Neuron-specific deletion of peroxisome proliferator-activated receptor delta (PPARδ) in mice leads to increased susceptibility to diet-induced obesity

PLoS ONE

Volumn 7, Issue 8, 2012, Pages

  Kocalis, Heidi E ^a   Turney, Maxine K ^a   Printz, Richard L ^a   Laryea, Gloria N ^a   Muglia, Louis J ^a   Davies, Sean S ^a   Stanwood, Gregg D ^a   McGuinness, Owen P ^a   Niswender, Kevin D ^a,b  

^a VANDERBILT UNIVERSITY SCHOOL OF MEDICINE   (United States)

^b DEPARTMENT OF VETERANS AFFAIRS   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

LEPTIN; NEUROPEPTIDE; PEROXISOME PROLIFERATOR ACTIVATED RECEPTOR ALPHA; PEROXISOME PROLIFERATOR ACTIVATED RECEPTOR DELTA; PEROXISOME PROLIFERATOR ACTIVATED RECEPTOR GAMMA; UNCOUPLING PROTEIN 2;

ANIMAL CELL; ANIMAL TISSUE; ANTHROPOMETRIC PARAMETERS; ARTICLE; BODY COMPOSITION; BODY FAT; CELL SPECIFICITY; CONTROLLED STUDY; DIET; DIET RESTRICTION; DISEASE PREDISPOSITION; FAT MASS; FATTY ACID OXIDATION; FEEDING BEHAVIOR; GENE DELETION; GENE EXPRESSION; GENE EXPRESSION REGULATION; GENE TARGETING; HORMONE RESPONSE; HYPOTHALAMIC INFLAMMATION; HYPOTHALAMUS DISEASE; KNOCKOUT MOUSE; LEAN MASS; LEPTIN RESISTANCE; LIPID DIET; LIPID STORAGE; LOW FAT DIET; MALE; METABOLIC DISORDER; MOUSE; NERVE CELL; NEUROPROTECTION; NONHUMAN; OBESITY; PROTEIN EXPRESSION; PROTEIN FUNCTION; UPREGULATION;

ANIMALS; BODY COMPOSITION; BRAIN; DIET, FAT-RESTRICTED; DIET, HIGH-FAT; EATING; ENERGY METABOLISM; FEMALE; LIPID METABOLISM; MALE; MICE; MICE, KNOCKOUT; OBESITY; PPAR DELTA;

EID: 84865191020     PISSN: None     EISSN: 19326203     Source Type: Journal    
DOI: 10.1371/journal.pone.0042981     Document Type: Article

References (74)

