Targeting PPAR? in the epigenome rescues genetic metabolic defects in mice

Journal of Clinical Investigation

Volumn 127, Issue 4, 2017, Pages 1451-1462

  Soccio, Raymond E ^a,b   Li, Zhenghui ^a,b   Chen, Eric R ^a,b   Foong, Yee Hoon ^a,b   Benson, Kiara K ^a,b   Dispirito, Joanna R ^a,b   Mullican, Shannon E ^a,b   Emmett, Matthew J ^a,b   Briggs, Erika R ^a,b   Peed, Lindsey C ^a,b   Dzeng, Richard K ^a,b   Medina, Carlos J ^a,b   Jolivert, Jennifer F ^a,b   Kissig, Megan ^b,c   Rajapurkar, Satyajit R ^a,b   Damle, Manashree ^a,b   Lim, Hee Woong ^b,d   Won, Kyoung Jae ^b,d   Seale, Patrick ^b,c   Steger, David J ^a,b   Lazar, Mitchell A ^a,b   more..

^a Department of Medicine   (United States)

^b Institute for Diabetes Obesity and Metabolism   (United States)

^c Perelman School of Medicine at the University of Pennsylvania ^*  (United States)

^d UNIVERSITY OF PENNSYLVANIA   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

INSULIN; PEROXISOME PROLIFERATOR ACTIVATED RECEPTOR GAMMA; ROSIGLITAZONE; UNCOUPLING PROTEIN 1; 2,4 THIAZOLIDINEDIONE DERIVATIVE; ANTIDIABETIC AGENT; PROTEIN BINDING; TRANSCRIPTOME; UCP1 PROTEIN, MOUSE;

ALLELE; ANIMAL EXPERIMENT; ANIMAL MODEL; ANIMAL TISSUE; ARTICLE; BROWN ADIPOSE TISSUE; CONTROLLED STUDY; DIET INDUCED OBESITY; EPIGENETICS; GENE; GENE EXPRESSION; GENE LOCUS; INGUINAL FAT; INSULIN SENSITIVITY; LIPID DIET; MOUSE; MOUSE MODEL; NONHUMAN; PRIORITY JOURNAL; SUBCUTANEOUS FAT; UCP1 GENE; WHITE ADIPOSE TISSUE; 129 MOUSE; ABDOMINAL SUBCUTANEOUS FAT; ADVERSE EFFECTS; ANIMAL; C57BL MOUSE; GENETIC EPIGENESIS; GENETICS; INTRAABDOMINAL FAT; MALE; METABOLISM; OBESITY; PHYSIOLOGY; REGULATORY SEQUENCE; TRANSCRIPTION INITIATION;

ANIMALS; DIET, HIGH-FAT; EPIGENESIS, GENETIC; HYPOGLYCEMIC AGENTS; INTRA-ABDOMINAL FAT; MALE; MICE, 129 STRAIN; MICE, INBRED C57BL; OBESITY; PPAR GAMMA; PROTEIN BINDING; REGULATORY ELEMENTS, TRANSCRIPTIONAL; SUBCUTANEOUS FAT, ABDOMINAL; THIAZOLIDINEDIONES; TRANSCRIPTIONAL ACTIVATION; TRANSCRIPTOME; UNCOUPLING PROTEIN 1;

EID: 85018709588     PISSN: 00219738     EISSN: 15588238     Source Type: Journal    
DOI: 10.1172/JCI91211     Document Type: Article

References (84)

