open access

Vol 58, No 3 (2020)
Original paper
Submitted: 2020-02-03
Accepted: 2020-09-13
Published online: 2020-09-22
Get Citation

The Light/Dark cycle disruption affects hepatic function both in metabolic parameters and tissue structure in a nocturnal desert rodent: Gerbillus tarabuli

Amina Derbouz Rouibate12, Nadir Benhafri12, Saliha Ouali-Hassenaoui1, Aicha Dekar-Madoui1
DOI: 10.5603/FHC.a2020.0021
·
Pubmed: 32960973
·
Folia Histochem Cytobiol 2020;58(3):182-197.
Affiliations
  1. USTHB, Faculty of Biological Sciences, Laboratory of Biology and Physiology of Organisms, Neurobiology Team, USTHB, BP 32, El Alia, Bab Ezzouar, 16111 Algiers, Algeria
  2. Dr Yahia Fares University of Medea, Faculty of Sciences, 26000 medea, Algeria

open access

Vol 58, No 3 (2020)
ORIGINAL PAPERS
Submitted: 2020-02-03
Accepted: 2020-09-13
Published online: 2020-09-22

Abstract

Introduction. Biological rhythms, such as Light/Dark (LD) cycles, are an integral component of virtually all aspects of life. These rhythms are controlled in large part by circadian clocks, allowing the organism to adapt its internal rhythmic metabolism to changes in the external environment created by daily fluctuations in the LD cycle. Therefore, changes in the daily duration of the lighting could lead to adverse health consequences. The aim of the study was to investigate, in a nocturnal desert rodent, Gerbillus tarabuli, the effects of the LD cycle disruption on the structure of the hepatic tissue and the content of carbohydrate and lipid parameters as indicators of metabolic state. Material and methods. The present study was conducted on two gerbil groups: control group was exposed to a standard lighting cycle (LD: 12:12), and the shifted group was subjected to a chronic disrupted LD cycle, alternating a standard cycle (LD: 12:12) with a modified cycle (LD: 20:4), i.e., the light phase of 24-h cycle was prolonged by 8 h on every second day during a period of 12 weeks. We used: (i) routine histology and histochemical staining for tissue analysis; (ii) immunohistochemistry (IHC) for MPO detection; (iii) biochemical methods for hepatic glycogen and lipids extraction and quantification. Blood metabolic parameters were assessed by enzymatic methods. Results. Our structural results indicate in the shifted group an alteration of tissue architecture, showing widely scattered inflammatory foci with many dilated sinusoids and prominent leukocyte infiltration with connective fibrotic extension. IHC revealed also increased hepatic myeloperoxidase (MPO) expression confirming neutrophils’ presence. In parallel, the histochemical study revealed a strong depletion of hepatocytic glycogen and lipid inclusions; these observations were also supported by the measurements of glycogen and total lipids in extracted tissue indicating a reduction in liver content. These results were accompanied by a decrease in body weight relative to the reduction of food intake, as well as hyperglycemia and some alterations in serum lipid parameters (triglycerides and cholesterol) suggesting a metabolic disturbance. Conclusion. We conclude that a phase difference between the endogenous activity rhythm of the species and the daily cycle of illumination has a strong impact on the liver morphology as well as on the metabolic activity of liver cells.