1. Mokdad AH, Ford ES, Bowman BA, Dietz WH, Vinicor F, et al. ((2003)) Prevalence of obesity, diabetes, and obesity-related health risk factors, 2001. JAMA 289:: 76--79.
2. Ogden CL, Carroll MD, Curtin LR, McDowell MA, Tabak CJ, et al. ((2006)) Prevalence of overweight and obesity in the United States, 1999-2004. JAMA 295:: 1549--1555.
3. Porte D Jr, Baskin DG, Schwartz MW, ((2002)) Leptin and insulin action in the central nervous system. Nutr Rev 60:: S20--29; discussion S68-84, 85-27.
4. Blouet C, Schwartz GJ, ((2010)) Hypothalamic nutrient sensing in the control of energy homeostasis. Behav Brain Res 209:: 1--12.
5. Oscai LB, ((1982)) Dietary-induced severe obesity: a rat model. Am J Physiol 242:: R212--215.
6. Bray GA, Popkin BM, ((1998)) Dietary fat intake does affect obesity! Am J Clin Nutr. 68:: 1157--1173.
7. Woods SC, Seeley RJ, Rushing PA, D'Alessio D, Tso P, ((2003)) A controlled high-fat diet induces an obese syndrome in rats. J Nutr 133:: 1081--1087.
8. Maron DJ, Fair JM, Haskell WL, ((1991)) Saturated fat intake and insulin resistance in men with coronary artery disease. The Stanford Coronary Risk Intervention Project Investigators and Staff. Circulation 84:: 2020--2027.
9. Posey KA, Clegg DJ, Printz RL, Byun J, Morton GJ, et al. ((2009)) Hypothalamic proinflammatory lipid accumulation, inflammation, and insulin resistance in rats fed a high-fat diet. Am J Physiol Endocrinol Metab 296:: E1003--1012.
10. De Souza CT, Araujo EP, Bordin S, Ashimine R, Zollner RL, et al. ((2005)) Consumption of a fat-rich diet activates a proinflammatory response and induces insulin resistance in the hypothalamus. Endocrinology 146:: 4192--4199.
11. Speed N, Saunders C, Davis AR, Owens WA, Matthies HJ, et al. ((2011)) Impaired Striatal Akt Signaling Disrupts Dopamine Homeostasis and Increases Feeding. PLoS One 6:: e25169.
12. Thaler JP, Yi CX, Schur EA, Guyenet SJ, Hwang BH, et al. ((2012)) Obesity is associated with hypothalamic injury in rodents and humans. J Clin Invest 122:: 153--162.
13. Issemann I, Green S, ((1990)) Activation of a member of the steroid hormone receptor superfamily by peroxisome proliferators. Nature 347:: 645--650.
14. Dreyer C, Krey G, Keller H, Givel F, Helftenbein G, et al. ((1992)) Control of the peroxisomal beta-oxidation pathway by a novel family of nuclear hormone receptors. Cell 68:: 879--887.
15. Lee CH, Olson P, Evans RM, ((2003)) Minireview: lipid metabolism, metabolic diseases, and peroxisome proliferator-activated receptors. Endocrinology 144:: 2201--2207.
16. Forman BM, Chen J, Evans RM, ((1997)) Hypolipidemic drugs, polyunsaturated fatty acids, and eicosanoids are ligands for peroxisome proliferator-activated receptors alpha and delta. Proc Natl Acad Sci U S A 94:: 4312--4317.
17. Braissant O, Foufelle F, Scotto C, Dauca M, Wahli W, ((1996)) Differential expression of peroxisome proliferator-activated receptors (PPARs): tissue distribution of PPAR-alpha,-beta, and-gamma in the adult rat. Endocrinology 137:: 354--366.
18. Chawla A, Schwarz EJ, Dimaculangan DD, Lazar MA, ((1994)) Peroxisome proliferator-activated receptor (PPAR) gamma: adipose-predominant expression and induction early in adipocyte differentiation. Endocrinology 135:: 798--800.
19. Kersten S, Seydoux J, Peters JM, Gonzalez FJ, Desvergne B, et al. ((1999)) Peroxisome proliferator-activated receptor alpha mediates the adaptive response to fasting. J Clin Invest 103:: 1489--1498.
20. Auwerx J, Schoonjans K, Fruchart JC, Staels B, ((1996)) Transcriptional control of triglyceride metabolism: fibrates and fatty acids change the expression of the LPL and apo C-III genes by activating the nuclear receptor PPAR. Atherosclerosis 124 Suppl: S29--37.
