A stratified transcriptomics analysis of polygenic Fat and Lean mouse adipose tissues identifies novel candidate obesity genes

PLoS ONE

Volumn 6, Issue 9, 2011, Pages

  Morton, Nicholas M ^a   Nelson, Yvonne B ^a   Michailidou, Zoi ^b   Rollo, Emma M ^a   Ramage, Lynne ^a   Hadoke, Patrick W F ^a   Seckl, Jonathan R ^a   Bunger, Lutz ^c   Horvat, Simon ^d   Kenyon, Christopher J ^a   Dunbar, Donald R ^a  

^a UNIVERSITY OF EDINBURGH   (United Kingdom)

^b UNIVERSITY OF EDINBURGH   (United Kingdom)

^c SCOTTISH AGRICULTURAL COLLEGE   (United Kingdom)

^d UNIVERSITY OF LJUBLJANA   (Slovenia)

Author keywords

[No Author keywords available]

Indexed keywords

ANGIOPOIETIN 1; ANGIOPOIETIN 2; APIN PROTEIN; ARYLDIALKYLPHOSPHATASE 1; ATRIAL NATRIURETIC FACTOR; GELATINASE B; GENE PRODUCT; GLYCOGEN; GLYCOGEN SYNTHASE; GLYCOGEN SYNTHASE 2; HYPOXIA INDUCIBLE FACTOR 1ALPHA; HYPOXIA INDUCIBLE FACTOR 2ALPHA; INTERLEUKIN 8; LACTATE DEHYDROGENASE; LACTATE DEHYDROGENASE 2; MACROPHAGE INFLAMMATORY PROTEIN 1ALPHA; NATRIURETIC PEPTIDE RECEPTOR A; NATRIURETIC PEPTIDE RECEPTOR C; PYRUVATE DEHYDROGENASE; PYRUVATE DEHYDROGENASE 4; RANTES; RETINOL BINDING PROTEIN; RETINOL BINDING PROTEIN 4; RETINOL BINDING PROTEIN 7; THROMBOSPONDIN 1; TRANSCRIPTOME; UNCLASSIFIED DRUG; UNCOUPLING PROTEIN 1; UNCOUPLING PROTEIN 2; UNCOUPLING PROTEIN 3; COMPLEMENT 1Q RECEPTOR; COMPLEMENT RECEPTOR; FIBROBLAST GROWTH FACTOR; FIBROBLAST GROWTH FACTOR 13; MEMBRANE PROTEIN; PROTEIN; TTC7 PROTEIN, MOUSE;

ADIPOCYTE; ADIPOSE TISSUE GLYCOGEN CONTENT; AGTRL1 GENE; ANGPT1 GENE; ANGPT2 GENE; ANGPTL4 GENE; ANIMAL CELL; ANIMAL EXPERIMENT; ANIMAL TISSUE; APIN GENE; ARTICLE; BREEDING; C1QR1 GENE; C3AR1 GENE; CARBOHYDRATE METABOLISM; CCL19 GENE; CCL2 GENE; CCL3 GENE; CCL5 GENE; CELL FUNCTION; CONTROLLED STUDY; CR2 GENE; DNA MICROARRAY; DOWN REGULATION; FGF13 GENE; FMR GENE; GENE; GENE EXPRESSION PROFILING; GENE FUNCTION; GENE IDENTIFICATION; GENE INTERACTION; GENE NUMBER; GLYCOGEN ANALYSIS; GYS2 GENE; HIF1ALPHA GENE; HIF2ALPHA GENE; INTERLEUKIN 8 GENE; KIDNEY PARENCHYMA; LDH2 GENE; LEAN BODY WEIGHT; LIPID DIET; LIPID STORAGE; LIPOLYSIS; LIVER; MALE; MATRIX METALLOPROTEINASE 9 GENE; MOUSE; MOUSE STRAIN; MUSCLE TISSUE; NONHUMAN; NP3R GENE; OBESITY; PDK4 GENE; PLA2G7 GENE; PON1 GENE; PPP1R3D GENE; PROTEIN BLOOD LEVEL; PTGDS2 GENE; QUANTITATIVE ANALYSIS; QUANTITATIVE TRAIT LOCUS; REAL TIME POLYMERASE CHAIN REACTION; RETINOL BINDING PROTEIN 4 GENE; RETINOL BINDING PROTEIN 7 GENE; SAA3 GENE; SELECTIVE BREEDING; SNAP SHOT POOLED TRANSCRIPTOME MICROARRAY; SPP1 GENE; STRAIN DIFFERENCE; SUBCUTANEOUS FAT; TBAXS1 GENE; THBS1 GENE; TISSUE SPECIFICITY; TLR 13 GENE; TLR 2 GENE; TMEPAI GENE; TRP53INP2 GENE; TTC7B GENE; TUBA1A GENE; UNCOUPLING PROTEIN 1 GENE; UNCOUPLING PROTEIN 2 GENE; UNCOUPLING PROTEIN 3 GENE; UPREGULATION; WHITE ADIPOSE TISSUE; ADIPOSE TISSUE; ANIMAL; BIOLOGY; CELL STRAIN 3T3; GENETICS; METABOLISM;

