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Clinical Research

Evening chronotype is associated with severe NAFLD in obesity

Subjects

Abstract

Background/objectives

Chronotype, i.e., the individual attitude to carry out the daily activities at a certain time of the day, has been reported to play a role in metabolic diseases. Thus, the aim of our study was to investigate the association of non-alcoholic fatty liver disease (NAFLD) with chronotype categories in individuals with obesity.

Subjects/methods

In this cross-sectional study, participants underwent to anthropometric, biochemical, and the Visceral Adiposity Index (VAI) assessment. Chronotype categories were assessed by the Horne–Ostberg Morningness–Eveningness Questionnaire (MEQ). The following indirect indices of NAFLD were calculated: Liver Fat Equation (LFE), Hepatic Steatosis Index (HSI) and Index of Non-alcoholic steatohepatitis (ION).

Results

The study population consisted of 87 participants (40.3 ± 12.3 years; BMI 45.6 ± 6.3 kg/m2; 64F/23M). According to the chronotype score, 31.0% were morning (MC), 36.8% were intermediate (IC), and 32.2% evening chronotype (EC). Individuals with IC were significantly younger than those with MC and EC (p = 0.002 and p = 0.047, respectively). EC presented significantly higher BMI (p < 0.001), waist circumference (p = 0.007), and hip circumference (p = 0.001) than MC. Moreover, EC had higher BMI (p < 0.001) and waist circumference (p = 0.011) than IC. All participants presented NAFLD (HSI ≥ 36 and LFE ≥ 5). Nevertheless, only individuals with EC were above the threshold of non-alcoholic steatohepatitis evaluated as ION index (ION ≥ 50). Individuals with EC presented significantly higher VAI (p = 0.036), LFE (p = 0.034), HSI (p < 0.001) and ION (p = 0.014) than MC, also after the adjustment for age, gender, and BMI.

Conclusion

EC is associated with more severe NAFLD independently of age, gender, and BMI than MC and IC in individuals with obesity.

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Fig. 1: Visceral Adiposity Index and indirect indices of NAFLD according to chronotype categories.

Data availability

The datasets generated during and/or analyzed during the current study are available from the corresponding author on reasonable request.

References

  1. Stenvers DJ, Scheer FAJL, Schrauwen P, la Fleur SE, Kalsbeek A. Circadian clocks and insulin resistance. Nat Rev Endocrinol. 2019;15:75–89. https://doi.org/10.1038/s41574-018-0122-1.

    CAS  Article  PubMed  Google Scholar 

  2. Muscogiuri G, Barrea L, Aprano S, Framondi L, Di Matteo R, Laudisio D, et al. Chronotype and adherence to the Mediterranean diet in obesity: results from the opera prevention project. Nutrients. 2020;12:1354. https://doi.org/10.3390/nu12051354.

    Article  PubMed Central  Google Scholar 

  3. Horne JA, Ostberg O. A self-assessment questionnaire to determine morningness-eveningness in human circadian rhythms. Int J Chronobiol. 1976;4:97–110.

    CAS  PubMed  Google Scholar 

  4. Han H, Dou J, Hou Q, Wang H. Role of circadian rhythm and impact of circadian rhythm disturbance on the metabolism and disease. J Cardiovasc Pharmacol. 2021; https://doi.org/10.1097/FJC.0000000000001178.

  5. Scheer FA, Hilton MF, Mantzoros CS, Shea SA. Adverse metabolic and cardiovascular consequences of circadian misalignment. Proc Natl Acad Sci USA 2009;106:4453–8. https://doi.org/10.1073/pnas.0808180106.

    Article  PubMed  PubMed Central  Google Scholar 

  6. Wong PM, Hasler BP, Kamarck TW, Muldoon MF, Manuck SB. Social jetlag, chronotype, and cardiometabolic risk. J Clin Endocrinol Metab. 2015;100:4612–20. https://doi.org/10.1210/jc.2015-2923.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  7. Barrea L, Vetrani C, Altieri B, Verde L, Savastano S, Colao A, et al. The importance of being a ‘lark’ in post-menopausal women with obesity: a ploy to prevent type 2 diabetes mellitus? Nutrients. 2021;13:3762. https://doi.org/10.3390/nu13113762.