Abstract

Introduction. Biological rhythms, such as Light/Dark (LD) cycles, are an integral component of virtually all aspects of life. These rhythms are controlled in large part by circadian clocks, allowing the organism to adapt its internal rhythmic metabolism to changes in the external environment created by daily fluctuations in the LD cycle. Therefore, changes in the daily duration of the lighting could lead to adverse health consequences. The aim of the study was to investigate, in a nocturnal desert rodent, Gerbillus tarabuli, the effects of the LD cycle disruption on the structure of the hepatic tissue and the content of carbohydrate and lipid parameters as indicators of metabolic state. Material and methods. The present study was conducted on two gerbil groups: control group was exposed to a standard lighting cycle (LD: 12:12), and the shifted group was subjected to a chronic disrupted LD cycle, alternating a standard cycle (LD: 12:12) with a modified cycle (LD: 20:4), i.e., the light phase of 24-h cycle was prolonged by 8 h on every second day during a period of 12 weeks. We used: (i) routine histology and histochemical staining for tissue analysis; (ii) immunohistochemistry (IHC) for MPO detection; (iii) biochemical methods for hepatic glycogen and lipids extraction and quantification. Blood metabolic parameters were assessed by enzymatic methods. Results. Our structural results indicate in the shifted group an alteration of tissue architecture, showing widely scattered inflammatory foci with many dilated sinusoids and prominent leukocyte infiltration with connective fibrotic extension. IHC revealed also increased hepatic myeloperoxidase (MPO) expression confirming neutrophils’ presence. In parallel, the histochemical study revealed a strong depletion of hepatocytic glycogen and lipid inclusions; these observations were also supported by the measurements of glycogen and total lipids in extracted tissue indicating a reduction in liver content. These results were accompanied by a decrease in body weight relative to the reduction of food intake, as well as hyperglycemia and some alterations in serum lipid parameters (triglycerides and cholesterol) suggesting a metabolic disturbance. Conclusion. We conclude that a phase difference between the endogenous activity rhythm of the species and the daily cycle of illumination has a strong impact on the liver morphology as well as on the metabolic activity of liver cells.

Get Citation

Keywords

Gerbillus tarabuli; liver, photic desynchronization; liver structure; metabolism; myeloperoxidase

About this article
Title

The Light/Dark cycle disruption affects hepatic function both in metabolic parameters and tissue structure in a nocturnal desert rodent: Gerbillus tarabuli

Journal

Folia Histochemica et Cytobiologica

Issue

Vol 58, No 3 (2020)

Article type

Original paper

Pages

182-197

Published online

2020-09-22

DOI

10.5603/FHC.a2020.0021

Pubmed

32960973

Bibliographic record

Folia Histochem Cytobiol 2020;58(3):182-197.

Keywords

Gerbillus tarabuli
liver
photic desynchronization
liver structure
metabolism
myeloperoxidase

