Abstract
The major function of the circadian system is the internal cycling of physiologic and metabolic events. In the last years, there has been an exponential increase in our understanding of the role of clock-related genes in Metabolic-syndrome (MetS)-related phenotypes. Nevertheless, our understanding about how the components of the circadian system interact each other to modulate the metabolism and cardiovascular system remains a major challenge.
Systems biology introduces a new concept for revealing the pathogenesis of human disorders and suggests the presence of common physiologic processes and molecular networks influencing the risk of a disease. In this review, we use systems biology approaches to integrate genomic, molecular, and physiological data to decipher putative circadian rhythmic pathways suspected to play a role in the etiology of the metabolic syndrome (MetS)-associated phenotypes with a main focus in obesity and as other authors are discussing diverse related topics, we discuss the findings of our own group.
This is a preview of subscription content, log in via an institution to check access.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
Similar content being viewed by others
Abbreviations
- MetS:
-
Metabolic syndrome
- IR:
-
Insulin resistance
- T2D:
-
Type-2 diabetes
- GWAS:
-
Genome-wide association scan
- CLOCK:
-
Circadian locomotor output cycles kaput protein
- 5-HT:
-
Serotonin
- 5-HTT:
-
Serotonin transporter
- 5HIAA:
-
5-Hydroxyindolacetic acid
- PPARG1A:
-
Peroxisome proliferator-activated receptor gamma cofactor 1 alpha gene
References
Reaven GM (1998) Insulin resistance may or may not play a role in blood pressure regulation. J Intern Med 244(4):359–360
Sookoian S, Gianotti TF, Schuman M, Pirola CJ (2009) Gene prioritization based on biological plausibility over genome wide association studies renders new loci associated with type 2 diabetes. Genet Med 11(5):338–343
Sookoian S, Pirola CJ (2011) Metabolic syndrome: from the genetics to the pathophysiology. Curr Hypertens Rep 13(2):149–157
Turek FW, Joshu C, Kohsaka A, Lin E, Ivanova G, McDearmon E et al (2005) Obesity and metabolic syndrome in circadian Clock mutant mice. Science 308(5724):1043–1045
Eckel-Mahan KL, Patel VR, Mohney RP, Vignola KS, Baldi P, Sassone-Corsi P (2012) Coordination of the transcriptome and metabolome by the circadian clock. Proc Natl Acad Sci U S A 109(14):5541–5546
Sookoian S, Gemma C, Gianotti TF, Burgueno A, Castano G, Pirola CJ (2008) Genetic variants of Clock transcription factor are associated with individual susceptibility to obesity. Am J Clin Nutr 87(6):1606–1615
Scott EM, Carter AM, Grant PJ (2008) Association between polymorphisms in the Clock gene, obesity and the metabolic syndrome in man. Int J Obes (Lond) 32(4):658–662
Garaulet M, Corbalan MD, Madrid JA, Morales E, Baraza JC, Lee YC et al (2010) CLOCK gene is implicated in weight reduction in obese patients participating in a dietary programme based on the Mediterranean diet. Int J Obes (Lond) 34(3):516–523
Garaulet M, Lee YC, Shen J, Parnell LD, Arnett DK, Tsai MY et al (2009) CLOCK genetic variation and metabolic syndrome risk: modulation by monounsaturated fatty acids. Am J Clin Nutr 90(6):1466–1475
Sookoian S, Castano G, Gemma C, Gianotti TF, Pirola CJ (2007) Common genetic variations in CLOCK transcription factor are associated with nonalcoholic fatty liver disease. World J Gastroenterol 13(31):4242–4248
Maury E, Ramsey KM, Bass J (2010) Circadian rhythms and metabolic syndrome: from experimental genetics to human disease. Circ Res 106(3):447–462