    Article  PubMed  PubMed Central  Google Scholar 

  8. Lotti S, Pagliai G, Colombini B, Sofi F, Dinu M. Chronotype differences in energy intake, cardiometabolic risk parameters, cancer and depression: a systematic review with meta-analysis of observational studies. Adv Nutr. 2021:nmab115. https://doi.org/10.1093/advances/nmab115.

  9. Makarem N, Paul J, Giardina EGV, Liao M, Aggarwal B. Evening chronotype is associated with poor cardiovascular health and adverse health behaviors in a diverse population of women. Chronobiol. Int. 2020;37:673–85. https://doi.org/10.1080/07420528.2020.1732403.

    Article  PubMed  PubMed Central  Google Scholar 

  10. Divella R, Mazzocca A, Daniele A, Sabbà C, Paradiso A. Obesity, nonalcoholic fatty liver disease and adipocytokines network in promotion of cancer. Int J Biol Sci. 2019;15:610–6. https://doi.org/10.7150/ijbs.29599.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  11. Chitturi S, Abeygunasekera S, Farrell GC, Holmes-Walker J, Hui JM, Fung C, et al. NASH and insulin resistance: Insulin hypersecretion and specific association with the insulin resistance syndrome. Hepatology. 2002;35:373–9. https://doi.org/10.1053/jhep.2002.30692.

    CAS  Article  PubMed  Google Scholar 

  12. Wong VW, Hui AY, Tsang SW, Chan JL, Tse AM, Chan KF, et al. Metabolic and adipokine profile of Chinese patients with nonalcoholic fatty liver disease. Clin Gastroenterol Hepatol. 2006;4:1154–61. https://doi.org/10.1016/j.cgh.2006.06.011.

    CAS  Article  PubMed  Google Scholar 

  13. Della Pepa G, Vetrani C, Lombardi G, Bozzetto L, Annuzzi G, Rivellese AA. Isocaloric dietary changes and non-alcoholic fatty liver disease in high cardiometabolic risk individuals. Nutrients. 2017;9:1065. https://doi.org/10.3390/nu9101065.

    CAS  Article  PubMed Central  Google Scholar 

  14. Turek FW, Joshu C, Kohsaka A, Lin E, Ivanova G, McDearmon E, et al. Obesity and metabolic syndrome in circadian Clock mutant mice. Science. 2005;308:1043–5. https://doi.org/10.1126/science.1108750.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  15. Shimba S, Ogawa T, Hitosugi S, Ichihashi Y, Nakadaira Y, Kobayashi M, et al. Deficient of a clock gene, brain and muscle Arnt-like protein-1 (BMAL1), induces dyslipidemia and ectopic fat formation. PLoS One. 2011;6:e25231. https://doi.org/10.1371/journal.pone.0025231.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  16. 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;6:414–21. https://doi.org/10.1016/j.cmet.2007.09.006.

    CAS  Article  PubMed  Google Scholar 

  17. Adamovich Y, Rousso-Noori L, Zwighaft Z, Neufeld-Cohen A, Golik M, Kraut-Cohen J, et al. Circadian clocks and feeding time regulate the oscillations and levels of hepatic triglycerides. Cell Metab. 2014;19:319–30. https://doi.org/10.1016/j.cmet.2013.12.016.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  18. Yu JH, Yun CH, Ahn JH, Suh S, Cho HJ, Lee SK, et al. Evening chronotype is associated with metabolic disorders and body composition in middle-aged adults. J Clin Endocrinol Metab. 2015;100:1494–502. https://doi.org/10.1210/jc.2014-3754.

    CAS  Article  PubMed  Google Scholar 

  19. Muscogiuri G, Barrea L, Aprano S, Framondi L, Di Matteo R, Altieri B, et al. Chronotype and cardio metabolic health in obesity: does nutrition matter? Int J Food Sci Nutr. 2021;72:892–900. https://doi.org/10.1080/09637486.2021.1885017.