Authors

Amina Derbouz Rouibate
Nadir Benhafri
Saliha Ouali-Hassenaoui
Aicha Dekar-Madoui

References (90)
  1. Rosa RR, Bonnet MH, Bootzin RR, et al. Intervention factors for promoting adjustment to nightwork and shiftwork. Occup Med. 1990; 5(2):391–415. .
  2. Esseveldt Lv, Lehman M, Boer G. The suprachiasmatic nucleus and the circadian time-keeping system revisited. Brain Res Rev. 2000; 33(1): 34–77.
  3. Chou T, Scammell T, Gooley J, et al. Critical Role of Dorsomedial Hypothalamic Nucleus in a Wide Range of Behavioral Circadian Rhythms. J Neurosci. 2003; 23(33): 10691–10702.
  4. Challet E. Horloges circadiennes, troubles métaboliques et chronobésité. Obésité. 2009; 4(1): 73–85.
  5. Ralph MR, Foster RG, Davis FC, et al. Transplanted suprachiasmatic nucleus determines circadian period. Science. 1990; 247(4945): 975–978.
  6. Schibler U, Ripperger J, Brown SA. Peripheral circadian oscillators in mammals: time and food. J Biol Rhythms. 2003; 18(3): 250–260.
  7. Balsalobre A, Damiola F, Schibler U. A Serum Shock Induces Circadian Gene Expression in Mammalian Tissue Culture Cells. Cell. 1998; 93(6): 929–937.
  8. Kumar Jha P, Challet E, Kalsbeek A. Circadian rhythms in glucose and lipid metabolism in nocturnal and diurnal mammals. Mol Cell Endocrinol. 2015; 418 Pt 1: 74–88.
  9. Bray MS, Ratcliffe WF, Grenett MH, et al. Quantitative analysis of light-phase restricted feeding reveals metabolic dyssynchrony in mice. Int J Obes (Lond). 2013; 37(6): 843–852.
  10. Puttonen S, Härmä M, Hublin C. Shift work and cardiovascular disease - pathways from circadian stress to morbidity. Scand J Work Environ Health. 2010; 36(2): 96–108.
  11. Fritschi L, Glass DC, Heyworth JS, et al. Hypotheses for mechanisms linking shiftwork and cancer. Med Hypotheses. 2011; 77(3): 430–436.
  12. Stevens RG. Light-at-night, circadian disruption and breast cancer: assessment of existing evidence. Int J Epidemiol. 2009; 38(4): 963–970.
  13. Kohyama J. A newly proposed disease condition produced by light exposure during night: asynchronization. Brain Dev. 2009; 31(4): 255–273.
  14. Scheer FA, Hilton MF, Mantzoros CS, et al. Adverse metabolic and cardiovascular consequences of circadian misalignment. Proc Natl Acad Sci U S A. 2009; 106(11): 4453–4458.
  15. Bedrosian TA, Nelson RJ. Influence of the modern light environment on mood. Mol Psychiatry. 2013; 18(7): 751–757.
  16. Karlsson B, Knutsson A, Lindahl B. Is there an association between shift work and having a metabolic syndrome? Results from a population based study of 27,485 people. Occup Environ Med. 2001; 58(11): 747–752.
  17. Knutsson A. Health disorders of shift workers. Occup Med (Lond). 2003; 53(2): 103–108.
  18. Hassid WZ, Abraham S. [7] Chemical procedures for analysis of polysaccharides. Methods Enzymol. 1957: 34–50.
  19. Trinder P. Determination of Glucose in Blood Using Glucose Oxidase with an Alternative Oxygen Acceptor. Ann Clin Biochem. 1969; 6(1): 24–27.
  20. Folch J, Lees M SGHS. A simple method for the isolation on purification of total lipids from animal tissues. J Biol Chem. 1957; 226(1):497–235. .
  21. Martoja R, Martoja-Pierson M. Initiation aux techniques de l’histologie animale. Elsevier Masson. ; 1967.
  22. Albrecht U, Eichele G. The mammalian circadian clock. Curr Opin Genet Dev. 2003; 13(3): 271–277.
  23. Reppert SM, Weaver DR. Molecular analysis of mammalian circadian rhythms. Annu Rev Physiol. 2001; 63: 647–676.
  24. Mercer JG, Moar KM, Logie TJ, et al. Seasonally inappropriate body weight induced by food restriction: effect on hypothalamic gene expression in male Siberian hamsters. Endocrinology. 2001; 142(10): 4173–4181.
  25. Huang Z, Liu Q, Peng Yu, et al. Circadian Rhythm Dysfunction Accelerates Disease Progression in a Mouse Model With Amyotrophic Lateral Sclerosis. Front Neurol. 2018; 9: 218.