STEATOMYS PRATENSIS;

3T3-L1 CELLS; ADIPOSE TISSUE; ANIMALS; COMPUTATIONAL BIOLOGY; FIBROBLAST GROWTH FACTORS; GLYCOGEN; MEMBRANE GLYCOPROTEINS; MICE; OBESITY; OLIGONUCLEOTIDE ARRAY SEQUENCE ANALYSIS; PROTEINS; QUANTITATIVE TRAIT LOCI; REAL-TIME POLYMERASE CHAIN REACTION; RECEPTORS, COMPLEMENT; TRANSCRIPTOME;

EID: 80052544722     PISSN: None     EISSN: 19326203     Source Type: Journal    
DOI: 10.1371/journal.pone.0023944     Document Type: Article

References (70)

1. McCarthy MI, (2010) Genomics, type 2 diabetes, and obesity. N Engl J Med 363: 2339-50.
2. Herrera BM, Lindgren CM, (2010) The genetics of obesity. Curr Diab Rep 10: 498-505.
3. Franks PW, Poveda A, (2010) Gene-Lifestyle and Gene-Pharmacotherpy Interactions in Obesity and Its Cardiovascular Consequences. Curr Vasc Pharmacol Dec 14 [Epub ahead of print].
4. Bünger L, Hill WG, (1999) Inbred lines of mice derived from long-term divergent selection on fat content and body weight. Mamm Genome 10: 645-8.
5. Horvat S, Bünger L, Falconer VM, Mackay P, Law A, et al. (2000) Mapping of obesity QTLs in a cross between mouse lines divergently selected on fat content. Mamm Genome 11: 2-7.
6. Bünger L, Forsting J, McDonald KL, Horvat S, Duncan J, et al. (2003) Long-term divergent selection on fatness in mice indicates a regulation system independent of leptin production and reception. FASEB J 17: 85-7.
7. Simoncic M, Horvat S, Stevenson PL, Bünger L, Holmes MC, et al. (2008) Divergent physical activity and novel alternative responses to high fat feeding in polygenic fat and lean mice. Behav Genet 38: 292-300.
8. Xu J, Lee WN, Phan J, Saad MF, Reue K, et al. (2006) Lipin deficiency impairs diurnal metabolic fuel switching. Diabetes 55: 3429-38.
9. Ziouzenkova O, Orasanu G, Sharlach M, Akiyama TE, Berger JP, et al. (2007) Retinaldehyde represses adipogenesis and diet-induced obesity. Nat Med 13: 695-702.
10. Jaworski K, Ahmadian M, Duncan RE, Sarkadi-Nagy E, Varady KA, et al. (2009) AdPLA ablation increases lipolysis and prevents obesity induced by high-fat feeding or leptin deficiency. Nat Med 15: 159-68.
11. Lindgren CM, Heid IM, Randall JC, Lamina C, Steinthorsdottir V, et al. (2009) Genome-wide association scan meta-analysis identifies three Loci influencing adiposity and fat distribution. PLoS Genet 5 (6): e1000508.
12. Speliotes EK, Willer CJ, Berndt SI, Monda KL, Thorleifsson G, et al. (2010) Nat Genet 42: 937-48.
13. Morton NM, Densmore V, Wamil M, Ramage L, Nichol K, et al. (2005) A polygenic model of the metabolic syndrome with reduced circulating and intra-adipose glucocorticoid action. Diabetes 54: 3371-8.
14. Speakman JR, (2007) A nonadaptive scenario explaining the genetic predisposition to obesity: the "predation release" hypothesis. Cell Metab 6: 5-12.
15. Stylianou IM, Christians JK, Keightley PD, Bünger L, Clinton M, et al. (2004) Genetic complexity of an obesity QTL (Fob3) revealed by detailed genetic mapping. Mamm Genome 15: 472-81.
16. Stylianou IM, Clinton M, Keightley PD, Pritchard C, Tymowska-Lalanne Z, et al. (2005) Microarray gene expression analysis of the Fob3b obesity QTL identifies positional candidate gene Sqle and perturbed cholesterol and glycolysis pathways. Physiol Genomics 20: 224-32.
17. Peterson TR, Laplante M, Thoreen CC, Sancak Y, Kang SA, (2009) DEPTOR is an mTOR inhibitor frequently overexpressed in multiple myeloma cells and required for their survival. Cell 137: 873-86.
