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O jetlag social provoca esteatose hepática via remodelação circadiana mediada pelo ritmo perturbado de prolactina circulante no metabolismo lipídico hepático

  • role： Contribute equally, First author同等贡献者, 第一作者
  • Affiliation：

    Department of Endocrinology, Endocrine and Metabolic Disease Medical Center, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing 210008, China

    Branch of National Clinical Research Centre for Metabolic Diseases, Nanjing 210008, China

Peng-Zi Zhang12,  
  • role： Contribute equally同等贡献者
  • Affiliation：

    National Key Laboratory for Novel Software Technology and the National Institute of Healthcare Data Science, Nanjing University, Nanjing 210008, China

Ying-Huan Shi3,  
  • role： Contribute equally同等贡献者
  • Affiliation：

    Department of Endocrinology, Endocrine and Metabolic Disease Medical Center, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing 210008, China

    Branch of National Clinical Research Centre for Metabolic Diseases, Nanjing 210008, China

Yu-Xin Guo12,  
  • role： Contribute equally同等贡献者
  • Affiliation：

    National Key Laboratory for Novel Software Technology and the National Institute of Healthcare Data Science, Nanjing University, Nanjing 210008, China

Ya-Yuan Li3,  
  • Affiliation：

    Department of Endocrinology, Endocrine and Metabolic Disease Medical Center, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing 210008, China

    Branch of National Clinical Research Centre for Metabolic Diseases, Nanjing 210008, China

Hong-Li Yin12,  
  • Affiliation：

    Department of Endocrinology, Endocrine and Metabolic Disease Medical Center, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing 210008, China

    Branch of National Clinical Research Centre for Metabolic Diseases, Nanjing 210008, China

Tian-Yu Wu12,  
  • Affiliation：

    Department of Endocrinology, Endocrine and Metabolic Disease Medical Center, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing 210008, China

    Branch of National Clinical Research Centre for Metabolic Diseases, Nanjing 210008, China

Ye Zhu12,  
  • Affiliation：

    Department of Endocrinology, Endocrine and Metabolic Disease Medical Center, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing 210008, China

    Branch of National Clinical Research Centre for Metabolic Diseases, Nanjing 210008, China

Jia-Xuan Jiang12,  
  • role： Corresponding author通信作者
  • Affiliation：

    Department of Endocrinology, Endocrine and Metabolic Disease Medical Center, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing 210008, China

    Branch of National Clinical Research Centre for Metabolic Diseases, Nanjing 210008, China

  • Email：biyan@nju.edu.cn
  • Introduction：* Yan Bi biyan@nju.edu.cn
Yan Bi12*

Resumo

Contexto A prevalência do desalinhamento circadiano, particularmente do jetlag social (SJL), contribui significativamente para a epidemia de distúrbios metabólicos. No entanto, o impacto preciso do SJL no fígado permanece pouco elucidado. Métodos A ritmicidade da prolactina circulante (PRL) foi avaliada em sujeitos com SJL e em camundongos sob SJL. O mecanismo causador do SJL na esteatose hepática foi explorado usando modelo de jetlag em camundongos selvagens e Prl−/−. Ensaio repórter de luciferase, ensaio de deslocamento eletroforético e análise de imunoprecipitação de cromatina foram usados para estudar o mecanismo transcripcional do receptor órfão relacionado ao ácido retinoico α sobre o PRL. RNA-seq no fígado humano e de camundongos, assim como análise circadiana, foram usados para estudar o mecanismo do PRL dessíncronizado associado ao SJL no metabolismo lipídico hepático. O efeito terapêutico da intervenção com PRL em camundongos induzidos por SJL em diferentes pontos temporais foi comparado. Resultados SJL aumenta o risco de doença hepática esteatótica associada à disfunção metabólica (MASLD), mediado pela perturbação da ritmicidade do PRL sérico. Em particular, SJL inibe a transcrição rítmica do PRL na hipófise, levando a níveis dessíncronizados de PRL na circulação. Sob condições de jetlag, a ritmicidade da via de sinalização hepática do PRL foi significativamente atenuada, o que resultou em aumento da lipogênese por meio da inibição das expressões de quinase ativada por mitógeno/ciclina D1 hepática. Notavelmente, o tratamento com PRL no nadir de PRL em camundongos com jetlag reduziu o conteúdo lipídico hepático e os marcadores de lesão hepática em maior grau quando comparado à administração convencional de PRL. Conclusões A via de sinalização hepática de PRL reprogramada com concomitante desregulação do metabolismo lipídico foi o mecanismo causador da esteatose hepática sob SJL, mediada pelo ritmo sérico de PRL desregulado. A restauração do ritmo de PRL pode aliviar eficazmente a esteatose hepática induzida por SJL, fornecendo nova percepção para o tratamento de MASLD.