1. Hardy OT, Czech MP, Corvera S. What causes the insulin resistance underlying obesity? Curr Opin Endocrinol Diabetes Obes. 2012;19(2):81-87.
2. Iozzo P. Viewpoints on the Way to the Consensus Session: where does insulin resistance start? The adipose tissue. Diabetes Care. 2009; 32(suppl 2):S168-S173.
3. Montague CT, O'Rahilly S. The perils of portliness: causes and consequences of visceral adiposity. Diabetes. 2000;49(6):883-888.
4. Ravussin E, Tataranni PA. Dietary fat and human obesity. J Am Diet Assoc. 1997;97(7 suppl):S42-S46.
5. Hariri N, Thibault L. High-fat diet-induced obesity in animal models. Nutr Res Rev. 2010;23(2):270-299.
6. Almind K, Kahn CR. Genetic determinants of energy expenditure and insulin resistance in diet-induced obesity in mice. Diabetes. 2004;53(12):3274-3285.
7. Gallou-Kabani C, et al. C57BL/6J and A/J mice fed a high-fat diet delineate components of metabolic syndrome. Obesity (Silver Spring). 2007;15(8):1996-2005.
8. West DB, Waguespack J, McCollister S. Dietary obesity in the mouse: interaction of strain with diet composition. Am J Physiol. 1995; 268(3 pt 2):R658-R665.
9. Lin C, et al. QTL analysis of dietary obesity in C57BL/6byj X 129P3/J F2 mice: diet-and sex-dependent effects. PLoS One. 2013;8(7):e68776.
10. Su Z, Korstanje R, Tsaih SW, Paigen B. Candidate genes for obesity revealed from a C57BL/6J x 129S1/SvImJ intercross. Int J Obes (Lond). 2008;32(7):1180-1189.
11. Parks BW, et al. Genetic control of obesity and gut microbiota composition in response to high-fat, high-sucrose diet in mice. Cell Metab. 2013;17(1):141-152.
12. DeClercq VC, Goldsby JS, McMurray DN, Chapkin RS. Distinct adipose depots from mice differentially respond to a high-fat, high-salt diet. J Nutr. 2016;146(6):1189-1196.
13. Weisberg SP, McCann D, Desai M, Rosenbaum M, Leibel RL, Ferrante AW. Obesity is associated with macrophage accumulation in adipose tissue. J Clin Invest. 2003;112(12):1796-1808.
14. Choi M-S, et al. High-fat diet decreases energy expenditure and expression of genes controlling lipid metabolism, mitochondrial function and skeletal system development in the adipose tissue, along with increased expression of extracellular matrix remodelling-and inflammation-related genes. Br J Nutr. 2015;113(6):867-877.
15. Nadler ST, Stoehr JP, Schueler KL, Tanimoto G, Yandell BS, Attie AD. The expression of adipogenic genes is decreased in obesity and diabetes mellitus. Proc Natl Acad Sci U S A. 2000;97(21):11371-11376.
16. Voigt A, Agnew K, van Schothorst EM, Keijer J, Klaus S. Short-term, high fat feeding-induced changes in white adipose tissue gene expression are highly predictive for long-term changes. Mol Nutr Food Res. 2013;57(8):1423-1434.
17. Lehrke M, Lazar MA. The many faces of PPAR?. Cell. 2005;123(6):993-999.
18. Soccio RE, Chen ER, Lazar MA. Thiazolidinediones and the promise of insulin sensitization in type 2 diabetes. Cell Metab. 2014;20(4):573-591.
19. Tomas J, et al. High-fat diet modifies the PPAR-? pathway leading to disruption of microbial and physiological ecosystem in murine small intestine. Proc Natl Acad Sci U S A. 2016;113(40):E5934-E5943.
20. Stienstra R, Duval C, Keshtkar S, van der Laak J, Kersten S, Müller M. Peroxisome proliferator-activated receptor gamma activation promotes infiltration of alternatively activated macrophages into adipose tissue. J Biol Chem. 2008;283(33):22620-22627.
21. Harms M, Seale P. Brown and beige fat: development, function and therapeutic potential. Nat Med. 2013;19(10):1252-1263.