18. Xu H, Barnes GT, Yang Q, Tan G, Yang D, et al. (2003) Chronic inflammation in fat plays a crucial role in the development of obesity-related insulin resistance. J Clin Invest 112: 1821-1830.
19. Mamane Y, Chung Chan C, Lavallee G, Morin N, Xu LJ, et al. (2009) The C3a anaphylatoxin receptor is a key mediator of insulin resistance and functions by modulating adipose tissue macrophage infiltration and activation. Diabetes 58: 2006-17.
20. Sartipy P, Loskutoff DJ, (2003) Monocyte chemoattractant protein 1 in obesity and insulin resistance. Proc Natl Acad Sci USA 100: 7265-7270.
21. Nomiyama T, Perez-Tilve D, Ogawa D, Gizard F, Zhao Y, et al. (2007) Osteopontin mediates obesity-induced adipose tissue macrophage infiltration and insulin resistance in mice. J Clin Invest 117: 2877-88.
22. Shi H, Kokoeva MV, Inouye K, Tzameli I, Yin H, et al. (2006) TLR4 links innate immunity and fatty acid-induced insulin resistance. J Clin Invest 116: 3015-25.
23. Tabeta K, Georgel P, Janssen E, Du X, Hoebe K, et al. (2004) Toll-like receptors 9 and 3 as essential components of innate immune defense against mouse cytomegalovirus infection. Proc Natl Acad Sci U S A 101: 3516-21.
24. Schäffler A, Schölmerich J, Salzberger B, (2007) Adipose tissue as an immunological organ: Toll-like receptors, C1q/TNFs and CTRPs. Trends Immunol 28: 393-9.
25. Wu H, Ghosh S, Perrard XD, Feng L, Garcia GE, (2007) T-cell accumulation and regulated on activation, normal T cell expressed and secreted upregulation in adipose tissue in obesity. Circulation 115: 1029-1038.
26. Roozendaal R, Carroll MC, (2007) Complement receptors CD21 and CD35 in humoral immunity. Immunol Rev 219: 157-66.
27. Han CY, Subramanian S, Chan CK, Omer M, Chiba T, (2007) Adipocyte-derived serum amyloid A3 and hyaluronan play a role in monocyte recruitment and adhesion. Diabetes 56: 2260-73.
28. Kozak LP, Anunciado-Koza R, (2008) UCP1: its involvement and utility in obesity. Int J Obes (Lond) 32: S32-8.
29. Simoncic M, Rezen T, Juvan P, Rozman D, Fazarinc G, (2011) Obesity resistant mechanisms in the Lean polygenic mouse model as indicated by liver transcriptome and expression of selected genes in skeletal muscle. BMC Genomics 12: 96.
30. Yang Q, Graham TE, Mody N, Preitner F, Peroni OD, et al. (2005) Serum retinol binding protein 4 contributes to insulin resistance in obesity and type 2 diabetes. Nature 436: 356-62.
31. Ferretti G, Bacchetti T, Masciangelo S, Bicchiega V, (2010) HDL-paraoxonase and membrane lipid peroxidation: a comparison between healthy and obese subjects. Obesity (Silver Spring) 18: 1079-84.
32. Zhang X, Lam KS, Ye H, Chung SK, Zhou M, (2010) Adipose tissue-specific inhibition of hypoxia inducible factor 1{alpha} induces obesity and glucose intolerance by impeding energy expenditure in mice. J Biol Chem 285: 32869-77.
33. Bruun JM, Lihn AS, Madan AK, Pedersen SB, Schiøtt KM, et al. (2004) Higher production of IL-8 in visceral vs. subcutaneous adipose tissue. Implication of nonadipose cells in adipose tissue. Am J Physiol Endocrinol Metab 286: E8-13.
34. Koch AE, Polverini PJ, Kunkel SL, Harlow LA, DiPietro LA, et al. (1992) Interleukin-8 as a macrophage-derived mediator of angiogenesis. Science 258: 1798-801.
35. O'Hara A, Lim FL, Mazzatti DJ, Trayhurn P, (2009) Microarray analysis identifies matrix metalloproteinases (MMPs) as key genes whose expression is up-regulated in human adipocytes by macrophage-conditioned medium. Pflugers Arch 458: 1103-14.
