Thromb Haemost 2017; 117(05): 981-991
DOI: 10.1160/TH16-12-0931
Blood Cells, Inflammation and Infection
Schattauer GmbH

Cold exposure down-regulates immune response pathways in ferret aortic perivascular adipose tissue

Bàrbara Reynés
1   Laboratory of Molecular Biology, Nutrition and Biotechnology, Universitat de les Illes Balears, Palma de Mallorca, Spain
2   CIBER de Fisiopatología de la Obesidad y Nutrición (CIBERobn), Palma de Mallorca, Spain
,
Evert M. van Schothorst
3   Human and Animal Physiology, Wageningen University, Wageningen, the Netherlands
,
Estefanía García-Ruiz
1   Laboratory of Molecular Biology, Nutrition and Biotechnology, Universitat de les Illes Balears, Palma de Mallorca, Spain
2   CIBER de Fisiopatología de la Obesidad y Nutrición (CIBERobn), Palma de Mallorca, Spain
,
Jaap Keijer
3   Human and Animal Physiology, Wageningen University, Wageningen, the Netherlands
,
Andreu Palou
1   Laboratory of Molecular Biology, Nutrition and Biotechnology, Universitat de les Illes Balears, Palma de Mallorca, Spain
2   CIBER de Fisiopatología de la Obesidad y Nutrición (CIBERobn), Palma de Mallorca, Spain
,
Paula Oliver
1   Laboratory of Molecular Biology, Nutrition and Biotechnology, Universitat de les Illes Balears, Palma de Mallorca, Spain
2   CIBER de Fisiopatología de la Obesidad y Nutrición (CIBERobn), Palma de Mallorca, Spain
› Institutsangaben
Financial support: CIBER de Fisiopatología de la Obesidad y Nutrición is an initiative of the ISCIII. This work was supported by the Spanish Government (Ministerio de Economía y Competitividad, INTERBIOBES-AGL2015–67019-P), by the EU FP7 project DIABAT (HEALTH-F2–2011–278373) and by the University of the Balearic Islands (BIOTHERM, FA42/2016). The Laboratory of Molecular Biology, Nutrition and Biotechnology is member of the European Research Network of Excellence NuGO (The European Nutrigenomics Organization, EU Contract: FOOD-CT-2004–506360 NUGO). E. García-Ruiz is recipient of a fellowship from the University of the Balearic Islands.
Weitere Informationen

Publikationsverlauf

Received: 15. Dezember 2017

Accepted after major revision: 27. Januar 2017

Publikationsdatum:
13. November 2017 (online)

Summary

Perivascular adipose tissue (PVAT) surrounds blood vessels and releases paracrine factors, such as cytokines, which regulate local inflammation. The inflammatory state of PVAT has an important role in vascular disease; a pro-inflammatory state has been related with atherosclerosis development, whereas an anti-inflammatory one is protective. Cold exposure beneficially affects immune responses and, could thus impact the pathogenesis of cardiovascular diseases. In this study, we investigated the effects of one-week of cold exposure at 4°C of ferrets on aortic PVAT (aPVAT) versus subcutaneous adipose tissue. Ferrets were used because of the similarity of their adipose tissues to those of humans. A ferret-specific Agilent microarray was designed to cover the complete ferret genome and global gene expression analysis was performed. The data showed that cold exposure altered gene expression mainly in aPVAT. Most of the regulated genes were associated with cell cycle, immune response and gene expression regulation, and were mainly down-regulated. Regarding the effects on immune response, cold acclimation decreased the expression of genes involved in antigen recognition and presentation, cytokine signalling and immune system maturation and activation. This immunosuppressive gene expression pattern was depot-specific, as it was not observed in the inguinal subcutaneous depot. Interestingly, this depression in immune response related genes was also evident in peripheral blood mononuclear cells (PBMC). In conclusion, these results reveal that cold acclimation produces an inhibition of immune response-related pathways in aPVAT, reflected in PBMC, indicative of an anti-inflammatory response, which can potentially be exploited for the enhancement or maintenance of cardiovascular health.

Supplementary Material to this article is available online at www.thrombosis-online.com.

