Abstract
In many biomedical research areas, animals have been used as a model to increase the understanding of molecular mechanisms involved in human diseases. One of those areas is human obesity, where porcine models are increasingly used. The pig shows genetic and physiological features that are very similar to humans and have shown to be an excellent model for human obesity. Using pig populations, many genetic studies have been performed to unravel the genetic architecture of human obesity. Most of them are pinpointing toward single genes, but more and more studies focus on a systems genetics approach, a branch of systems biology. In this chapter, we will describe the state of the art of genetic studies on human obesity, using pig populations. We will describe the features of using the pig as a model for human obesity and briefly discuss the genetics of obesity, and we will focus on systems genetic research performed using pigs with their contribution to human obesity research.
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Bendixen E, Danielsen M, Larsen K, Bendixen C (2010) Advances in porcine genomics and proteomics—a toolbox for developing the pig as a model organism for molecular biomedical research. Brief Funct Genomics 9(3):208–219. doi:10.1093/bfgp/elq004
Bidanel J, Milan D, Iannuccelli N et al (2001) Detection of quantitative trait loci for growth and fatness in pigs. Genet Sel Evol 33:289–309. doi:10.1186/1297-9686-33-3-289
Bollen PJ, Madsen LW, Meyer O, Ritskes-Hoitinga J (2005) Growth differences of male and female Gottingen minipigs during ad libitum feeding: a pilot study. Lab Anim 39(1):80–93. doi:10.1258/0023677052886565
Bougnères P (2002) Genetics of obesity and type 2 diabetes. Diabetes 51(suppl 3):S295–S303. doi:10.2337/diabetes.51.2007.S295
Chen C, Ai H, Ren J et al (2011) A global view of porcine transcriptome in three tissues from a full-sib pair with extreme phenotypes in growth and fat deposition by paired-end RNA sequencing. BMC Genomics 12:448. doi:10.1186/1471-2164-12-448
Cirera S, Jensen MS, Elbrønd VS et al (2014) Expression studies of six human obesity-related genes in seven tissues from divergent pig breeds. Anim Genet 45(1):59–66. doi:10.1111/age.12082
Curtus H, Barnes NS (1994) Invitation to biology, vol 529, 5th edn. Worth, New York
Davis MA, Henry R, Leslie RB (1974) Comparative studies on porcine and human high density lipoproteins. Comp Biochem Physiol B 47(4):831–849
Davoli R, Braglia S, Valastro V et al (2012) Analysis of MC4R polymorphism in Italian Large White and Italian Duroc pigs: association with carcass traits. Meat Sci 90(4):887–892. doi:10.1016/j.meatsci.2011.11.025
de Koning D, Janss L, Rattink A et al (1999) Detection of quantitative trait loci for backfat thickness and intramuscular fat content in pigs (Sus scrofa). Genetics 152:1679–1690
Diez J, Iglesias P (2003) The role of the novel adipocyte-derived hormone adiponectin in human disease. Eur J Endocrinol 148(3):293–300. doi:10.1530/eje.0.1480293
Do DN, Strathe AB, Ostersen T, Jensen J, Mark T, Kadarmideen HN (2013) Genome-wide association study reveals genetic architecture of eating behavior in pigs and its implications for humans obesity by comparative mapping. PLoS One 8(8), e71509. doi:10.1371/journal.pone.0071509
Dyson MC, Alloosh M, Vuchetich JP, Mokelke EA, Sturek M (2006) Components of metabolic syndrome and coronary artery disease in female Ossabaw swine fed excess atherogenic diet. Comp Med 56(1):35–45
Elgazar-Carmon V, Rudich A, Hadad N, Levy R (2008) Neutrophils transiently infiltrate intra-abdominal fat early in the course of high-fat feeding. J Lipid Res 49(9):1894–1903. doi:10.1194/jlr.M800132-JLR200
Fan B, Du ZQ, Rothschild MF (2009) The fat mass and obesity-associated (FTO) gene is associated with intramuscular fat content and growth rate in the pig. Anim Biotechnol 20(2):58–70. doi:10.1080/10495390902800792
Fan B, Onteru SK, Du Z-Q, Garrick DJ, Stalder KJ, Rothschild MF (2011) Genome-wide association study identifies loci for body composition and structural soundness traits in pigs. PLoS One 6(2), e14726. doi:10.1371/journal.pone.0014726
