Skip to main content

Advertisement

SpringerLink
Log in

Sexual dimorphism in obesity-related genes in the epicardial fat during aging

  • Original Article
  • Published:
Journal of Physiology and Biochemistry Aims and scope Submit manuscript

Abstract

Aging increases the risk of cardiovascular disease and metabolic syndrome. Alterations in epicardial fat play an important pathophysiological role in coronary artery disease and hypertension. We investigated the impact of normal aging on obesity-related genes in epicardial fat. Sex-specific changes in obesity-related genes with aging in epicardial fat (EF) were determined in young (6 months) and old (30/36 months) female and male, Fischer 344 × Brown Norway hybrid (FBN) rats, using a rat obesity RT2 PCR Array. Circulating sex hormone levels, body and heart weights were determined. Statistical significance was determined using two-tailed Student’s t test and Pearson’s correlation. Our results revealed sex-specific differences in obesity-related genes with aging. Dramatic changes in the expression profile of obesity-related genes in EF with aging in female, but not in male, FBN rats were observed. The older (30 months) female rats had more significant variations in the abundance of obesity-related genes in the EF compared to that seen in younger female rats or both age groups in male rats. A correlation of changes in obesity-related genes in EF to heart weights was observed in female rats, but not in male rats with aging. No correlation was observed to circulating sex hormone levels. Our findings indicate a dysfunctional EF in female rats with aging compared to male rats. These findings, with further functional validation, might help explain the sex differences in cardiovascular risk and mortality associated with aging observed in humans.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2

Similar content being viewed by others

References

  1. Aydin H, Toprak A, Deyneli O, Yazici D, Tarcin O, Sancak S, Yavuz D, Akalin S (2010) Epicardial fat tissue thickness correlates with endothelial dysfunction and other cardiovascular risk factors in patients with metabolic syndrome. Metab Syndr Relat Disord 8:229–234

    Article  CAS  PubMed  Google Scholar 

  2. Baker AR, Silva NF, Quinn DW, Harte AL, Pagano D, Bonser RS, Kumar S, McTernan PG (2006) Human epicardial adipose tissue expresses a pathogenic profile of adipocytokines in patients with cardiovascular disease. Cardiovasc Diabetol 5:1

    Article  PubMed  PubMed Central  Google Scholar 

  3. Begriche K, Girardet C, McDonald P, Butler AA (2013) Melanocortin-3 receptors and metabolic homeostasis. Prog Mol Biol Transl Sci 114:109–146

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. Cartwright MJ, Schlauch K, Lenburg ME, Tchkonia T, Pirtskhalava T, Cartwright A, Thomou T, Kirkland JL (2010) Aging, depot origin, and preadipocyte gene expression. J Gerontol A Biol Sci Med Sci 65:242–251

    Article  PubMed  Google Scholar 

  5. Chaowalit N, Lopez-Jimenez F (2008) Epicardial adipose tissue: friendly companion or hazardous neighbour for adjacent coronary arteries? Eur Heart J 29:695–697

    Article  PubMed  Google Scholar 

  6. Coutinho LL, Bergen WG, Romsos DR, Merkel RA (1993) Alpha-2 adrenergic receptor activity in porcine adipocytes is androgen and age/cell size dependent. Comp Biochem Physiol Comp Physiol 105:333–339

    Article  CAS  PubMed  Google Scholar 

  7. de Vos AM, Prokop M, Roos CJ, Meijs MF, van der Schouw YT, Rutten A, Gorter PM, Cramer MJ, Doevendans PA, Rensing BJ, Bartelink ML, Velthuis BK, Mosterd A, Bots ML (2008) Peri-coronary epicardial adipose tissue is related to cardiovascular risk factors and coronary artery calcification in post-menopausal women. Eur Heart J 29:777–783

    Article  PubMed  Google Scholar 

  8. El Khoudary SR, Shields KJ, Janssen I, Hanley C, Budoff MJ, Barinas-Mitchell E, Everson-Rose SA, Powell LH, Matthews KA (2015) Cardiovascular fat, menopause, and sex hormones in women: the SWAN cardiovascular fat ancillary study. J Clin Endocrinol Metab 100:3304–3312

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Fei J, Cook C, Blough E, Santanam N (2010) Age and sex mediated changes in epicardial fat adipokines. Atherosclerosis 212:488–494

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Fox CS, Liu Y, White CC, Feitosa M, Smith AV, Heard-Costa N, Lohman K, Johnson AD, Foster MC, Greenawalt DM, Griffin P, Ding J, Newman AB, Tylavsky F, Miljkovic I, Kritchevsky SB, Launer L, Garcia M, Eiriksdottir G, Carr JJ, Gudnason V, Harris TB, Cupples LA, Borecki IB (2012) Genome-wide association for abdominal subcutaneous and visceral adipose reveals a novel locus for visceral fat in women. PLoS Genet 8:e1002695