Palavras-chave

Jetlag social;Prolactina;Ritmo circadiano;Doença hepática esteatótica associada à disfunção metabólica (MASLD)

References

  1. 1..
    Riazi K,Azhari H,Charette JH,Underwood FE,King JA,Afshar EE, et al. The prevalence and incidence of NAFLD worldwide: a systematic review and meta-analysis. Lancet Gastroenterol Hepatol. 2022;7(9):851-61.
  2. 2..
    Mukherji A,Bailey SM,Staels B,Baumert TF. The circadian clock and liver function in health and disease. J Hepatol. 2019;71(1):200-11.
  3. 3..
    Roenneberg T. How can social jetlag affect health? Nat Rev Endocrinol.2023;19(7):383-4.
  4. 4..
    Koopman ADM,Rauh SP,Van T’Riet E,Groeneveld L,Van der Heijden AA,Elders PJ,Dekker JM,Nijpels G,Beulens JW,Rutters F. The association between social jetlag, the metabolic syndrome, and type 2 diabetes mellitus in the general population: the new hoorn study. J Biol Rhythms.2017;32(4):359-68. .
  5. 5..
    De Medeiros Lopes XF,Araujo MFS,Lira NCC,Dantas DS,De Souza JC. Social, biological and behavioral factors associated with social jet lag and sleep duration in university students from a low urbanized city. J Multidis-cip Healthc. 2022;15:11-20.
  6. 6..
    Arab A,Karimi E,Garaulet M,FaJL S. Social jetlag and obesity: a systematic review and meta-analysis. Obes Rev. 2023. .
  7. 7..
    Bouman EJ,Beulens JWJ,Groeneveld L,De Kruijk RS,Schoonmade LJ,Remmelzwaal S, et al. The association between social jetlag and param-eters of metabolic syndrome and type 2 diabetes: a systematic review and meta-analysis. J Sleep Res. 2022;32(3):e13770.
  8. 8..
    Gotlieb N,Moeller J,Kriegsfeld LJ. Circadian control of neuroendo-crine function: implications for health and disease. Curr Opin Physiol.2018;5:133-40.
  9. 9..
    Czura CJ,Tracey KJ. Autonomic neural regulation of immunity. J Intern Med. 2005;257(2):156-66.
  10. 10..
    Deng AF,Wang FX,Wang SC,Zhang YZ,Bai L,Su JC. Bone-organ axes:bidirectional crosstalk. Mil Med Res. 2024;11(1):37.
  11. 11..
    Deutschbein T. Physiology of pituitary hormones. In: Pituitary Tumors. Elsevier; 2021. p. 3–21.
  12. 12..
    Hastings MH,Maywood ES,Brancaccio M. Generation of circa-dian rhythms in the suprachiasmatic nucleus. Nat Rev Neurosci.2018;19(8):453-69.
  13. 13..
    Dimitrov S,Lange T,Benedict C,Nowell MA,Jones SA,Schel-ler J, et al. Sleep enhances IL-6 trans-signaling in humans. FASEB J.2006;20(12):2174-6.
  14. 14..
    Hughey JJ,Hastie T,Butte AJ. ZeitZeiger: supervised learning for high-dimensional data from an oscillatory system. Nucleic Acids Res.2016;44(8):e80.
  15. 15..
    Mortimer T,Welz PS,Benitah SA,Sassone-Corsi P,Koronowski KB. Collecting mouse livers for transcriptome analysis of daily rhythms. STAR Protoc.2021;2(2):100539.
  16. 16..
    Kim YH,Lazar MA. Transcriptional control of circadian rhythms and metabolism: a matter of time and space. Endocr Rev. 2020;41(5):707-32.
  17. 17..
    Eckel-Mahan KL,Patel VR,de Mateo S,Orozco-Solis R,Ceglia NJ,Sahar S, et al. Reprogramming of the circadian clock by nutritional challenge. Cell.2013;155(7):1464-78.
  18. 18..
    Hanse EA,Mashek DG,Becker JR,Solmonson AD,Mullany LK,Mashek MT, et al. Cyclin D1 inhibits hepatic lipogenesis via repression of carbohydrate response element binding protein and hepatocyte nuclear factor 4α. Cell Cycle. 2012;11(14):2681-90.
  19. 19..
    Wu T,Duan Y,Jiang J,Gu T,Zhang P,Bi Y. A century of prolactin: emerging perspectives as a metabolic regulator. Diabetes Metab Res Rev.2024;40(6):e3836.
  20. 20..
    Grattan DR. 60 years of neuroendocrinology: the hypothalamo-prolactin axis. J Endocrinol. 2015;226(2):T101-22.
  21. 21..
    Dobolyi A,Oláh S,Keller D,Kumari R,Fazekas EA,Csikós V, et al. Secretion and function of pituitary prolactin in evolutionary perspective. Front Neurosci. 2020;14:621.
  22. 22..