    CAS  Article  PubMed  Google Scholar 

  20. Lohman TM, Roche AF, Martorell R. Anthropometric standardization reference manual. Champaign, IL: Human Kinetics; 1988.

  21. Barrea L, Muscogiuri G, Pugliese G, Laudisio D, de Alteriis G, Graziadio C, et al. Phase angle as an easy diagnostic tool of meta-inflammation for the nutritionist. Nutrients. 2021;13:1446. https://doi.org/10.3390/nu13051446.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  22. Madden AM, Smith S. Body composition and morphological assessment of nutritional status in adults: a review of anthropometric variables. J Hum Nutr Diet. 2016;29:7–25. https://doi.org/10.1111/jhn.12278.

    CAS  Article  PubMed  Google Scholar 

  23. Barrea L, Muscogiuri G, Pugliese G, Graziadio C, Maisto M, Pivari F, et al. Association of the chronotype score with circulating trimethylamine N-oxide (TMAO) concentrations. Nutrients. 2021;13:1671. https://doi.org/10.3390/nu13051671.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  24. Della Pepa G, Russo M, Vitale M, Carli F, Vetrani C, Masulli M, et al. Pioglitazone even at low dosage improves NAFLD in type 2 diabetes: clinical and pathophysiological insights from a subgroup of the TOSCA.IT randomised trial. Diabetes Res Clin Pract. 2021;178:108984. https://doi.org/10.1016/j.diabres.2021.108984.

    CAS  Article  PubMed  Google Scholar 

  25. Amato MC, Giordano C, Galia M, Criscimanna A, Vitabile S, Midiri M, et al. Visceral Adiposity Index: a reliable indicator of visceral fat function associated with cardiometabolic risk. Diabetes Care. 2010;33:920–2. https://doi.org/10.2337/dc09-1825.

    Article  PubMed  PubMed Central  Google Scholar 

  26. Kotronen A, Peltonen M, Hakkarainen A, Sevastianova K, Bergholm R, Johansson LM, et al. Prediction of non-alcoholic fatty liver disease and liver fat using metabolic and genetic factors. Gastroenterology. 2009;137:865–72. https://doi.org/10.1053/j.gastro.2009.06.005.

    CAS  Article  PubMed  Google Scholar 

  27. Lee JH, Kim D, Kim HJ, Lee CH, Yang JI, Kim W, et al. Hepatic steatosis index: a simple screening tool reflecting nonalcoholic fatty liver disease. Dig Liver Dis. 2010;42:503–8. https://doi.org/10.1016/j.dld.2009.08.002.

    CAS  Article  PubMed  Google Scholar 

  28. Otgonsuren M, Estep MJ, Hossain N, Younossi E, Frost S, Henry L, et al. Single non-invasive model to diagnose non-alcoholic fatty liver disease (NAFLD) and non-alcoholic steatohepatitis (NASH). J. Gastroenterol Hepatol. 2014;29:2006–13. https://doi.org/10.1111/jgh.12665.

    Article  Google Scholar 

  29. Lakens D. Calculating and reporting effect sizes to facilitate cumulative science: a practical primer for t-tests and ANOVAs. Front Psychol. 2013;4:863. https://doi.org/10.3389/fpsyg.2013.00863.

    Article  PubMed  PubMed Central  Google Scholar 

  30. Ruiz-Lozano T, Vidal J, de Hollanda A, Canteras M, Garaulet M, Izquierdo-Pulido M. Evening chronotype associates with obesity in severely obese subjects: interaction with CLOCK 3111T/C. Int J Obes. 2016;40:1550–7. https://doi.org/10.1038/ijo.2016.116.

    CAS  Article  Google Scholar 

  31. Torres-Castillo N, Martinez-Lopez E, Vizmanos-Lamotte B, Garaulet M. Healthy obese subjects differ in chronotype, sleep habits, and adipose tissue fatty acid composition from their non-healthy counterparts. Nutrients. 2020;13:119. https://doi.org/10.3390/nu13010119.