22. Meierhofer D, Weidner C, Sauer S. Integrative analysis of transcriptomics, proteomics, and metabolomics data of white adipose and liver tissue of high-fat diet and rosiglitazone-treated insulin-resistant mice identified pathway alterations and molecular hubs. J Proteome Res. 2014;13(12):5592-5602.
23. Rong JX, et al. Adipose mitochondrial biogenesis is suppressed in db/db and high-fat diet-fed mice and improved by rosiglitazone. Diabetes. 2007;56(7):1751-1760.
24. Callinan PA, Feinberg AP. The emerging science of epigenomics. Hum Mol Genet. 2006; 15(suppl 1):R95-R101.
25. Leung A, et al. Open chromatin profiling in mice livers reveals unique chromatin variations induced by high fat diet. J Biol Chem. 2014;289(34):23557-23567.
26. Kang S, et al. Identification of nuclear hormone receptor pathways causing insulin resistance by transcriptional and epigenomic analysis. Nat Cell Biol. 2015;17(1):44-56.
27. Heinz S, et al. Simple combinations of lineage-determining transcription factors prime cis-regulatory elements required for macrophage and B cell identities. Mol Cell. 2010;38(4):576-589.
28. Pedersen DJ, et al. A major role of insulin in promoting obesity-associated adipose tissue inflammation. Mol Metab. 2015;4(7):507-518.
29. Lumeng CN, Deyoung SM, Bodzin JL, Saltiel AR. Increased inflammatory properties of adipose tissue macrophages recruited during diet-induced obesity. Diabetes. 2007;56(1):16-23.
30. Lefterova MI, et al. Cell-specific determinants of peroxisome proliferator-activated receptor gamma function in adipocytes and macrophages. Mol Cell Biol. 2010;30(9):2078-2089.
31. Xu H, et al. Chronic inflammation in fat plays a crucial role in the development of obesity-related insulin resistance. J Clin Invest. 2003;112(12):1821-1830.
32. Deng T, et al. Class II major histocompatibility complex plays an essential role in obesity-induced adipose inflammation. Cell Metab. 2013;17(3):411-422.
33. Straus DS, Glass CK. Anti-inflammatory actions of PPAR ligands: new insights on cellular and molecular mechanisms. Trends Immunol. 2007;28(12):551-558.
34. Wilson-Fritch L, et al. Mitochondrial remodeling in adipose tissue associated with obesity and treatment with rosiglitazone. J Clin Invest. 2004;114(9):1281-1289.
35. Wu J, et al. Beige adipocytes are a distinct type of thermogenic fat cell in mouse and human. Cell. 2012;150(2):366-376.
36. Vitali A, Murano I, Zingaretti MC, Frontini A, Ricquier D, Cinti S. The adipose organ of obesity-prone C57BL/6J mice is composed of mixed white and brown adipocytes. J Lipid Res. 2012;53(4):619-629.
37. Kozak LP, Anunciado-Koza R. UCP1: its involvement and utility in obesity. Int J Obes (Lond). 2008;32(suppl 7):S32-S38.
38. Norton N, et al. Universal, robust, highly quantitative SNP allele frequency measurement in DNA pools. Hum Genet. 2002;110(5):471-478.
39. Soccio RE, et al. Genetic variation determines PPAR? function and anti-diabetic drug response in vivo. Cell. 2015;162(1):33-44.
40. Haakonsson AK, Stahl Madsen M, Nielsen R, Sandelin A, Mandrup S. Acute genome-wide effects of rosiglitazone on PPAR? transcriptional networks in adipocytes. Mol Endocrinol. 2013;27(9):1536-1549.
41. Step SE, et al. Anti-diabetic rosiglitazone remodels the adipocyte transcriptome by redistributing transcription to PPAR?-driven enhancers. Genes Dev. 2014;28(9):1018-1028.
42. Kozak LP. The genetics of brown adipocyte induction in white fat depots. Front Endocrinol (Lausanne). 2011;2:64.