 
  • References

  • 1 Szasz T, Bomfim GF, Webb RC. The influence of perivascular adipose tissue on vascular homeostasis. Vasc Health Risk Manag 2013; 09: 105-116.
  • 2 Cinti S. The adipose organ. Prostaglandins Leukot Essent Fatty Acids 2005; 73: 9-15.
  • 3 Chatterjee TK, Stoll LL, Denning GM. et al. Proinflammatory phenotype of perivascular adipocytes: influence of high-fat feeding. Circ Res 2009; 104: 541-549.
  • 4 Fitzgibbons TP, Kogan S, Aouadi M. et al. Similarity of mouse perivascular and brown adipose tissues and their resistance to diet-induced inflammation. Am J Physiol Heart Circ Physiol 2011; 301: H1425-1437.
  • 5 Gálvez-Prieto B, Bolbrinker J, Stucchi P. et al. Comparative expression analysis of the renin-angiotensin system components between white and brown perivascular adipose tissue. J Endocrinol 2008; 197: 55-64.
  • 6 Sacks H, Symonds ME. Anatomical locations of human brown adipose tissue: functional relevance and implications in obesity and type 2 diabetes. Diabetes 2013; 62: 1783-1790.
  • 7 Nedergaard J, Bengtsson T, Cannon B. Unexpected evidence for active brown adipose tissue in adult humans. Am J Physiol Endocrinol Metab 2007; 293: E444-452.
  • 8 Rajsheker S, Manka D, Blomkalns AL. et al. Crosstalk between perivascular adipose tissue and blood vessels. Curr Opin Pharmacol 2010; 10: 191-196.
  • 9 Henrichot E, Juge-Aubry CE, Pernin A. et al. Production of chemokines by perivascular adipose tissue: a role in the pathogenesis of atherosclerosis?. Arterioscler Thromb Vasc Biol 2005; 25: 2594-2599.
  • 10 Thalmann S, Meier CA. Local adipose tissue depots as cardiovascular risk factors. Cardiovasc Res 2007; 75: 690-701.
  • 11 Spiroglou SG, Kostopoulos CG, Varakis JN. et al. Adipokines in periaortic and epicardial adipose tissue: differential expression and relation to atherosclerosis. J Atheroscler Thromb 2010; 17: 115-130.
  • 12 Ouwens DM, Sell H, Greulich S. et al. The role of epicardial and perivascular adipose tissue in the pathophysiology of cardiovascular disease. J Cell Mol Med 2010; 14: 2223-2234.
  • 13 Fernández-Alfonso MS, Gil-Ortega M, Garca-Prieto CF. et al. Mechanisms of perivascular adipose tissue dysfunction in obesity. Int J Endocrinol 2013; 2013: 402053.
  • 14 Mazurek T, Zhang L, Zalewski A. et al. Human epicardial adipose tissue is a source of inflammatory mediators. Circulation 2003; 108: 2460-2466.
  • 15 Harrison DG, Guzik TJ, Lob HE. et al. Inflammation, immunity, and hypertension. Hypertension 2011; 57: 132-140.
  • 16 Van de Voorde J, Boydens C, Pauwels B. et al. Perivascular adipose tissue, inflammation and vascular dysfunction in obesity. Curr Vasc Pharmacol 2014; 12: 403-411.
  • 17 Himms-Hagen J. Brown adipose tissue thermogenesis: interdisciplinary studies. FASEB J 1990; 04: 2890-2898.
  • 18 Chang L, Villacorta L, Li R. et al. Loss of perivascular adipose tissue on peroxisome proliferator-activated receptor-? deletion in smooth muscle cells impairs intravascular thermoregulation and enhances atherosclerosis. Circulation 2012; 126: 1067-1078.
  • 19 Elenkov IJ, Wilder RL, Chrousos GP. et al. The sympathetic nerve--an integrative interface between two supersystems: the brain and the immune system. Pharmacol Rev 2000; 52: 595-638.
  • 20 Karp CL. Unstressing intemperate models: how cold stress undermines mouse modeling. J Exp Med 2012; 209: 1069-1074.
  • 21 Chatterjee TK, Aronow BJ, Tong WS. et al. Human coronary artery perivascular adipocytes overexpress genes responsible for regulating vascular morphology, inflammation, and hemostasis. Physiol Genomics 2013; 45: 697-709.
  • 22 Oliver P, Reynés B, Caimari A. et al. Peripheral blood mononuclear cells: a potential source of homeostatic imbalance markers associated with obesity development. Pflugers Arch 2013; 465: 459-468.
  • 23 Reynés B, Garca-Ruiz E, Palou A. et al. The intake of high-fat diets induces an obesogenic-like gene expression profile in peripheral blood mononuclear cells, which is reverted by dieting. Br J Nutr 2016; 1-9
  • 24 Reynés B, Garca-Ruiz E, Oliver P. et al. Gene expression of peripheral blood mononuclear cells is affected by cold exposure. Am J Physiol Regul Integr Comp Physiol. 2015 ajpregu.00221.2015
  • 25 Samara A, Marie B, Pfister M. et al. Leptin expression in Peripheral Blood Mononuclear Cells (PBMCs) is related with blood pressure variability. Clin Chim Acta 2008; 395: 47-50.