Stubblefield JJ, Terrien J, Green CB (2012) Nocturnin: at the crossroads of clocks and metabolism. Trends Endocrinol Metab 23(7):326–333 [Epub ahead of print]
Barbosa-Silva A, Fontaine JF, Donnard ER, Stussi F, Ortega JM, Andrade-Navarro MA (2011) PESCADOR, a web-based tool to assist text-mining of biointeractions extracted from PubMed queries. BMC Bioinformatics 12:435–444
Vidal M (2005) Interactome modeling. FEBS Lett 579(8):1834–1838
Chen J, Bardes EE, Aronow BJ, Jegga AG (2009) ToppGene Suite for gene list enrichment analysis and candidate gene prioritization. Nucleic Acids Res 37(Web Server issue): W305–W311
Sookoian S, Gemma C, Pirola CJ (2010) Influence of hepatocyte nuclear factor 4alpha (HNF4alpha) gene variants on the risk of type 2 diabetes: a meta-analysis in 49,577 individuals. Mol Genet Metab 99(1):80–89
Sookoian S, Gianotti TF, Gemma C, Burgueno AL, Pirola CJ (2010) Role of genetic variation in insulin-like growth factor 1 receptor on insulin resistance and arterial hypertension. J Hypertens 28(6):1194–1202
Sookoian S, Gemma C, Garcia SI, Gianotti TF, Dieuzeide G, Roussos A et al (2007) Short allele of serotonin transporter gene promoter is a risk factor for obesity in adolescents SOOKOIAN2007A. Obesity (Silver Spring) 15(2):271–276
Sookoian S, Gianotti TF, Gemma C, Burgueno A, Pirola CJ (2008) Contribution of the functional 5-HTTLPR variant of the slc6a4 gene to obesity risk in male adults SOOKOIAN2008. Obesity (Silver Spring) 16(2):488–491
Burgueno A, Gemma C, Gianotti TF, Sookoian S, Pirola CJ (2010) Increased levels of resistin in rotating shift workers: a potential mediator of cardiovascular risk associated with circadian misalignment. Atherosclerosis 210(2):625–629
Sookoian S, Gemma C, Fernandez GT, Burgueno A, Alvarez A, Gonzalez CD et al (2007) Effects of rotating shift work on biomarkers of metabolic syndrome and inflammation SOOKOIAN2007. J Intern Med 261(3):285–292
Sookoian S, Pirola CJ (2009) Shift work and subclinical atherosclerosis: recommendations for fatty liver disease detection. Atherosclerosis 207(2):346–347
Warde-Farley D, Donaldson SL, Comes O, Zuberi K, Badrawi R, Chao P et al (2010) The GeneMANIA prediction server: biological network integration for gene prioritization and predicting gene function. Nucleic Acids Res 38(Web Server issue):W214–W220
Esterbauer H, Oberkofler H, Krempler F, Patsch W (1999) Human peroxisome proliferator activated receptor gamma coactivator 1 (PPARGC1) gene: cDNA sequence, genomic organization, chromosomal localization, and tissue expression. Genomics 62(1):98–102
Finck BN, Kelly DP (2006) PGC-1 coactivators: inducible regulators of energy metabolism in health and disease. J Clin Invest 116(3):615–622
Sookoian S, Garcia SI, Porto PI, Dieuzeide G, Gonzalez CD, Pirola CJ (2005) Peroxisome proliferator-activated receptor gamma and its coactivator-1 alpha may be associated with features of the metabolic syndrome in adolescents. J Mol Endocrinol 35(2):373–380
Sookoian S, Rosselli MS, Gemma C, Burgueno AL, Fernandez GT, Castano GO et al (2010) Epigenetic regulation of insulin resistance in nonalcoholic fatty liver disease: impact of liver methylation of the peroxisome proliferator-activated receptor gamma coactivator 1alpha promoter. Hepatology 52(6):1992–2000
Li S, Zhao JH, Luan J, Luben RN, Rodwell SA, Khaw KT et al (2010) Cumulative effects and predictive value of common obesity-susceptibility variants identified by genome-wide association studies. Am J Clin Nutr 91(1):184–190