36. Koppo K, Larrouy D, Marques MA, Berlan M, Bajzova M, et al. (2010) Lipid mobilization in subcutaneous adipose tissue during exercise in lean and obese humans. Roles of insulin and natriuretic peptides. Am J Physiol Endocrinol Metab 299: E258-65.
37. Sengenes C, Zakaroff-Girard A, Moulin A, Berlan M, Bouloumie A, et al. (2002) Natriuretic peptide-dependent lipolysis in fat cells is a primate specificity. Am J Physiol Regul Integr Comp Physiol 283: R257-265.
38. Sabbatini ME, Villagra A, Davio CA, Vatta MS, Fernandez BE, et al. (2003) Atrial natriuretic factor stimulates exocrine pancreatic secretion in the rat through NPR-C receptors. Am J Physiol Gastrointest Liver Physiol 285: G929-37.
39. Cao Y, (2010) Adipose tissue angiogenesis as a therapeutic target for obesity and metabolic diseases. Nat Rev Drug Discov 9: 107-15.
40. Varma V, Yao-Borengasser A, Bodles AM, Rasouli N, Phanavanh B, et al. (2008) Thrombospondin-1 is an adipokine associated with obesity, adipose inflammation, and insulin resistance. Diabetes 57: 432-9.
41. Haviv F, Bradley MF, Kalvin DM, Schneider AJ, Davidson DJ, et al. (2005) Thrombospondin-1 mimetic peptide inhibitors of angiogenesis and tumor growth: design, synthesis, and optimization of pharmacokinetics and biological activities. J Med Chem 48: 2838-46.
42. Aitman TJ, Glazier AM, Wallace CA, Cooper LD, Norsworthy PJ, et al. (1999) Identification of Cd36 (Fat) as an insulin-resistance gene causing defective fatty acid and glucose metabolism in hypertensive rats. Nat Genet 21: 76-83.
43. Gregor MF, Hotamisligil GS, (2010) Inflammatory Mechanisms in Obesity. Annu Rev Immunol DOI:10.1146/annurev-immunol-031210-101322.
44. Rutkowski JM, Davis KE, Scherer PE, (2009) Mechanisms of obesity and related pathologies: the macro- and microcirculation of adipose tissue. FEBS J 276: 5738-46.
45. Wood IS, de Heredia FP, Wang B, Trayhurn P, (2009) Cellular hypoxia and adipose tissue dysfunction in obesity. Proc Nutr Soc 2009 68: 370-7.
46. Kim YJ, Park T, (2008) Genes are differentially expressed in the epididymal fat of rats rendered obese by a high-fat diet. Nutr Res 28: 414-22.
47. Kleemann R, van Erk M, Verschuren L, van den Hoek AM, Koek M, (2010) Time-resolved and tissue-specific systems analysis of the pathogenesis of insulin resistance. PLoS One 5 (1): e8817.
48. Mejhert N, Galitzky J, Pettersson AT, Bambace C, Blomqvist L, et al. (2010) Mapping of the fibroblast growth factors in human white adipose tissue. J Clin Endocrinol Metab 95: 2451-7.
49. Bourdon C, Hojna S, Jordan M, Bérubé J, Kren V, et al. (2009) Genetic locus on rat chromosome 20 regulates diet-induced adipocyte hypertrophy: a microarray gene expression study. Physiol Genomics 38: 63-72.
50. Keller MP, Attie AD, (2010) Physiological insights gained from gene expression analysis in obesity and diabetes. Annu Rev Nutr 30: 341-64.
51. Wolfs MG, Rensen SS, Bruin-Van Dijk EJ, Verdam FJ, Greve JW, et al. (2010) Co-expressed immune and metabolic genes in visceral and subcutaneous adipose tissue from severely obese individuals are associated with plasma HDL and glucose levels: a microarray study. BMC Med Genomics 3: 34.
52. Grove KL, Fried SK, Greenberg AS, Xiao XQ, Clegg DJ, (2010) A microarray analysis of sexual dimorphism of adipose tissues in high-fat-diet-induced obese mice. Int J Obes (Lond) 34: 989-1000.