Fantuzzi G (2005) Adipose tissue, adipokines, and inflammation. J Allergy Clin Immunol 115(5):911–919. doi:10.1016/j.jaci.2005.02.023
Ferrante AW (2013) The immune cells in adipose tissue. Diabetes Obes Metab 15(s3):34–38. doi:10.1111/dom.12154
Fontanesi L, Scotti E, Buttazzoni L, Davoli R, Russo V (2009) The porcine fat mass and obesity associated (FTO) gene is associated with fat deposition in Italian Duroc pigs. Anim Genet 40(1):90–93. doi:10.1111/j.1365-2052.2008.01777.x
Fontanesi L, Scotti E, Buttazzoni L et al (2010) Confirmed association between a single nucleotide polymorphism in the FTO gene and obesity-related traits in heavy pigs. Mol Biol Rep 37(1):461–466. doi:10.1007/s11033-009-9638-8
Friedman JM (2002) The function of leptin in nutrition, weight, and physiology. Nutr Rev 60(suppl 10):S1–S14. doi:10.1301/002966402320634878
Galgani J, Ravussin E (2010) Energy metabolism, fuel selection and body weight regulation. Int J Obes (Lond) 32(Suppl 7):S109–S119. doi:10.1038/ijo.2008.246
Gray H (1918) Anatomy of the human body. Lea & Febiger
Groenen MAM, Archibald AL, Uenishi H et al (2012) Analyses of pig genomes provide insight into porcine demography and evolution. Nature 491(7424):393–398. doi:10.1038/nature11622
Gurr MI, Kirtland J, Phillip M, Robinson MP (1977) The consequences of early overnutrition for fat cell size and number: the pig as an experimental model for human obesity. Int J Obes (Lond) 1(2):151–170
Halsted CH (1999) Obesity: effects on the liver and gastrointestinal system. Curr Opin Clin Nutr Metab Care 2(5):425–429
Hau J (2008) Animal models for human diseases. In: Conn PM (ed) Sourcebook of models for biomedical research. Humana Press, Totowa, pp 3–8. doi:10.1007/978-1-59745-285-4_1
He Q, Ren P, Kong X et al (2012) Comparison of serum metabolite compositions between obese and lean growing pigs using an NMR-based metabonomic approach. J Nutr Biochem 23(2):133–139. doi:10.1016/j.jnutbio.2010.11.007
Heber D (2010) An integrative view of obesity. Am J Clin Nutr 91(1):280S–283S. doi:10.3945/ajcn.2009.28473B
Houpt KA, Houpt TR, Pond WG (1979) The pig as a model for the study of obesity and of control of food intake: a review. Yale J Biol Med 52(3):307–329
Houston RD, Cameron ND, Rance KA (2004) A melanocortin-4 receptor (MC4R) polymorphism is associated with performance traits in divergently selected Large White pig populations. Anim Genet 35(5):386–390. doi:10.1111/j.1365-2052.2004.01182.x
Hwang H, Bowen BP, Lefort N et al (2010) Proteomics analysis of human skeletal muscle reveals novel abnormalities in obesity and type 2 diabetes. Diabetes 59(1):33–42. doi:10.2337/db09-0214
Jacobsen MJ, Mentzel CMJ, Olesen AS et al (2016) Altered methylation profile of lymphocytes is concordant with perturbation of lipids metabolism and inflammatory response in obesity. J Diabet Res 2016:11. doi:10.1155/2016/8539057
Johansen T, Hansen HS, Richelsen B, Malmlöf K (2001) The obese Gottingen minipig as a model of the metabolic syndrome: dietary effects on obesity, insulin sensitivity, and growth hormone profile. Comp Med 51(2):150–155
Kim J, Lee T, Kim T-H, Lee K-T, Kim H (2012) An integrated approach of comparative genomics and heritability analysis of pig and human on obesity trait: evidence for candidate genes on human chromosome 2. BMC Genomics 13:711. doi:10.1186/1471-2164-13-711
Kogelman LJA, Kadarmideen H (2014) Weighted Interaction SNP Hub (WISH) network method for building genetic networks for complex diseases and traits using whole genome genotype data. BMC Syst Biol 8(Suppl 2):S5. doi:10.1186/1752-0509-8-S2-S5
Kogelman LJA, Kadarmideen HN, Mark T et al (2013) An F2 pig resource population as a model for genetic studies of obesity and obesity-related diseases in humans: design and genetic parameters. Front Genet 4:29. doi:10.3389/fgene.2013.00029
Kogelman LJA, Cirera S, Zhernakova D, Fredholm M, Franke L, Kadarmideen H (2014a) Identification of co-expression gene networks, regulatory genes and pathways for obesity based on adipose tissue RNA Sequencing in a porcine model. BMC Med Genomics 7(1):57. doi:10.1186/1755-8794-7-57
Kogelman LJA, Pant SD, Fredholm M, Kadarmideen HN (2014b) Systems genetics of obesity in an F2 pig model by genome-wide association, genetic network and pathway analyses. Front Genet 5:214. doi:10.3389/fgene.2014.00214