Tomaszewski M, Charchar FJ, Lacka B, Pesonen U, Wang WY, Zukowska-Szczechowska E et al (2004) Epistatic interaction between beta2-adrenergic receptor and neuropeptide Y genes influences LDL-cholesterol in hypertension. Hypertension 44(5):689–694
Baessler A, Fischer M, Mayer B, Koehler M, Wiedmann S, Stark K et al (2007) Epistatic interaction between haplotypes of the ghrelin ligand and receptor genes influence susceptibility to myocardial infarction and coronary artery disease. Hum Mol Genet 16(8):887–899
Isaacs A, Aulchenko YS, Hofman A, Sijbrands EJ, Sayed-Tabatabaei FA, Klungel OH et al (2007) Epistatic effect of cholesteryl ester transfer protein and hepatic lipase on serum high-density lipoprotein cholesterol levels. J Clin Endocrinol Metab 92(7):2680–2687
Brisson D, St-Pierre J, Santure M, Hudson TJ, Despres JP, Vohl MC et al (2007) Genetic epistasis in the VLDL catabolic pathway is associated with deleterious variations on triglyceridemia in obese subjects. Int J Obes (Lond) 31(8):1325–1333
Sookoian S, Gianotti TF, Burgueno A, Pirola CJ (2010) Gene–gene interaction between serotonin transporter (SLC6A4) and clock modulates the risk of metabolic syndrome in rotating shiftworkers. Chronobiol Int 27(6):1202–1218
Ling C, Del GS, Lupi R, Ronn T, Granhall C, Luthman H et al (2008) Epigenetic regulation of PPARGC1A in human type 2 diabetic islets and effect on insulin secretion. Diabetologia 51(4):615–622
Gemma C, Sookoian S, Alvarinas J, Garcia SI, Quintana L, Kanevsky D et al (2009) Maternal pregestational BMI is associated with methylation of the PPARGC1A promoter in newborns. Obesity (Silver Spring) 17(5):1032–1039
Gemma C, Sookoian S, Dieuzeide G, Garcia SI, Gianotti TF, Gonzalez CD et al (2010) Methylation of TFAM gene promoter in peripheral white blood cells is associated with insulin resistance in adolescents. Mol Genet Metab 100(1):83–87
Gemma C, Sookoian S, Alvarinas J, Garcia SI, Quintana L, Kanevsky D et al (2006) Mitochondrial DNA Depletion in Small- and Large-for-Gestational-Age Newborns. Obesity (Silver Spring) 14(12):2193–2199
Gianotti TF, Sookoian S, Dieuzeide G, Garcia SI, Gemma C, Gonzalez CD et al (2008) A Decreased Mitochondrial DNA Content Is Related to Insulin Resistance in Adolescents. Obesity 16(7):1591–1595
Smith L, Macdonald I, Folkard S, Tucker P (1998) Industrial shift systems. Appl Ergon 29(4):273–280
List of Bioinformatic Resources
PESCADOR: available at: http://cbdm.mdc-berlin.de/tools/pescador/
ToppGene Suite: available at: http://toppgene.cchmc.org
GeneMANIA: available at: http://www.genemania.org
KEGG: Kyoto Encyclopedia of Genes and Genomes: available at: http://www.genome.jp/kegg
Acknowledgments
This study was partially supported by grants PICT 2008-1521 and 2010-0441 (Agencia Nacional de Promoción Científica y Tecnológica), and UBACYT CM04 (Universidad de Buenos Aires). S.S. and C.J.P. belong to CONICET.
Author information
Authors and Affiliations
Corresponding authors
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2013 Springer Science+Business Media New York
About this chapter
Cite this chapter
Sookoian, S., Pirola, C.J. (2013). Chronobiology and Metabolic Syndrome: From Genes to Systems Biology. In: Garaulet, M., Ordovás, J. (eds) Chronobiology and Obesity. Springer, New York, NY. https://doi.org/10.1007/978-1-4614-5082-5_9
Download citation
DOI: https://doi.org/10.1007/978-1-4614-5082-5_9
Published:
Publisher Name: Springer, New York, NY
Print ISBN: 978-1-4614-5081-8
Online ISBN: 978-1-4614-5082-5
eBook Packages: Biomedical and Life SciencesBiomedical and Life Sciences (R0)