  26. McDonald RB, Hoban-Higgins TM, Ruhe RC, et al. Alterations in endogenous circadian rhythm of core temperature in senescent Fischer 344 rats. Am J Physiol. 1999; 276(3 Pt 2): R824–R830.
  27. Sen S, Raingard H, Dumont S, et al. Ultradian feeding in mice not only affects the peripheral clock in the liver, but also the master clock in the brain. Chronobiol Int. 2017; 34(1): 17–36.
  28. Karatsoreos IN, Bhagat S, Bloss EB, et al. Disruption of circadian clocks has ramifications for metabolism, brain, and behavior. Proc Natl Acad Sci U S A. 2011; 108(4): 1657–1662.
  29. de Goede P, Sen S, Su Y, et al. An Ultradian Feeding Schedule in Rats Affects Metabolic Gene Expression in Liver, Brown Adipose Tissue and Skeletal Muscle with Only Mild Effects on Circadian Clocks. Int J Mol Sci. 2018; 19(10).
  30. Fonken LK, Workman JL, Walton JC, et al. Light at night increases body mass by shifting the time of food intake. Proc Natl Acad Sci U S A. 2010; 107(43): 18664–18669.
  31. Coomans CP, van den Berg SAA, Houben T, et al. Detrimental effects of constant light exposure and high-fat diet on circadian energy metabolism and insulin sensitivity. FASEB J. 2013; 27(4): 1721–1732.
  32. Shi Sq, Ansari TS, McGuinness OP, et al. Circadian disruption leads to insulin resistance and obesity. Curr Biol. 2013; 23(5): 372–381.
  33. Dauchy RT, Dauchy EM, Tirrell RP, et al. Dark-phase light contamination disrupts circadian rhythms in plasma measures of endocrine physiology and metabolism in rats. Comp Med. 2010; 60(5):348–356. .
  34. Kettner NM, Voicu H, Finegold MJ, et al. Circadian Homeostasis of Liver Metabolism Suppresses Hepatocarcinogenesis. Cancer Cell. 2016; 30(6): 909–924.
  35. Challet E. Circadian clocks, food intake, and metabolism. Prog Mol Biol Transl Sci. 2013; 119: 105–135.
  36. Stokkan KA, Yamazaki S, Tei H, et al. Entrainment of the circadian clock in the liver by feeding. Science. 2001; 291(5503): 490–493.
  37. Tarquini R, Mazzoccoli G. Clock Genes, Metabolism, and Cardiovascular Risk. Heart Fail Clin. 2017; 13(4): 645–655.
  38. Manoogian ENC, Panda S. Circadian rhythms, time-restricted feeding, and healthy aging. Ageing Res Rev. 2017; 39: 59–67.
  39. Damiola F, Le Minh N, Preitner N, et al. Restricted feeding uncouples circadian oscillators in peripheral tissues from the central pacemaker in the suprachiasmatic nucleus. Genes Dev. 2000; 14(23): 2950–2961.
  40. Challet E, Malan A, Turek FW, et al. Daily variations of blood glucose, acid-base state and PCO2 in rats: effect of light exposure. Neurosci Lett. 2004; 355(1-2): 131–135.
  41. Gale JE, Cox HI, Qian J, et al. Disruption of circadian rhythms accelerates development of diabetes through pancreatic beta-cell loss and dysfunction. J Biol Rhythms. 2011; 26(5): 423–433.
  42. Nagai K, Nagai N, Sugahara K, et al. Circadian rhythms and energy metabolism with special reference to the suprachiasmatic nucleus. Neurosci Biobehav Rev. 1994; 18(4): 579–584.
  43. Turek FW, Joshu C, Kohsaka A, et al. Obesity and metabolic syndrome in circadian Clock mutant mice. Science. 2005; 308(5724): 1043–1045.
  44. Yamazaki S, Numano R, Abe M, et al. Resetting central and peripheral circadian oscillators in transgenic rats. Science. 2000; 288(5466): 682–685.
  45. Szántóová K, Zeman M, Veselá A, et al. Effect of phase delay lighting rotation schedule on daily expression of per2, bmal1, rev-erbα, pparα, and pdk4 genes in the heart and liver of Wistar rats. Mol Cell Biochem. 2011; 348(1-2): 53–60.
  46. Doi R, Oishi K, Ishida N. CLOCK regulates circadian rhythms of hepatic glycogen synthesis through transcriptional activation of Gys2. J Biol Chem. 2010; 285(29): 22114–22121.
  47. Schmutz I, Ripperger JA, Baeriswyl-Aebischer S, et al. The mammalian clock component PERIOD2 coordinates circadian output by interaction with nuclear receptors. Genes Dev. 2010; 24(4): 345–357.