21. Lee SS, Pineau T, Drago J, Lee EJ, Owens JW, et al. ((1995)) Targeted disruption of the alpha isoform of the peroxisome proliferator-activated receptor gene in mice results in abolishment of the pleiotropic effects of peroxisome proliferators. Mol Cell Biol 15:: 3012--3022.
22. Dressel U, Allen TL, Pippal JB, Rohde PR, Lau P, et al. ((2003)) The peroxisome proliferator-activated receptor beta/delta agonist, GW501516, regulates the expression of genes involved in lipid catabolism and energy uncoupling in skeletal muscle cells. Mol Endocrinol 17:: 2477--2493.
23. Wang YX, Zhang CL, Yu RT, Cho HK, Nelson MC, et al. ((2004)) Regulation of muscle fiber type and running endurance by PPARdelta. PLoS Biol 2:: e294.
24. Peters JM, Lee SST, Li W, Ward JM, Gavrilova O, et al. ((2000)) Growth, Adipose, Brain, and Skin Alterations Resulting from Targeted Disruption of the Mouse Peroxisome Proliferator-Activated Receptor beta (delta). Mol Cell Biol 20:: 5119--5128.
25. Miyachi H, ((2007)) Design, synthesis, and structure-activity relationship study of peroxisome proliferator-activated receptor (PPAR) delta-selective ligands. Curr Med Chem 14:: 2335--2343.
26. Yessoufou A, Wahli W, ((2010)) Multifaceted roles of peroxisome proliferator-activated receptors (PPARs) at the cellular and whole organism levels. Swiss Med Wkly 140:: w13071.
27. Bright JJ, Kanakasabai S, Chearwae W, Chakraborty S, ((2008)) PPAR Regulation of Inflammatory Signaling in CNS Diseases. PPAR Res 2008:: 658520.
28. Moreno S, Farioli-Vecchioli S, Ceru MP, ((2004)) Immunolocalization of peroxisome proliferator-activated receptors and retinoid X receptors in the adult rat CNS. Neuroscience 123:: 131--145.
29. Lu M, Sarruf DA, Talukdar S, Sharma S, Li P, et al. ((2011)) Brain PPAR-[gamma] promotes obesity and is required for the insulin-sensitizing effect of thiazolidinediones. Nat Med 17:: 618--622.
30. Ryan KK, Li B, Grayson BE, Matter EK, Woods SC, et al. ((2011)) A role for central nervous system PPAR-gamma in the regulation of energy balance. Nat Med 17:: 623--626.
31. Chakravarthy MV, Zhu Y, Lopez M, Yin L, Wozniak DF, et al. ((2007)) Brain fatty acid synthase activates PPARalpha to maintain energy homeostasis. J Clin Invest 117:: 2539--2552.
32. Xing G, Zhang L, Heynen T, Yoshikawa T, Smith M, et al. ((1995)) Rat PPAR delta contains a CGG triplet repeat and is prominently expressed in the thalamic nuclei. Biochem Biophys Res Commun 217:: 1015--1025.
33. Woods JW, Tanen M, Figueroa DJ, Biswas C, Zycband E, et al. ((2003)) Localization of PPARdelta in murine central nervous system: expression in oligodendrocytes and neurons. Brain Res 975:: 10--21.
34. Kalinin S, Richardson JC, Feinstein DL, ((2009)) A PPARdelta agonist reduces amyloid burden and brain inflammation in a transgenic mouse model of Alzheimer's disease. Curr Alzheimer Res 6:: 431--437.
35. Dunn SE, Bhat R, Straus DS, Sobel RA, Axtell R, et al. ((2010)) Peroxisome proliferator-activated receptor delta limits the expansion of pathogenic Th cells during central nervous system autoimmunity. J Exp Med 207:: 1599--1608.
36. Schnegg CI, Robbins ME, ((2011)) Neuroprotective Mechanisms of PPARdelta: Modulation of Oxidative Stress and Inflammatory Processes. PPAR Res 2011:: 373560.
37. Sauer B, Henderson N, ((1989)) Cre-stimulated recombination at loxP-containing DNA sequences placed into the mammalian genome. Nucleic Acids Res 17:: 147--161.
38. Barak Y, Liao D, He W, Ong ES, Nelson MC, et al. ((2002)) Effects of peroxisome proliferator-activated receptor delta on placentation, adiposity, and colorectal cancer. Proc Natl Acad Sci U S A 99:: 303--308.