43. Di Mascolo D, et al. Rosiglitazone-loaded nanospheres for modulating macrophage-specific inflammation in obesity. J Control Release. 2013;170(3):460-468.
44. Jilkova ZM, et al. Adipose tissue-related proteins locally associated with resolution of inflammation in obese mice. Int J Obes (Lond). 2014;38(2):216-223.
45. Nguyen MT, et al. Regulation of chemokine and chemokine receptor expression by PPAR? in adipocytes and macrophages. PLoS One. 2012;7(4):e34976.
46. Kraakman MJ, et al. Blocking IL-6 trans-signaling prevents high-fat diet-induced adipose tissue macrophage recruitment but does not improve insulin resistance. Cell Metab. 2015;21(3):403-416.
47. Olefsky JM, Glass CK. Macrophages, inflammation, and insulin resistance. Annu Rev Physiol. 2010;72:219-246.
48. Marathe C et al. Preserved glucose tolerance in high-fat-fed C57BL/6 mice transplanted with PPAR?-/-, PPAR?-/-, PPAR-/-, or LXR-/-bone marrow. J Lipid Res. 2009;50(2):214-224.
49. Blüher M. Adipose tissue inflammation: a cause or consequence of obesity-related insulin resistance? Clin Sci Lond Engl. 2016;130(18):1603-1614.
50. Zhang B, et al. Negative regulation of peroxisome proliferator-activated receptor-? gene expression contributes to the antiadipogenic effects of tumor necrosis factor-?. Mol Endocrinol. 1996;10(11):1457-1466.
51. Jang MK, Jung MH. ATF3 represses PPAR? expression and inhibits adipocyte differentiation. Biochem Biophys Res Commun. 2014;454(1):58-64.
52. Ohno H, Shinoda K, Spiegelman BM, Kajimura S. PPAR? agonists induce a white-to-brown fat conversion through stabilization of PRDM16 protein. Cell Metab. 2012;15(3):395-404.
53. Walker GE, et al. Subcutaneous abdominal adipose tissue subcompartments: potential role in rosiglitazone effects. Obesity (Silver Spring). 2008;16(9):1983-1991.
54. Wang W, Seale P. Control of brown and beige fat development. Nat Rev Mol Cell Biol. 2016;17(11):691-702.
55. Guerra C, Koza RA, Yamashita H, Walsh K, Kozak LP. Emergence of brown adipocytes in white fat in mice is under genetic control. Effects on body weight and adiposity. J Clin Invest. 1998;102(2):412-420.
56. Shabalina IG, Petrovic N, de Jong JM, Kalinovich AV, Cannon B, Nedergaard J. UCP1 in brite/beige adipose tissue mitochondria is functionally thermogenic. Cell Rep. 2013;5(5):1196-1203.
57. Xue B, Rim JS, Hogan JC, Coulter AA, Koza RA, Kozak LP. Genetic variability affects the development of brown adipocytes in white fat but not in interscapular brown fat. J Lipid Res. 2007;48(1):41-51.
58. Coulter AA, Bearden CM, Liu X, Koza RA, Kozak LP. Dietary fat interacts with QTLs controlling induction of Pgc-1? and Ucp1 during conversion of white to brown fat. Physiol Genomics. 2003;14(2):139-147.
59. Seale P, et al. PRDM16 controls a brown fat/skeletal muscle switch. Nature. 2008;454(7207):961-967.
60. Koza RA, Hohmann SM, Guerra C, Rossmeisl M, Kozak LP. Synergistic gene interactions control the induction of the mitochondrial uncoupling protein (Ucp1) gene in white fat tissue. J Biol Chem. 2000;275(44):34486-34492.
61. Li Y, Bolze F, Fromme T, Klingenspor M. Intrinsic differences in BRITE adipogenesis of primary adipocytes from two different mouse strains. Biochim Biophys Acta. 2014;1841(9):1345-1352.
62. Esterbauer H, et al. Uncoupling protein-1 mRNA expression in obese human subjects: the role of sequence variations at the uncoupling protein-1 gene locus. J Lipid Res. 1998;39(4):834-844.
63. Fumeron F, et al. Polymorphisms of uncoupling protein (UCP) and beta 3 adrenoreceptor genes in obese people submitted to a low calorie diet. Int J Obes Relat Metab Disord. 1996;20(12):1051-1054.