    CAS  Article  PubMed Central  Google Scholar 

  32. Arora T, Taheri S. Associations among late chronotype, body mass index and dietary behaviors in young adolescents. Int J Obes. 2015;39:39–44. https://doi.org/10.1038/ijo.2014.157.

    CAS  Article  Google Scholar 

  33. Muñoz JSG, Cañavate R, Hernández CM, Cara-Salmerón V, Morante JJH. The association among chronotype, timing of food intake and food preferences depends on body mass status. Eur J Clin Nutr. 2017;71:736–42. https://doi.org/10.1038/ejcn.2016.182.

    Article  PubMed  Google Scholar 

  34. Lucassen EA, Zhao X, Rother KI, Mattingly MS, Courville AB, de Jonge L, et al. Evening chronotype is associated with changes in eating behavior, more sleep apnea, and increased stress hormones in short sleeping obese individuals. PLoS One. 2013;8:e56519. https://doi.org/10.1371/journal.pone.0056519.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  35. Xiao Q, Garaulet M, Scheer FAJL. Meal timing and obesity: interactions with macronutrient intake and chronotype. Int J Obes. 2019;43:1701–11. https://doi.org/10.1038/s41366-018-0284-x.

    Article  Google Scholar 

  36. Maukonen M, Kanerva N, Partonen T, Männistö S. Chronotype and energy intake timing in relation to changes in anthropometrics: a 7-year follow-up study in adults. Chronobiol Int. 2019;36:27–41. https://doi.org/10.1080/07420528.2018.1515772.

    Article  PubMed  Google Scholar 

  37. McMahon DM, Burch JB, Youngstedt SD, Wirth MD, Hardin JW, Hurley TG, et al. Relationships between chronotype, social jetlag, sleep, obesity and blood pressure in healthy young adults. Chronobiol Int. 2019;36:493–509. https://doi.org/10.1080/07420528.2018.1563094.

    Article  PubMed  Google Scholar 

  38. Roenneberg T, Allebrandt KV, Merrow M, Vetter C. Social jetlag and obesity. Curr Biol. 2012;22:939–43. https://doi.org/10.1016/j.cub.2012.03.038.

    CAS  Article  PubMed  Google Scholar 

  39. Parsons MJ, Moffitt TE, Gregory AM, Goldman-Mellor S, Nolan PM, Poulton R, et al. Social jetlag, obesity and metabolic disorder: investigation in a cohort study. Int J Obes. 2015;39:842–8. https://doi.org/10.1038/ijo.2014.201.

    CAS  Article  Google Scholar 

  40. Muscogiuri G, Barrea L, Annunziata G, Di Somma C, Laudisio D, Colao A, et al. Obesity and sleep disturbance: the chicken or the egg? Crit Rev Food Sci Nutr. 2019;59:2158–65. https://doi.org/10.1080/10408398.2018.1506979.

    Article  PubMed  Google Scholar 

  41. Muscogiuri G, Tuccinardi D, Nicastro V, Barrea L, Colao A, Savastano S. Sleep disturbances: one of the culprits of obesity-related cardiovascular risk? Int J Obes Suppl. 2020;10:62–72. https://doi.org/10.1038/s41367-020-0019-z.

    Article  PubMed  PubMed Central  Google Scholar 

  42. Pugliese G, Barrea L, Laudisio D, Salzano C, Aprano S, Colao A, et al. Sleep apnea, obesity, and disturbed glucose homeostasis: epidemiologic evidence, biologic insights, and therapeutic strategies. Curr Obes Rep. 2020;9:30–38. https://doi.org/10.1007/s13679-020-00369-y.

    Article  PubMed  Google Scholar 

  43. Dockray S, Steptoe A. Chronotype and diurnal cortisol profile in working women: differences between work and leisure days. Psychoneuroendocrinology. 2011;36:649–55. https://doi.org/10.1016/j.psyneuen.2010.09.008.

    CAS  Article  PubMed  Google Scholar 

  44. Kudielka BM, Federenko IS, Hellhammer DH, Wüst S. Morningness and eveningness: the free cortisol rise after awakening in “early birds” and “night owls”. Biol Psychol. 2006;72:141–6. https://doi.org/10.1016/j.biopsycho.2005.08.003.