Kogelman LAJ, Zhernakova DV, Westra H-J et al (2015) An integrative systems genetics approach reveals potential causal genes and pathways related to obesity. Genome Med 7(1):1–15. doi:10.1186/s13073-015-0229-0
Li K, Zhao H, Zhou J-C et al (2011) Differentially expressed genes in subcutaneous fat tissue in an obese pig model induced by a high-fat diet. J Anim Vet Adv 10(14):1804–1810. doi:10.3923/javaa.2011.1804.1810
Li A, Mo D, Zhao X et al (2013) Comparison of the longissimus muscle proteome between obese and lean pigs at 180 days. Mamm Genome 24(1–2):72–79. doi:10.1007/s00335-012-9440-0
Liu J, Divoux A, Sun J et al (2009) Deficiency and pharmacological stabilization of mast cells reduce diet-induced obesity and diabetes in mice. Nat Med 15(8):940–945. doi:10.1038/nm.1994
Locke AE, Kahali B, Berndt SI et al (2015) Genetic studies of body mass index yield new insights for obesity biology. Nature 518(7538):197–206. doi:10.1038/nature14177
Lubrano-Berthelier C, Cavazos M, Dubern B et al (2003) Molecular genetics of human obesity-associated MC4R mutations. Ann N Y Acad Sci 994:49–57
Lunney JK (2007) Advances in swine biomedical model genomics. Int J Biol Sci 3(3):179–184. doi:10.7150/ijbs.3.179
Madsen MB, Birck MM, Fredholm M, Cirera S (2009) Expression studies of the obesity candidate gene FTO in pig. Anim Biotechnol 21(1):51–63. doi:10.1080/10495390903381792
Marrades MP, Gonzalez-Muniesa P, Martinez JA, Moreno-Aliaga MJ (2010) A dysregulation in CES1, APOE and other lipid metabolism-related genes is associated to cardiovascular risk factors linked to obesity. Obes Facts 3(5):312–318. doi:10.1159/000321451
McAnulty PA, Dayan AD, Ganderup N-C, Hastings KL (2011) The minipig in biomedical research. RC Press, Boca Raton
Mentzel CMJ, Anthon C, Jacobsen MJ et al (2015) Gender and obesity specific MicroRNA expression in adipose tissue from lean and obese pigs. PLoS One 10(7), e0131650. doi:10.1371/journal.pone.0131650
Michael Swindle M, Smith A (2008) Swine in biomedical research. In: Conn PM (ed) Sourcebook of models for biomedical research. Humana Press, Totowa, pp 233–239. doi:10.1007/978-1-59745-285-4_26
Mitchell AD, Conway JM, Potts WJ (1996) Body composition analysis of pigs by dual-energy x-ray absorptiometry. J Anim Sci 74(11):2663–2671
Mitchell AD, Scholz AM, Conway JM (1998) Body composition analysis of small pigs by dual-energy x-ray absorptiometry. J Anim Sci 76(9):2392–2398
Molarius A, Seidell JC (1998) Selection of anthropometric indicators for classification of abdominal fatness--a critical review. Int J Obes Relat Metab Disord 22(8):719–727
Nowacka-Woszuk J, Szczerbal I, Fijak-Nowak H, Switonski M (2008) Chromosomal localization of 13 candidate genes for human obesity in the pig genome. J Appl Genet 49(4):373–377. doi:10.1007/bf03195636
O’Rahilly S, Farooqi I (2006) Genetics of obesity. Philos Trans Royal Soc B Biol Sci 361(1471):1095–1105. doi:10.1098/rstb.2006.1850
Okumura N, Matsumoto T, Hayashi T et al (2013) Genomic regions affecting backfat thickness and cannon bone circumference identified by genome-wide association study in a Duroc pig population. Anim Genet 44(4):454–457. doi:10.1111/age.12018
Pant SD, Karlskov-Mortensen P, Jacobsen MJ et al (2015) Comparative analyses of QTLs influencing obesity and metabolic phenotypes in pigs and humans. PLoS One 10(9), e0137356. doi:10.1371/journal.pone.0137356
Ponsuksili S, Murani E, Brand B, Schwerin M, Wimmers K (2011) Integrating expression profiling and whole-genome association for dissection of fat traits in a porcine model. J Lipid Res 52(4):668–678. doi:10.1194/jlr.M013342
Rauschert S, Uhl O, Koletzko B, Hellmuth C (2014) Metabolomic biomarkers for obesity in humans: a short review. Ann Nutr Metab 64(3–4):314–324. doi:10.1159/000365040
Razmaite V, Kerziene S, Jatkauskiene V (2009) Body and carcass measurements and organ weights of Lithuanian indigenous pigs and their wild boar hybrids. Anim Sci Papers Rep 27(4):331–342
Santini F, Maffei M, Pelosini C, Salvetti G, Scartabelli G, Pinchera A (2009) Melanocortin-4 receptor mutations in obesity. Adv Clin Chem 48:95–109