64. Heilbronn LK, Kind KL, Pancewicz E, Morris AM, Noakes M, Clifton PM. Association of-3826 G variant in uncoupling protein-1 with increased BMI in overweight Australian women. Diabetologia. 2000;43(2):242-244.
65. Kim KS, et al. The finding of new genetic polymorphism of UCP-1 A-1766G and its effects on body fat accumulation. Biochim Biophys Acta. 2005;1741(1-2):149-155.
66. Nicoletti CF, et al. UCP1-3826 A>G polymorphism affects weight, fat mass, and risk of type 2 diabetes mellitus in grade III obese patients. Nutrition. 2016;32(1):83-87.
67. Nagai N, Sakane N, Tsuzaki K, Moritani T. UCP1 genetic polymorphism (-3826 A/G) diminishes resting energy expenditure and thermoregulatory sympathetic nervous system activity in young females. Int J Obes (Lond). 2011;35(8):1050-1055.
68. Yoneshiro T, et al. Impact of UCP1 and ?3AR gene polymorphisms on age-related changes in brown adipose tissue and adiposity in humans. Int J Obes (Lond). 2013;37(7):993-998.
69. Rose G, Crocco P, D'Aquila P, Montesanto A, Bellizzi D, Passarino G. Two variants located in the upstream enhancer region of human UCP1 gene affect gene expression and are correlated with human longevity. Exp Gerontol. 2011;46(11):897-904.
70. Brondani LA, Assmann TS, de Souza BM, Bouças AP, Canani LH, Crispim D. Meta-analysis reveals the association of common variants in the uncoupling protein (UCP) 1-3 genes with body mass index variability. PLoS One. 2014;9(5):e96411.
71. Fall T, Ingelsson E. Genome-wide association studies of obesity and metabolic syndrome. Mol Cell Endocrinol. 2014;382(1):740-757.
72. Deplancke B, Alpern D, Gardeux V. The genetics of transcription factor DNA binding variation. Cell. 2016;166(3):538-554.
73. Langmead B, Trapnell C, Pop M, Salzberg SL. Ultrafast and memory-efficient alignment of short DNA sequences to the human genome. Genome Biol. 2009;10(3):R25.
74. Saldanha AJ. Java Treeview-extensible visualization of microarray data. Bioinforma Oxf Engl. 2004;20(17):3246-3248.
75. McLean CY, et al. GREAT improves functional interpretation of cis-regulatory regions. Nat Biotechnol. 2010;28(5):495-501.
76. Bailey TL, et al. MEME SUITE: tools for motif discovery and searching. Nucleic Acids Res. 2009;37(Web Server issue):W202-W208.
77. Trapnell C, et al. Differential gene and transcript expression analysis of RNA-seq experiments with TopHat and Cufflinks. Nat Protoc. 2012;7(3):562-578.
78. Anders S, Pyl PT, Huber W. HTSeq-a Python framework to work with high-throughput sequencing data. Bioinforma Oxf Engl. 2015;31(2):166-169.
79. Love MI, Huber W, Anders S. Moderated estimation of fold change and dispersion for RNA-seq data with DESeq2. Genome Biol. 2014;15(12):550.
80. Huang da W, Sherman BT, Lempicki RA. Systematic and integrative analysis of large gene lists using DAVID bioinformatics resources. Nat Protoc. 2009;4(1):44-57.
81. Keane TM, et al. Mouse genomic variation and its effect on phenotypes and gene regulation. Nature. 2011;477(7364):289-294.
82. Li H, et al. The Sequence Alignment/ Map format and SAMtools. Bioinformatics. 2009;25(16):2078-2079.
83. Thorvaldsdóttir H, Robinson JT, Mesirov JP. Integrative Genomics Viewer (IGV): high-performance genomics data visualization and exploration. Brief Bioinformatics. 2013;14(2):178-192.
84. Gerhart-Hines Z, et al. The nuclear receptor Rev-erb? controls circadian thermogenic plasticity. Nature. 2013;503(7476):410-413.