  48. Zhao Y, Zhang Y, Zhou M, et al. Loss of mPer2 increases plasma insulin levels by enhanced glucose-stimulated insulin secretion and impaired insulin clearance in mice. FEBS Lett. 2012; 586(9): 1306–1311.
  49. Zani F, Breasson L, Becattini B, et al. PER2 promotes glucose storage to liver glycogen during feeding and acute fasting by inducing Gys2 PTG and G L expression. Mol Metab. 2013; 2(3): 292–305.
  50. Voet D, Voet JG, Pratt CW. Principles of Biochemistry. John Wiley & Sons. ; 2008.
  51. Pearson MJ, Unger RH, Holland WL. Clinical Trials, Triumphs, and Tribulations of Glucagon Receptor Antagonists. Diabetes Care. 2016; 39(7): 1075–1077.
  52. Panda S, Antoch M, Miller B, et al. Coordinated Transcription of Key Pathways in the Mouse by the Circadian Clock. Cell. 2002; 109(3): 307–320.
  53. Storch K-F, Lipan O, Leykin I, et al. Extensive and divergent circadian gene expression in liver and heart. Nature. 2002; 417(6884):78–83. .
  54. Lamia KA, Storch KF, Weitz CJ. Physiological significance of a peripheral tissue circadian clock. Proc Natl Acad Sci U S A. 2008; 105(39): 15172–15177.
  55. Reinke H, Asher G. Circadian Clock Control of Liver Metabolic Functions. Gastroenterology. 2016; 150(3): 574–580.
  56. Romon M, Nuttens MC, Fievet C, et al. Increased triglyceride levels in shift workers. Am J Med. 1992; 93(3): 259–262.
  57. Itani O, Kaneita Y, Tokiya M, et al. Short sleep duration, shift work, and actual days taken off work are predictive life-style risk factors for new-onset metabolic syndrome: a seven-year cohort study of 40,000 male workers. Sleep Med. 2017; 39: 87–94.
  58. Lu YC, Wang CP, Yu TH, et al. Shift work is associated with metabolic syndrome in male steel workers-the role of resistin and WBC count-related metabolic derangements. Diabetol Metab Syndr. 2017; 9: 83.
  59. Pan X, Hussain MM. Clock is important for food and circadian regulation of macronutrient absorption in mice. J Lipid Res. 2009; 50(9): 1800–1813.
  60. Pan X, Hussain MM. Diurnal regulation of microsomal triglyceride transfer protein and plasma lipid levels. J Biol Chem. 2007; 282(34): 24707–24719.
  61. Rudic RD, McNamara P, Curtis AM, et al. BMAL1 and CLOCK, two essential components of the circadian clock, are involved in glucose homeostasis. PLoS Biol. 2004; 2(11): e377.
  62. Grimaldi B, Bellet MM, Katada S, et al. PER2 controls lipid metabolism by direct regulation of PPARγ. Cell Metab. 2010; 12(5): 509–520.
  63. Su Y, Foppen E, Mansur Machado FS, et al. The role of the daily feeding rhythm in the regulation of the day/night rhythm in triglyceride secretion in rats. Chronobiol Int. 2018; 35(7): 885–895.
  64. Pan X, Munshi MK, Iqbal J, et al. Circadian regulation of intestinal lipid absorption by apolipoprotein AIV involves forkhead transcription factors A2 and O1 and microsomal triglyceride transfer protein. J Biol Chem. 2013; 288(28): 20464–20476.
  65. Shamsi NA, Salkeld MD, Rattanatray L, et al. Metabolic consequences of timed feeding in mice. Physiol Behav. 2014; 128: 188–201.
  66. Yasumoto Y, Hashimoto C, Nakao R, et al. Short-term feeding at the wrong time is sufficient to desynchronize peripheral clocks and induce obesity with hyperphagia, physical inactivity and metabolic disorders in mice. Metabolism. 2016; 65(5): 714–727.
  67. Bailey SM, Udoh US, Young ME. Circadian regulation of metabolism. J Endocrinol. 2014; 222(2): R75–R96.
  68. Gimble JM, Floyd ZE. Fat circadian biology. J Appl Physiol (1985). 2009; 107(5): 1629–1637.
  69. Sassolas A, Cartier R. Hypocholesterolemias: causes and diagnosis. Ann Biol Clin. 1999; 57(5):555–60. .
  70. Adamovich Y, Aviram R, Asher G. The emerging roles of lipids in circadian control. Biochim Biophys Acta. 2015; 1851(8): 1017–1025.
  71. Mathurin P, Poynard T. Pharmacological treatment for alcoholic hepatitis and cirrhosis. Ethanol and the Liver. 2013: 592–613.