Scuteri A, Sanna S, Chen W-M et al (2007) Genome-wide association scan shows genetic variants in the FTO gene are associated with obesity-related traits. PLoS Genet 3(7), e115. doi:10.1371/journal.pgen.0030115
Shannon P, Markiel A, Ozier O et al (2003) Cytoscape: a software environment for integrated models of biomolecular interaction networks. Genome Res 13:2498–2504
Shoelson SE, Herrero L, Naaz A (2007) Obesity, inflammation, and insulin resistance. Gastroenterology 132(6):2169–2180. doi:10.1053/j.gastro.2007.03.059
Shungin D, Winkler TW, Croteau-Chonka DC et al (2015) New genetic loci link adipose and insulin biology to body fat distribution. Nature 518(7538):187–196. doi:10.1038/nature14132
Skinkyte-Juskiene R, Kogelman LJA, Kadarmideen HN (2015) Construction of transcription factor networks for obesity using RNAseq transcriptomics. In: Genome Informatics, Cold Spring Harbor
Speliotes EK, Willer CJ, Berndt SI et al (2010) Association analyses of 249,796 individuals reveal 18 new loci associated with body mass index. Nat Genet 42(11):937–948. doi:10.1038/ng.686
Spurlock ME, Gabler NK (2008) The development of porcine models of obesity and the metabolic syndrome. J Nutr 138(2):397–402
Steibel J, Bates R, Rosa G et al (2011) Genome-wide linkage analysis of global gene expression in loin muscle tissue identifies candidate genes in pigs. PLoS One 6, e16766. doi:10.1371/journal.pone.0016766
Suravajhala P, Kogelman LJA, Mazzoni G, Kadarmideen HN (2015) Potential role of lncRNA cyp2c91-protein interactions on diseases of the immune system. Front Genet 6:255. doi:10.3389/fgene.2015.00255
Suster D, Leury BJ, Ostrowska E et al (2003) Accuracy of dual energy X-ray absorptiometry (DXA), weight and P2 back fat to predict whole body and carcass composition in pigs within and across experiments. Livestock Prod Sci 84(3):231–242. doi:10.1016/S0301-6226(03)00077-0
te Pas MFW, Koopmans S-J, Kruijt L, Calus MPL, Smits MA (2013) Plasma proteome profiles associated with diet-induced metabolic syndrome and the early onset of metabolic syndrome in a pig model. PLoS One 8(9), e73087. doi:10.1371/journal.pone.0073087
Tilg H, Moschen AR (2006) Adipocytokines: mediators linking adipose tissue, inflammation and immunity. Nat Rev Immunol 6(10):772–783
Tolppanen A-M, Pulkkinen L, Kolehmainen M et al (2007) Tenomodulin is associated with obesity and diabetes risk: the Finnish diabetes prevention study. Obesity 15(5):1082–1088. doi:10.1038/oby.2007.613
van Dijk SJ, Tellam RL, Morrison JL, Muhlhausler BS, Molloy PL (2015) Recent developments on the role of epigenetics in obesity and metabolic disease. Clin Epigenet 7(1):1–13. doi:10.1186/s13148-015-0101-5
Vazquez G, Duval S, Jacobs DR, Silventoinen K (2007) Comparison of body mass index, waist circumference, and waist/hip ratio in predicting incident diabetes: a meta-analysis. Epidemiol Rev 29(1):115–128. doi:10.1093/epirev/mxm008
Walewski JL, Ge F, Gagner M et al (2010) Adipocyte accumulation of long-chain fatty acids in obesity is multifactorial, resulting from increased fatty acid uptake and decreased activity of genes involved in fat utilization. Obes Surg 20(1):93–107. doi:10.1007/s11695-009-0002-9
World Health Organization (2012) Obesity and overweight, Fact sheet No. 311 updated March 2013. http://www.who.int/mediacentre/factsheets/fs311/en/
Wren AM, Seal LJ, Cohen MA et al (2001) Ghrelin enhances appetite and increases food intake in humans. J Clin Endocrinol Metabol 86(12):5992. doi:10.1210/jcem.86.12.8111
Xu H, Barnes GT, Yang Q et al (2003) Chronic inflammation in fat plays a crucial role in the development of obesity-related insulin resistance. J Clin Invest 112(12):1821–1830. doi:10.1172/jci19451
Xu J, Li Y, Chen WD et al (2014) Hepatic carboxylesterase 1 is essential for both normal and farnesoid X receptor-controlled lipid homeostasis. Hepatology 59(5):1761–1771. doi:10.1002/hep.26714
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Kogelman, L.J.A., Kadarmideen, H.N. (2016). Applications of Systems Genetics and Biology for Obesity Using Pig Models. In: Kadarmideen, H. (eds) Systems Biology in Animal Production and Health, Vol. 1. Springer, Cham. https://doi.org/10.1007/978-3-319-43335-6_2
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