53. Adams JC, Lawler J, (2004) The thrombospondins. Int J Biochem Cell Biol 36: 961-8.
54. Dankel SN, Fadnes DJ, Stavrum AK, Stansberg C, Holdhus R, et al. (2010) Switch from stress response to homeobox transcription factors in adipose tissue after profound fat loss. PLoS One 5: e11033.
55. Chiu S, Kim K, Haus KA, Espinal GM, Millon LV, et al. (2007) Identification of positional candidate genes for body weight and adiposity in subcongenic mice. Physiol Genomics 31: 75-85.
56. Wallingford N, Perroud B, Gao Q, Coppola A, Gyengesi E, et al. (2009) Prolylcarboxypeptidase regulates food intake by inactivating alpha-MSH in rodents. J Clin Invest 119: 2291-2303.
57. Yalcin B, Willis-Owen SA, Fullerton J, Meesaq A, Deacon RM, et al. (2004) Genetic dissection of a behavioral quantitative trait locus shows that Rgs2 modulates anxiety in mice. Nat Genet 36: 1197-202.
58. Weedon MN, Frayling TM, (2008) Reaching new heights: insights into the genetics of human stature. Trends Genet 24: 595-603.
59. Green H, Meuth M, (1974) An established pre-adipose cell line and its differentiation in culture. Cell 3: 127-33.
60. Passonneau JV, Lauderdale VR, (1974) A comparison of three methods of glycogen measurement in tissues. Anal Biochem 60: 405-12.
61. Delibegovic M, Armstrong CG, Dobbie L, Watt PW, Smith AJ, et al. (2003) Disruption of the striated muscle glycogen targeting subunit PPP1R3A of protein phosphatase 1 leads to increased weight gain, fat deposition, and development of insulin resistance. Diabetes 52: 596-604.
62. Collier A, Ghosh S, McGlynn B, Hollins G, (2011) Prostate Cancer, Androgen Deprivation Therapy, Obesity, the Metabolic Syndrome, Type 2 Diabetes, and Cardiovascular Disease: A Review. Am J Clin Oncol [Epub ahead of print].
63. Minamino T, Orimo M, Shimizu I, Kunieda T, Yokoyama M, et al. (2009) A crucial role for adipose tissue p53 in the regulation of insulin resistance. Nat Med 15: 1082-7.
64. Häder T, Müller S, Aguilera M, Eulenberg KG, Steuernagel A, et al. (2003) Control of triglyceride storage by a WD40/TPR-domain protein. EMBO Rep 4: 511-6.
65. Brasaemle DL, Dolios G, Shapiro L, Wang R, (2004) Proteomic analysis of proteins associated with lipid droplets of basal and lipolytically stimulated 3T3-L1 adipocytes. J Biol Chem 279: 46835-42.
66. Kliewer SA, Mangelsdorf DJ, (2010) Fibroblast growth factor 21: from pharmacology to physiology. Am J Clin Nutr 91: 254S-257S.
67. Perrini S, Cignarelli A, Ficarella R, Laviola L, Giorgino F, (2009) Human adipose tissue precursor cells: a new factor linking regulation of fat mass to obesity and type 2 diabetes? Arch Physiol Biochem 115: 218-26.
68. de Vries BB, Fryns JP, Butler MG, Canziani F, Wesby-van Swaay E, et al. (1993) Clinical and molecular studies in fragile X patients with a Prader-Willi-like phenotype. J Med Genet 30: 761-6.
69. Schrander-Stumpel C, Gerver WJ, Meyer H, Engelen J, Mulder H, (1994) Prader-Willi-like phenotype in fragile X syndrome. Clin Genet 45: 175-80.
70. Naggert J, Svenson KL, Smith RV, Paigen B, Peters LL, (2011) Diet effects on bone mineral density and content, body composition, and plasma glucose, leptin, and insulin levels in 43 inbred strains of mice on a high-fat atherogenic diet. MPD: Naggert1. Mouse Phenome Database web site, The Jackson Laboratory, Bar Harbor, Maine USA.http://phenome.jax.org.