    Article  PubMed  Google Scholar 

  45. Baudrand R, Vaidya A. Cortisol dysregulation in obesity-related metabolic disorders. Curr Opin Endocrinol Diabetes Obes. 2015;22:143–9. https://doi.org/10.1097/MED.0000000000000152.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  46. Abraham SB, Rubino D, Sinaii N, Ramsey S, Nieman LK. Cortisol, obesity, and the metabolic syndrome: a cross-sectional study of obese subjects and review of the literature. Obesity. 2013;21:E105–E117. https://doi.org/10.1002/oby.20083.

    CAS  Article  PubMed  Google Scholar 

  47. Castera L, Friedrich-Rust M, Loomba R. Noninvasive assessment of liver disease in patients with nonalcoholic fatty liver disease. Gastroenterology. 2019;156:1264–.e4. https://doi.org/10.1053/j.gastro.2018.12.036.

    Article  PubMed  Google Scholar 

  48. Hassani Zadeh S, Mansoori A, Hosseinzadeh M. Relationship between dietary patterns and non-alcoholic fatty liver disease: a systematic review and meta-analysis. J Gastroenterol Hepatol. 2021;36:1470–8. https://doi.org/10.1111/jgh.15363.

    Article  PubMed  Google Scholar 

  49. Mir HM, Stepanova M, Afendy H, Cable R, Younossi ZM. Association of sleep disorders with nonalcoholic fatty liver disease (NAFLD): a population-based study. J Clin Exp Hepatol. 2013;3:181–5. https://doi.org/10.1016/j.jceh.2013.06.004.

    Article  PubMed  PubMed Central  Google Scholar 

  50. Woods CP, Hazlehurst JM, Tomlinson JW. Glucocorticoids and non-alcoholic fatty liver disease. J Steroid Biochem Mol Biol. 2015;154:94–103. https://doi.org/10.1016/j.jsbmb.2015.07.020.

    CAS  Article  PubMed  Google Scholar 

  51. Targher G, Bertolini L, Rodella S, Zoppini G, Zenari L, Falezza G. Associations between liver histology and cortisol secretion in subjects with nonalcoholic fatty liver disease. Clin Endocrinol. 2006;64:337–41. https://doi.org/10.1111/j.1365-2265.2006.02466.x.

    CAS  Article  Google Scholar 

  52. Holt HB, Wild SH, Postle AD, Zhang J, Koster G, Umpleby M, et al. Cortisol clearance and associations with insulin sensitivity, body fat and fatty liver in middle-aged men. Diabetologia. 2007;50:1024–32. https://doi.org/10.1007/s00125-007-0629-9.

    CAS  Article  PubMed  Google Scholar 

  53. Mukherji A, Bailey SM, Staels B, Baumert TF. The circadian clock and liver function in health and disease. J Hepatol. 2019;71:200–11. https://doi.org/10.1016/j.jhep.2019.03.020.

    Article  PubMed  Google Scholar 

  54. Ferrante A, Gellerman D, Ay A, Woods KP, Filipowicz AM, Jain K, et al. Diurnal preference predicts phase differences in expression of human peripheral circadian clock genes. J Circadian Rhythms. 2015;13:4. https://doi.org/10.5334/jcr.ae.

    Article  PubMed  PubMed Central  Google Scholar 

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Acknowledgements

The authors thank the study participants.

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CV, LB, and GM were responsible for conceptualization; CV and LB conducted the statistical analysis and wrote the manuscript; LV, GS, AD, and GdA contributed to the methodology, including data collection and data management. SS, AC, and GM provided a critical review of the paper. All authors contributed to the critical review and agreed on the final version of the paper.

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Correspondence to Giovanna Muscogiuri.

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Vetrani, C., Barrea, L., Verde, L. et al. Evening chronotype is associated with severe NAFLD in obesity. Int J Obes (2022). https://doi.org/10.1038/s41366-022-01159-3

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