  72. SAWADOGO A, DIB N, CALES P. Physiopathologie de la cirrhose et de ses complications. Réanimation. 2007; 16(7-8): 557–562.
  73. Suffredini A, Fantuzzi G, Badolato R, et al. New insights into the biology of the acute phase response. J Clin Immunol. 1999; 19(4): 203–214.
  74. Gregory SH, Wing EJ. Neutrophil-Kupffer cell interaction: a critical component of host defenses to systemic bacterial infections. J Leukoc Biol. 2002; 72(2):239–248. .
  75. Wick M, Leithauser F, Reimann J. The Hepatic Immune System. Crit Rev Immunol. 2002; 22(1): 57.
  76. Jawhara S, Thuru X, Standaert-Vitse A, et al. Colonization of mice by Candida albicans is promoted by chemically induced colitis and augments inflammatory responses through galectin-3. J Infect Dis. 2008; 197(7): 972–980.
  77. Kim HW, Uh DK, Yoon SY, et al. Low-frequency electroacupuncture suppresses carrageenan-induced paw inflammation in mice via sympathetic post-ganglionic neurons, while high-frequency EA suppression is mediated by the sympathoadrenal medullary axis. Brain Res Bull. 2008; 75(5): 698–705.
  78. Faith M, Sukumaran A, Pulimood AB, et al. How reliable an indicator of inflammation is myeloperoxidase activity? Clin Chim Acta. 2008; 396(1-2): 23–25.
  79. McConnico RS, Weinstock D, Poston ME, et al. Myeloperoxidase activity of the large intestine in an equine model of acute colitis. Am J Vet Res. 1999; 60(7):807–813. .
  80. Zhang C, Patel R, Eiserich JP, et al. Endothelial dysfunction is induced by proinflammatory oxidant hypochlorous acid. Am J Physiol Heart Circ Physiol. 2001; 281(4): H1469–H1475.
  81. Hoy A, Leininger-Muller B, Kutter D, et al. Growing significance of myeloperoxidase in non-infectious diseases. Clin Chem Lab Med. 2002; 40(1): 2–8.
  82. Heinecke J. Mechanisms of oxidative damage by myeloperoxidase in atherosclerosis and other inflammatory disorders. J Lab Clin Med. 1999; 133(4): 321–325.
  83. Nahon P, Sutton A, Rufat P, et al. Myeloperoxidase and superoxide dismutase 2 polymorphisms comodulate the risk of hepatocellular carcinoma and death in alcoholic cirrhosis. Hepatology. 2009; 50(5): 1484–1493.
  84. Winterbourn CC, Brennan SO. Characterization of the oxidation products of the reaction between reduced glutathione and hypochlorous acid. Biochem J. 1997; 326 ( Pt 1): 87–92.
  85. Jarnagin WR, Rockey DC, Koteliansky VE, et al. Expression of variant fibronectins in wound healing: cellular source and biological activity of the EIIIA segment in rat hepatic fibrogenesis. J Cell Biol. 1994; 127(6 Pt 2): 2037–2048.
  86. Gressner AM, Bachem MG. Molecular mechanisms of liver fibrogenesis--a homage to the role of activated fat-storing cells. Digestion. 1995; 56(5): 335–346.
  87. Bekheet IW, Madkour ME, Ghaffar N, et al. The Role of Myeloperoxidase in Hepatitis C Virus Infection and Associated Liver Cirrhosis. Open Trop Med J. 2009; 2(1): 1–7.
  88. Abdel-Hamid M, Nada O, Ellakwa DS, et al. Role of Myeloperoxidase in hepatitis C virus related hepatocellular carcinoma. Meta Gene. 2018; 18: 1–8.
  89. Friedman SL. Hepatic stellate cells: protean, multifunctional, and enigmatic cells of the liver. Physiol Rev. 2008; 88(1): 125–172.
  90. DeLeve LD, Jaeschke H, Kalra VK, et al. 15th International Symposium on Cells of the Hepatic Sinusoid, 2010. Liver Int. 2011; 31(6): 762–772.

Regulations

Important: This website uses cookies. More >>

The cookies allow us to identify your computer and find out details about your last visit. They remembering whether you've visited the site before, so that you remain logged in - or to help us work out how many new website visitors we get each month. Most internet browsers accept cookies automatically, but you can change the settings of your browser to erase cookies or prevent automatic acceptance if you prefer.

By "Via Medica sp. z o.o." sp.k., ul. Świętokrzyska 73, 80–180 Gdańsk

tel.:+48 58 320 94 94, faks:+48 58 320 94 60, e-mail:  viamedica@viamedica.pl