  • 26 Milagro FI, Miranda J, Portillo MP. et al. High-throughput sequencing of microRNAs in peripheral blood mononuclear cells: identification of potential weight loss biomarkers. PLoS One 2013; 08: e54319.
  • 27 Sclafani A, Gorman AN. Effects of age, sex, and prior body weight on the development of dietary obesity in adult rats. Physiol Behav 1977; 18: 1021-1026.
  • 28 Association AD. Executive summary: standards of medical care in diabetes--2011. Diabetes Care 2011; 34 (Suppl. 01) S4-10.
  • 29 Wolfgang MJ, Kurama T, Dai Y. et al. The brain-specific carnitine palmitoyltransferase-1c regulates energy homeostasis. Proc Natl Acad Sci USA 2006; 103: 7282-7287.
  • 30 Liew CC, Ma J, Tang HC. et al. The peripheral blood transcriptome dynamically reflects system wide biology: a potential diagnostic tool. J Lab Clin Med 2006; 147: 126-132.
  • 31 Murano I, Morroni M, Zingaretti MC. et al. Morphology of ferret subcutaneous adipose tissue after 6-month daily supplementation with oral beta-carotene. Biochim Biophys Acta 2005; 1740: 305-312.
  • 32 Hammer AS, Williams B, Dietz HH. et al. High-throughput immunophenotyping of 43 ferret lymphomas using tissue microarray technology. Vet Pathol 2007; 44: 196-203.
  • 33 Bruder CE, Yao S, Larson F. et al. Transcriptome sequencing and development of an expression microarray platform for the domestic ferret. BMC Genomics 2010; 11: 251.
  • 34 van Schothorst EM, Pagmantidis V, de Boer VC. et al. Assessment of reducing RNA input for Agilent oligo microarrays. Anal Biochem 2007; 363: 315-317.
  • 35 Hoek-van den Hil EF, Keijer J, Bunschoten A. et al. Quercetin induces hepatic lipid omega-oxidation and lowers serum lipid levels in mice. PLoS One 2013; 08: e51588.
  • 36 van Helden YG, Godschalk RW, Heil SG. et al. Downregulation of Fzd6 and Cthrc1 and upregulation of olfactory receptors and protocadherins by dietary beta-carotene in lungs of Bcmo1-/- mice. Carcinogenesis 2010; 31: 1329-1337.
  • 37 Pfaffl MW. A new mathematical model for relative quantification in real-time RT-PCR. Nucleic Acids Res 2001; 29: e45.
  • 38 Lang D, Knop J, Wesche H. et al. The type II IL-1 receptor interacts with the IL-1 receptor accessory protein: a novel mechanism of regulation of IL-1 responsiveness. J Immunol 1998; 161: 6871-6877.
  • 39 Palou M, Priego T, Sánchez J. et al. Gene expression patterns in visceral and subcutaneous adipose depots in rats are linked to their morphologic features. Cell Physiol Biochem 2009; 24: 547-556.
  • 40 Goundasheva D, Andonova M, Ivanov V. Changes in some parameters of the immune response in rats after cold stress. Zentralbl Veterinarmed B 1994; 41: 670-674.
  • 41 Jansk L, Pospsilová D, Honzová S. et al. Immune system of cold-exposed and cold-adapted humans. Eur J Appl Physiol Occup Physiol 1996; 72: 445-450.
  • 42 Fain JN, Sacks HS, Buehrer B. et al. Identification of omentin mRNA in human epicardial adipose tissue: comparison to omentin in subcutaneous, internal mammary artery periadventitial and visceral abdominal depots. Int J Obes 2008; 32: 810-815.
  • 43 Weisberg SP, McCann D, Desai M. et al. Obesity is associated with macrophage accumulation in adipose tissue. J Clin Invest 2003; 112: 1796-1808.
  • 44 Bussey CE, Withers SB, Aldous RG. et al. Obesity-Related Perivascular Adipose Tissue Damage Is Reversed by Sustained Weight Loss in the Rat. Arterioscler Thromb Vasc Biol 2016; 36: 1377-1385.
  • 45 Szasz T, Webb RC. Perivascular adipose tissue: more than just structural support. Clin Sci 2012; 122: 1-12.
  • 46 Kurki E, Shi J, Martonen E. et al. Distinct effects of calorie restriction on adipose tissue cytokine and angiogenesis profiles in obese and lean mice. Nutr Metab 2012; 09: 64.
  • 47 Police SB, Thatcher SE, Charnigo R. et al. Obesity promotes inflammation in periaortic adipose tissue and angiotensin II-induced abdominal aortic aneurysm formation. Arterioscler Thromb Vasc Biol 2009; 29: 1458-1464.
  • 48 Sonna LA, Fujita J, Gaffin SL. et al. Invited review: Effects of heat and cold stress on mammalian gene expression. J Appl Physiol 2002; 92: 1725-1742.
  • 49 Todorova VK, Beggs ML, Delongchamp RR. et al. Transcriptome profiling of peripheral blood cells identifies potential biomarkers for doxorubicin cardiotoxicity in a rat model. PLoS One 2012; 07: e48398.
  • 50 Chang DH, Rutledge JR, Patel AA. et al. The effect of lung cancer on cytokine expression in peripheral blood mononuclear cells. PLoS One 2013; 08: e64456.