. 19, 75–120 (1999).

    Article  CAS  PubMed  Google Scholar 

  181. Demiroz, D. et al. Listeria monocytogenes infection rewires host metabolism with regulatory input from type I interferons. PLoS Pathog. 17, e1009697 (2021).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  182. Wang, X. A. et al. Interferon regulatory factor 9 protects against hepatic insulin resistance and steatosis in male mice. Hepatology 58, 603–616 (2013).

    Article  CAS  PubMed  Google Scholar 

  183. Dornbos, P. et al. Evaluating human genetic support for hypothesized metabolic disease genes. Cell Metab. 34, 661–666 (2022).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

Download references

Acknowledgements

The authors thank Suraj Patel (Division of Digestive and Liver Diseases, University of Texas Southwestern School of Medicine) and Sona Kang (Department of Nutritional Sciences and Toxicology, University of California at Berkeley) and the reviewers for a critical reading of the manuscript. E.D.R. is supported by National Institutes of Health awards R01 DK102170 and R01 DK102173.

Author information

Authors and Affiliations

  1. School of Medicine, Royal College of Surgeons in Ireland, Medical University of Bahrain, Busaiteen, Bahrain

    Zunair Ahmad

  2. AdventHealth Orlando Family Medicine, Orlando, FL, USA

    Wahab Kahloan

  3. Division of Endocrinology, Diabetes, and Metabolism, Beth Israel Deaconess Medical Center, Boston, MA, USA

    Evan D. Rosen

  4. Harvard Medical School, Boston, MA, USA

    Evan D. Rosen

Authors
  1. Zunair Ahmad
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Wahab Kahloan
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Evan D. Rosen
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

All authors researched data for the article, contributed substantially to the discussion of content and wrote the manuscript. Z.A. and E.D.R. reviewed and edited the manuscript before submission.

Corresponding author

Correspondence to Evan D. Rosen.

Ethics declarations

Competing interests

The authors declare no competing interests.

Peer review

Peer review information

Nature Reviews Endocrinology thanks Fiachra Humphries, Sander Kersten and the other, anonymous, reviewer(s) for their contribution to the peer review of this work.

Additional information

Publisher’s note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Related links

Genotype-Tissue Expression (GTEx) Portal: https://gtexportal.org/home/

Type 2 Diabetes Knowledge Portal: https://t2d.hugeamp.org/

Rights and permissions

Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Ahmad, Z., Kahloan, W. & Rosen, E.D. Transcriptional control of metabolism by interferon regulatory factors. Nat Rev Endocrinol (2024). https://doi.org/10.1038/s41574-024-00990-0

Download citation

  • Accepted:

  • Published:

  • DOI: https://doi.org/10.1038/s41574-024-00990-0

Search

Advanced search

Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing