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Chronobiology: Influences on Metabolic Syndrome and Cardiovascular Risk

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Abstract

Circadian rhythmicity has been widely studied in the cardiovascular system and has a relevant role in three different areas: heart, vascular smooth muscle, and hemostatic capacity of blood. Metabolic syndrome (MetS) and chronodisruption are also highly interconnected. Epidemiologic studies show that shift workers and short sleepers develop obesity and MetS impairments more frequently. In addition, studies performed in experimental models suggest that the circadian clock genes network plays an important role in mammalian energy balance and demonstrate the implication of the clock genes machinery in MetS. New nutrigenomic studies indicate that genetic variants of the CLOCK gene are highly associated with cardiovascular risk and MetS features. The timing of antihypertensive therapies should be also considered to achieve a nocturnal dip in the pattern of blood pressure. Chronotherapy could also be used in MetS treatment, as the appropriate resetting of the circadian system (ie, “chronoenhancement”) may lead to a reduced incidence of obesity and MetS.

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References

Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance

  1. O’Brien E, Sheridan J, O’Malley K: Dippers and non-dippers. Lancet 1988, 332:397.

    Article  Google Scholar 

  2. Ohkubo T, Hozawa A, Yamaguchi J, et al.: Prognostic signifi cance of the nocturnal decline in blood pressure in individuals with and without high 24-h blood pressure: the Ohasama study. J Hypertens 2002, 20:2183–2189.

    Article  CAS  PubMed  Google Scholar 

  3. • Hermida RC, Ayala DE, Portaluppi F: Circadian variation of blood pressure: the basis for the chronotherapy of hypertension. Adv Drug Deliv Rev 2007, 59:904–922. This article explains the interaction between the circadian system and CVD and the particular role of chronotherapy in this pathology.

    Article  CAS  PubMed  Google Scholar 

  4. Cameron AJ, Shaw JE, Zimmet PZ: The metabolic syndrome: prevalence in worldwide populations. Endocrinol Metab Clin North Am 2004, 33:351–375.

    Article  PubMed  Google Scholar 

  5. Bray GA, Bellanger T: Epidemiology, trends and morbidities of obesity and the metabolic syndrome. Endocrine 2006, 29:109–118.

    Article  CAS  PubMed  Google Scholar 

  6. Grundy SM: Metabolic syndrome: connecting and reconciling cardiovascular and diabetes worlds. J Am Coll Cardiol 2006, 47:1093–1100.

    Article  CAS  PubMed  Google Scholar 

  7. Okcay A, Somers VK, Caples SM: Obstructive sleep apnea and hypertension. J Clin Hypertens (Greenwich) 2008, 10:549–555.

    Article  Google Scholar 

  8. Garaulet M, Madrid JA: Chronobiology, genetics and metabolic syndrom.: Curr Opin Lipidol 2009, 20:127–134.

    Article  CAS  PubMed  Google Scholar 

  9. Guilding C, Piggins HD: Challenging the omnipotence of the suprachiasmatic timekeeper: are circadian oscillators present throughout the mammalian brain?. Eur J Neurosci 2007, 25:3195–3216.

    Article  PubMed  Google Scholar 

  10. Saper CB, Fuller PM: Inducible clocks: living in an unpredictable world. Cold Spring Harb Symp Quant Biol 2007, 72:543–550.

    Article  CAS  PubMed  Google Scholar 

  11. Mendoza J, Pévet P, Challet E: High-fat feeding alters the clock synchronization to light. J Physiol 2008, 586:5901–5910.

    Article  CAS  PubMed  Google Scholar 

  12. Bozek K, Relógio A, Kielbasa SM, et al.: Regulation of clock-controlled genes in mammals. PLoS One 2009, 4:e4882.

    Article  PubMed  CAS  Google Scholar 

  13. Hastings MH, Maywood ES, Reddy AB: Two decades of circadian time. J Neuroendocrinol 2008, 20:812–819.

    Article  CAS  PubMed  Google Scholar 

  14. Young ME, Bray MS: Potential role for peripheral circadian clock dyssynchrony in the pathogenesis of cardiovascular dysfunction. Sleep Med 2007, 8:656–667.

    Article  PubMed  Google Scholar 

  15. Bray MS, Young ME: Diurnal variations in myocardial metabolism. Cardiovasc Res 2008, 79:228–237.

    Article  CAS  PubMed  Google Scholar 

  16. Young ME, McNulty PH, Taegtmeyer H: Adaptation and maladaptation of the heart in diabetes: Part II. Potential mechanisms. Circulation 2002, 105:1861–1870.

    Article  CAS  PubMed  Google Scholar 

  17. Goodwin GW, Taylor CS, Taegtmeyer H: Regulation of energy metabolism of the heart during acute increase in heart work. J Biol Chem 1998, 273:29530–29539.

    Article  CAS  PubMed  Google Scholar 

  18. Young ME: The circadian clock within the heart: potential influence on myocardial gene expression, metabolism, and function. Am J Physiol Heart Circ Physiol 2006, 290:H1–H16.

    Article  CAS  PubMed  Google Scholar 

  19. Hastings MH, Reddy AB, Maywood ES: A clockwork web: circadian timing in brain and periphery, in health and disease. Nat Rev Neurosci 2003, 4:649–661.

    Article  CAS  PubMed  Google Scholar 

  20. Nielsen FS, Hansen HP, Jacobsen P, et al.: Increased sympathetic activity during sleep and nocturnal hypertension in type-2 diabetic patients with diabetic nephropathy. Diabet Med 1999, 16:555–562.

    Article  CAS  PubMed  Google Scholar 

  21. Tofler GH, Brezinski D, Schafer AI, et al.: Concurrent morning increase in platelet aggregability and the risk of myocardial infarction and sudden cardiac death. N Engl J Med 1987, 316:1514–1518.

    Article  CAS  PubMed  Google Scholar 

  22. Kurnik PB: Practical implications of circadian variations in thrombolytic and antithrombotic activities. Cardiol Clin 1996, 14:251–262.

    CAS  PubMed  Google Scholar 

  23. Chrusciel P, Goch A, Banach M, et al.: Circadian changes in the hemostatic system in healthy men and patients with cardiovascular diseases. Med Sci Monit 2009, 15:RA203–RA208.

    Google Scholar 

  24. •• Laposky AD, Bass J, Kohsaka A, et al.: Sleep and circadian rhythms: key components in the regulation of energy metabolism. FEBS Lett 2008, 582:142–151. This is a thorough review in which the authors present evidence for the hypothesis that sleep and circadian rhythms have direct impacts on energy metabolism and represent important mechanisms underlying obesity and diabetes.

    Article  CAS  PubMed  Google Scholar 

  25. Spiegel K, Leproult R, Van Cauter E: Impact of sleep debt on metabolic and endocrine function. Lancet 1999, 354:1435–1439.

    Article  CAS  PubMed  Google Scholar 

  26. Arble DM, Bass J, Laposky AD, et al.: Circadian timing of food intake contributes to weight gain. Obesity (Silver Spring) 2009 (in press).

  27. Turek FW, Joshu C, Kohsaka A, et al.: Obesity and metabolic syndrome in circadian Clock mutant mice. Science 2005, 308:1043–1045.

    Article  CAS  PubMed  Google Scholar 

  28. Ando H, Yanagihara H, Hayashi Y, et al.: Rhythmic messenger ribonucleic acid expression of clock genes and adipocytokines in mouse visceral adipose tissue. Endocrinology 2005, 146:5631–5636.

    Article  CAS  PubMed  Google Scholar 

  29. • García-Prieto MD, Tébar FJ, Nicolás F, et al.: Cortisol secretary pattern and glucocorticoid feedback sensitivity in women from a Mediterranean area: relationship with anthropometric characteristics, dietary intake and plasma fatty acid profile. Clin Endocrinol 2007, 66:185–191. In this article, the authors compare different methods of assessment of cortisol circadian metabolism and demonstrate the association with waist and food-intake pattern in a Mediterranean population.

    Article  CAS  Google Scholar 

  30. Hernandez-Morante JJ, Gomez-Santos C, Milagro F, et al.: Expression of cortisol metabolism-related genes shows circadian rhythmic patterns in human adipose tissue. Int J Obes 2009, 33:473–480.

    Article  CAS  Google Scholar 

  31. Gómez-Santos C, Gómez-Abellán P, Madrid JA, et al.: Circadian rhythm of clock genes in human adipose explants. Obesity (Silver Spring) 2009, 17:1481–1485.

    Article  CAS  Google Scholar 

  32. Zhang EE, Liu AC, Hirota T, et al.: A genome-wide RNAi screen for modifiers of the circadian clock in human cells. Cell 2009, 139:199–210.

    Article  CAS  PubMed  Google Scholar 

  33. Garaulet M, Hernández-Morante JJ, de Heredia FP, et al.: Adiponectin, the controversial hormone. Public Health Nutr 2007, 10:1145–1150.

    Article  PubMed  Google Scholar 

  34. Erren TC, Reiter RJ: Defining chronodisruption. J Pineal Res 2009, 46:245–247.

    Article  CAS  PubMed  Google Scholar 

  35. Turek FW, Joshu C, Kohsaka A, et al.: Obesity and metabolic syndrome in circadian Clock mutant mice. Science 2005, 308:1043–1045.

    Article  CAS  PubMed  Google Scholar 

  36. Gómez-Abellán P, Gómez-Santos C, Madrid JA, et al.: Circadian expression of adiponectin and its receptors in human adipose tissue. Endocrinology 2009 (in press).

  37. Prasai MJ, George JT, Scott EM: Molecular clocks, type 2 diabetes and cardiovascular disease. Diab Vasc Dis Res 2008, 5:89–95.

    Article  PubMed  Google Scholar 

  38. Schoenhard JA, Smith LH, Painter CA, et al.: Regulation of the PAI-1 promoter by circadian clock components: differential activation by BMAL1 and BMAL2. J Mol Cell Cardiol 2003, 35:473–481.

    Article  CAS  PubMed  Google Scholar 

  39. Chong NW, Codd V, Chan D, et al.: Circadian clock genes cause activation of the human PAI-1 gene promoter with 4G/5G allelic preference. FEBS Lett 2006, 580:4469–4472.

    Article  CAS  PubMed  Google Scholar 

  40. Viola AU, James LM, Archer SN, et al.: PER3 polymorphism and cardiac autonomic control: effects of sleep debt and circadian phase. Am J Physiol Heart Circ Physiol 2008, 295:H2156–H2163.

    Article  CAS  PubMed  Google Scholar 

  41. • Sookoian S, Gemma C, Gianotti TF, et al.: Genetic variants of Clock transcription factor are associated with individual susceptibility to obesity. Am J Clin Nutr 2008, 87:1606–1615. The association of Clock polymorphisms and obesity opened a new line of research that will give us new answers to the complexity of the relationship between obesity, chronobiology, and genetics.

    CAS  PubMed  Google Scholar 

  42. Scott EM, Carter AM, Grant PJ: Association between polymorphisms in the Clock gene, obesity and the metabolic syndrome in man. Int J Obes (Lond) 2008, 32:658–662.

    Article  CAS  Google Scholar 

  43. •• Garaulet M, Lee YC, Shen J, et al.: Genetic variants in human CLOCK associate with total energy intake and cytokine sleep factors in overweight subjects (GOLDN population). Eur J Hum Genet 2009 (in press). Clock gene variants are associated for the first time with energy intake and different interleukins are related with sleep quality.

  44. Garaulet M, Lee YC, Shen J, et al.: CLOCK genetic variation and metabolic syndrome risk: modulation by monounsaturated fatty acids. Am J Clin Nutr 2009 (in press).

  45. Garaulet M, Corbalán MD, Madrid JA, et al.: CLOCK gene is implicated in weight reduction in obese patients participating in a dietary programme based in Mediterranean Diet. Int J Obes 2009 (in press).

  46. Beilin LJ, Deacon J, Michael CA, et al.: Diurnal rhythms of blood pressure, plasma renin activity, angiotensin II and catecholamines in normotensive and hypertensive pregnancies. Clin Exp Hypertens 1983, B2:271–293.

    Google Scholar 

  47. Hermida RC, Ayala DE, Mojón A, et al.: Ambulatory blood pressure control with bedtime aspirin administration in subjects with prehypertension. Am J Hypertens 2009, 22:896–903.

    Article  CAS  PubMed  Google Scholar 

  48. Yamamotova A, Papezova H, Vevera J: Normalizing effect of bright light therapy on temperature circadian rhythm in patients with eating disorders. Neuro-endocrinol Lett 2008, 29:168–172.

    PubMed  Google Scholar 

  49. Manber R, Bootzin RR, Acebo C, et al.: The effects of regularizing sleep-wake schedules on daytime sleepiness. Sleep 1996, 19:432–441.

    CAS  PubMed  Google Scholar 

  50. Monteleone P, Tortorella A, Docimo L, et al.: Investigation of 3111T/C polymorphism of the clock gene in obese individuals with or without binge eating disorder: association with higher body mass index. Neurosci Lett 2008, 435:300–333.

    Article  CAS  Google Scholar 

  51. Tortorella A, Monteleone P, Martiadis V, et al.: The 3111T/C polymorphism of the clock gene confers a predisposition to a lifetime lower body weight in patients with anorexia nervosa and bulimia nervosa: a preliminary study. Am J Med Genet B Neuropsychiatr Genet 2007, 144B:992–995.

    Article  CAS  PubMed  Google Scholar 

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Acknowledgment

This work was supported by the Government of Education, Science and Research of Murcia (Project BIO/FFA 07/01-0004), The Spanish Ministry of Education and Science (projects AGL2008-01655/ALI and BFU2007-60658/BFI), and The Institute of Health Carlos III (RETICEF, RD06/0013/0019).

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Garaulet, M., Madrid, J.A. Chronobiology: Influences on Metabolic Syndrome and Cardiovascular Risk. Curr Cardio Risk Rep 4, 15–23 (2010). https://doi.org/10.1007/s12170-009-0074-z

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