39. Dubois NC, Hofmann D, Kaloulis K, Bishop JM, Trumpp A, ((2006)) Nestin-Cre transgenic mouse line Nes-Cre1 mediates highly efficient Cre/loxP mediated recombination in the nervous system, kidney, and somite-derived tissues. Genesis 44:: 355--360.
40. Friedman JM, ((2002)) The function of leptin in nutrition, weight, and physiology. Nutr Rev 60:: S1--14; discussion S68-84, 85-17.
41. Levin BE, Dunn-Meynell AA, ((2002)) Reduced central leptin sensitivity in rats with diet-induced obesity. Am J Physiol Regul Integr Comp Physiol 283:: R941--948.
42. Vaisse C, Halaas JL, Horvath CM, Darnell JE Jr, Stoffel M, et al. ((1996)) Leptin activation of Stat3 in the hypothalamus of wild-type and ob/ob mice but not db/db mice. Nat Genet 14:: 95--97.
43. Georgiadi A, Lichtenstein L, Degenhardt T, Boekschoten MV, van Bilsen M, et al. ((2010)) Induction of cardiac Angptl4 by dietary fatty acids is mediated by peroxisome proliferator-activated receptor beta/delta and protects against fatty acid-induced oxidative stress. Circ Res 106:: 1712--1721.
44. Alvarez-Guardia D, Palomer X, Coll T, Serrano L, Rodriguez-Calvo R, et al. ((2011)) PPARbeta/delta activation blocks lipid-induced inflammatory pathways in mouse heart and human cardiac cells. Biochim Biophys Acta 1811:: 59--67.
45. Karin M, Ben-Neriah Y, ((2000)) Phosphorylation meets ubiquitination: the control of NF-[kappa]B activity. Annu Rev Immunol 18:: 621--663.
46. Schwartz MW, Erickson JC, Baskin DG, Palmiter RD, ((1998)) Effect of fasting and leptin deficiency on hypothalamic neuropeptide Y gene transcription in vivo revealed by expression of a lacZ reporter gene. Endocrinology 139:: 2629--2635.
47. Andrews ZB, Liu ZW, Walllingford N, Erion DM, Borok E, et al. ((2008)) UCP2 mediates ghrelin's action on NPY/AgRP neurons by lowering free radicals. Nature 454:: 846--851.
48. Weinberg JM, ((2006)) Lipotoxicity. Kidney Int 70:: 1560--1566.
49. Coll T, Alvarez-Guardia D, Barroso E, Gomez-Foix AM, Palomer X, et al. ((2010)) Activation of peroxisome proliferator-activated receptor-{delta} by GW501516 prevents fatty acid-induced nuclear factor-{kappa}B activation and insulin resistance in skeletal muscle cells. Endocrinology 151:: 1560--1569.
50. Wu HT, Chen CT, Cheng KC, Li YX, Yeh CH, et al. ((2011)) Pharmacological activation of peroxisome proliferator-activated receptor delta improves insulin resistance and hepatic steatosis in high fat diet-induced diabetic mice. Horm Metab Res 43:: 631--635.
51. Frederich RC, Lollmann B, Hamann A, Napolitano-Rosen A, Kahn BB, et al. ((1995)) Expression of ob mRNA and its encoded protein in rodents. Impact of nutrition and obesity. J Clin Invest 96:: 1658--1663.
52. Sutton GM, Trevaskis JL, Hulver MW, McMillan RP, Markward NJ, et al. ((2006)) Diet-genotype interactions in the development of the obese, insulin-resistant phenotype of C57BL/6J mice lacking melanocortin-3 or-4 receptors. Endocrinology 147:: 2183--2196.
53. Shi Y, Hon M, Evans RM, ((2002)) The peroxisome proliferator-activated receptor delta, an integrator of transcriptional repression and nuclear receptor signaling. Proc Natl Acad Sci U S A 99:: 2613--2618.
54. Adhikary T, Kaddatz K, Finkernagel F, Schonbauer A, Meissner W, et al. ((2011)) Genomewide analyses define different modes of transcriptional regulation by peroxisome proliferator-activated receptor-beta/delta (PPARbeta/delta). PLoS One 6:: e16344.
55. Lee CH, Kang K, Mehl IR, Nofsinger R, Alaynick WA, et al. ((2006)) Peroxisome proliferator-activated receptor delta promotes very low-density lipoprotein-derived fatty acid catabolism in the macrophage. Proc Natl Acad Sci U S A 103:: 2434--2439.
56. Li Y, Cheng L, Qin Q, Liu J, Lo WK, et al. ((2009)) High-fat feeding in cardiomyocyte-restricted PPARdelta knockout mice leads to cardiac overexpression of lipid metabolic genes but fails to rescue cardiac phenotypes. J Mol Cell Cardiol 47:: 536--543.