    Kettner NM,Mayo SA,Hua J,Lee C,Moore DD,Fu L. Circadian dysfunction induces leptin resistance in mice. Cell Metab. 2015;22(3):448-59.
  23. 23..
    Kettner NM,Voicu H,Finegold MJ,Coarfa C,Sreekumar A,Putluri N, et al. Circadian homeostasis of liver metabolism suppresses hepatocarcino-genesis. Cancer Cell. 2016;30(6):909-24.
  24. 24..
    Haraguchi A,Nishimura Y,Fukuzawa M,Kikuchi Y,Tahara Y,Shibata S. Use of a social jetlag-mimicking mouse model to determine the effects of a two-day delayed light- and/or feeding-shift on central and peripheral clock rhythms plus cognitive functioning. Chronobiol Int.2020;38(3):426-42.
  25. 25..
    Yamanaka Y,Honma S,Honma KI. Scheduled exposures to a novel environment with a running-wheel differentially accelerate re-entrain-ment of mice peripheral clocks to new light–dark cycles. Genes Cells.2008;13(5):497-507.
  26. 26..
    Takasu NN,Nakamura TJ,Tokuda IT,Todo T,Block GD,Nakamura W. Recov-ery from age-related infertility under environmental light-dark cycles adjusted to the intrinsic circadian period. Cell Rep. 2015;12(9):1407-13.
  27. 27..
    Zhang-Sun ZY,Xu XZ,Escames G,Lei WR,Zhao L,Zhou YZ, et al. Targeting NR1D1 in organ injury: challenges and prospects. Mil Med Res.2023;10(1):62.
  28. 28..
    Guan D,Lazar MA. Interconnections between circadian clocks and metabolism. J Clin Invest. 2021;131(15):e148278.
  29. 29..
    Wittenbrink N,Ananthasubramaniam B,Münch M,Koller B,Maier B,Weschke C, et al. High-accuracy determination of internal circadian time from a single blood sample. J Clin Invest. 2018;128(9):3826-39.
  30. 30..
    Friedman SL,Neuschwander-Tetri BA,Rinella M,Sanyal AJ. Mecha-nisms of NAFLD development and therapeutic strategies. Nat Med.2018;24(7):908-22.
  31. 31..
    Tseng TH,Wang CJ,Lee YJ,Shao YC,Shen CH,Lee KC, et al. Suppression of the proliferation of Huh7 hepatoma cells involving the downregulation of mutant p53 protein and inactivation of the STAT 3 pathway with ailanthoidol. Int J Mol Sci. 2022;23(9):5102.
  32. 32..
    Zhou X,Ohgaki R,Jin C,Xu M,Okanishi H,Endou H, et al. Inhibition of amino acid transporter LAT1 in cancer cells suppresses G0/G1-S transition by downregulating cyclin D1 via p38 MAPK activation. J Pharmacol Sci.2024;154(3):182-91.
  33. 33..
    Wang M,Chen T,Zheng J,Shen C,He G,Zhang J, et al. The role of CLDN11 in promotion of granulosa cell proliferation in polycystic ovary syndrome via activation of the PI3K-Akt signalling pathway. Sci Rep.2025;15(1):3533.
  34. 34..
    Macotela Y,Triebel J,Clapp C. Time for a new perspective on prolactin in metabolism. Trends Endocrinol Metab. 2020;31(4):276-86.
  35. 35..
    Rana S,Munawar M,Shahid A,Malik M,Ullah H,Fatima W, et al. Deregu-lated expression of circadian clock and clock-controlled cell cycle genes in chronic lymphocytic leukemia. Mol Biol Rep. 2013;41(1):95-103.
  36. 36..
    Tahara Y,Shibata S. Circadian rhythms of liver physiology and disease:experimental and clinical evidence. Nat Rev Gastroenterol Hepatol.2016;13(4):217-26.
  37. 37..
    Gnocchi D,Custodero C,Sabbà C,Mazzocca A. Circadian rhythms: a pos-sible new player in non-alcoholic fatty liver disease pathophysiology. J Mol Med (Berl). 2019;97(6):741-59.
  38. 38..
    Kohsaka A,Laposky AD,Ramsey KM,Estrada C,Joshu C,Kobayashi Y, et al. High-fat diet disrupts behavioral and molecular circadian rhythms in mice. Cell Metab. 2007;6(5):414-21.
  39. 39..
    Szosland K,Pawłowicz P,Lewiński AJNL. Prolactin secretion in polycystic ovary syndrome (PCOS). Neuro Endocrinol Lett. 2015;36(1):53-8.
  40. 40..
    Shao S,Yao Z,Lu J,Song Y,He Z,Yu C, et al. Ablation of prolactin receptor increases hepatic triglyceride accumulation. Biochem Biophys Res Com-mun. 2018;498(3):693-9.

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