57. Lee CH, Chawla A, Urbiztondo N, Liao D, Boisvert WA, et al. ((2003)) Transcriptional repression of atherogenic inflammation: modulation by PPARdelta. Science 302:: 453--457.
58. Arsenijevic D, de Bilbao F, Plamondon J, Paradis E, Vallet P, et al. ((2006)) Increased infarct size and lack of hyperphagic response after focal cerebral ischemia in peroxisome proliferator-activated receptor beta-deficient mice. J Cereb Blood Flow Metab 26:: 433--445.
59. Diano S, Liu ZW, Jeong JK, Dietrich MO, Ruan HB, et al. ((2011)) Peroxisome proliferation-associated control of reactive oxygen species sets melanocortin tone and feeding in diet-induced obesity. Nat Med.
60. Horvath TL, Diano S, Miyamoto S, Barry S, Gatti S, et al. ((2003)) Uncoupling proteins-2 and 3 influence obesity and inflammation in transgenic mice. Int J Obes Relat Metab Disord 27:: 433--442.
61. Bai Y, Onuma H, Bai X, Medvedev AV, Misukonis M, et al. ((2005)) Persistent nuclear factor-kappa B activation in Ucp2-/- mice leads to enhanced nitric oxide and inflammatory cytokine production. J Biol Chem 280:: 19062--19069.
62. Haines BA, Mehta SL, Pratt SM, Warden CH, Li PA, ((2010)) Deletion of mitochondrial uncoupling protein-2 increases ischemic brain damage after transient focal ischemia by altering gene expression patterns and enhancing inflammatory cytokines. J Cereb Blood Flow Metab 30:: 1825--1833.
63. Degasperi GR, Romanatto T, Denis RG, Araujo EP, Moraes JC, et al. ((2008)) UCP2 protects hypothalamic cells from TNF-alpha-induced damage. FEBS Lett 582:: 3103--3110.
64. Konig B, Rauer C, Rosenbaum S, Brandsch C, Eder K, et al. ((2009)) Fasting Upregulates PPARalpha Target Genes in Brain and Influences Pituitary Hormone Expression in a PPARalpha Dependent Manner. PPAR Res 2009:: 801609.
65. Gustafsson MC, Knight D, Palmer CN, ((2009)) Ligand modulated antagonism of PPARgamma by genomic and non-genomic actions of PPARdelta. PLoS One 4:: e7046.
66. Bugge A, Mandrup S, ((2010)) Molecular Mechanisms and Genome-Wide Aspects of PPAR Subtype Specific Transactivation. PPAR Res 2010.
67. Tronche F, Kellendonk C, Kretz O, Gass P, Anlag K, et al. ((1999)) Disruption of the glucocorticoid receptor gene in the nervous system results in reduced anxiety. Nat Genet 23:: 99--103.
68. Truett GE, Heeger P, Mynatt RL, Truett AA, Walker JA, et al. ((2000)) Preparation of PCR-quality mouse genomic DNA with hot sodium hydroxide and tris (HotSHOT). Biotechniques 29:: 52, 54.
69. Stanwood GD, Leitch DB, Savchenko V, Wu J, Fitsanakis VA, et al. ((2009)) Manganese exposure is cytotoxic and alters dopaminergic and GABAergic neurons within the basal ganglia. J Neurochem 110:: 378--389.
70. Sasaki T, Kim HJ, Kobayashi M, Kitamura YI, Yokota-Hashimoto H, et al. ((2010)) Induction of hypothalamic Sirt1 leads to cessation of feeding via agouti-related peptide. Endocrinology 151:: 2556--2566.
71. Boyle MP, Brewer JA, Funatsu M, Wozniak DF, Tsien JZ, et al. ((2005)) Acquired deficit of forebrain glucocorticoid receptor produces depression-like changes in adrenal axis regulation and behavior. Proc Natl Acad Sci U S A 102:: 473--478.
72. Saraswathi V, Hasty AH, ((2006)) The role of lipolysis in mediating the proinflammatory effects of very low density lipoproteins in mouse peritoneal macrophages. J Lipid Res 47:: 1406--1415.
73. Folch J, Lees M, Sloane Stanley GH, ((1957)) A simple method for the isolation and purification of total lipides from animal tissues. J Biol Chem 226:: 497--509.
74. Morrison WR, Smith LM, ((1964)) Preparation of Fatty Acid Methyl Esters and Dimethylacetals from Lipids with Boron Fluoride-Methanol. J Lipid Res 5:: 600--608.