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Fox CS, Massaro JM, Hoffmann U, Pou KM, Maurovich-Horvat P, Liu CY, Vasan RS, Murabito JM, Meigs JB, Cupples LA, D'Agostino RB Sr, O'Donnell CJ (2007) Abdominal visceral and subcutaneous adipose tissue compartments: association with metabolic risk factors in the Framingham Heart Study. Circulation 116:39–48

    Article  PubMed  Google Scholar 

  12. Geer EB, Islam J, Buettner C (2014) Mechanisms of glucocorticoid-induced insulin resistance: focus on adipose tissue function and lipid metabolism. Endocrinol Metab Clin N Am 43:75–102

    Article  CAS  Google Scholar 

  13. Gettys TW, Rohlfs EM, Prpic V, Daniel KW, Taylor IL, Collins S (1995) Age-dependent changes in beta-adrenergic receptor subtypes and adenylyl cyclase activation in adipocytes from Fischer 344 rats. Endocrinology 136:2022–2032

    CAS  PubMed  Google Scholar 

  14. Guarente L, Kenyon C (2000) Genetic pathways that regulate ageing in model organisms. Nature 408:255–262

    Article  CAS  PubMed  Google Scholar 

  15. Guillermet-Guibert J, Lahlou H, Cordelier P, Bousquet C, Pyronnet S, Susini C (2005) Physiology of somatostatin receptors. J Endocrinol Investig 28:5–9

    CAS  Google Scholar 

  16. Hughes VA, Roubenoff R, Wood M, Frontera WR, Evans WJ, Fiatarone Singh MA (2004) Anthropometric assessment of 10-y changes in body composition in the elderly. Am J Clin Nutr 80:475–482

    CAS  PubMed  Google Scholar 

  17. Iacobellis G (2015) Local and systemic effects of the multifaceted epicardial adipose tissue depot. Nat Rev Endocrinol 11:363–371

    Article  CAS  PubMed  Google Scholar 

  18. Iacobellis G, Barbaro G (2008) The double role of epicardial adipose tissue as pro- and anti-inflammatory organ. Horm Metab Res 40:442–445

    Article  CAS  PubMed  Google Scholar 

  19. Kaddai V, Jager J, Gonzalez T, Najem-Lendom R, Bonnafous S, Tran A, Le Marchand-Brustel Y, Gual P, Tanti JF, Cormont M (2009) Involvement of TNF-alpha in abnormal adipocyte and muscle sortilin expression in obese mice and humans. Diabetologia 52:932–940

    Article  CAS  PubMed  Google Scholar 

  20. Kappeler L, De Magalhaes Filho C, Dupont J, Leneuve P, Cervera P, Perin L, Loudes C, Blaise A, Klein R, Epelbaum J, Le Bouc Y, Holzenberger M (2008) Brain IGF-1 receptors control mammalian growth and lifespan through a neuroendocrine mechanism. PLoS Biol 6:e254

    Article  PubMed  PubMed Central  Google Scholar 

  21. Karastergiou K, Fried SK (2013) Multiple adipose depots increase cardiovascular risk via local and systemic effects. Curr Atheroscler Rep 15:361

    Article  PubMed  PubMed Central  Google Scholar 

  22. Kobatake T, Watanabe Y, Matsuzawa Y, Tokunaga K, Fujioka S, Kawamoto T, Keno Y, Tarui S, Yoshida H (1991) Age-related changes in adrenergic alpha 1, alpha 2, and beta receptors of rat white fat cell membranes: an analysis using [3H]bunazosin as a novel ligand for the alpha 1 adrenoceptor. J Lipid Res 32:191–196

    CAS  PubMed  Google Scholar 

  23. Lago F, Dieguez C, Gomez-Reino J, Gualillo O (2007) Adipokines as emerging mediators of immune response and inflammation. Nat Clin Pract Rheumatol 3:716–724

    Article  CAS  PubMed  Google Scholar 

  24. Lunenfeld B (2008) An aging world—demographics and challenges. Gynecol Endocrinol 24:1–3

    Article  PubMed  Google Scholar 

  25. Michalakis K, Goulis DG, Vazaiou A, Mintziori G, Polymeris A, Abrahamian-Michalakis A (2013) Obesity in the ageing man. Metabolism 62:1341–1349

    Article  CAS  PubMed  Google Scholar 

  26. Ogden CL, Carroll MD, Kit BK, Flegal KM (2014) Prevalence of childhood and adult obesity in the United States, 2011-2012. JAMA 311:806–814

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Ogorodnikova AD, Khan UI, McGinn AP, Zeb I, Budoff MJ, Harman SM, Miller VM, Brinton EA, Manson JE, Hodis HN, Merriam GR, Cedars MI, Taylor HS, Naftolin F, Lobo RA, Santoro N, Wildman RP (2013) Ectopic fat and adipokines in metabolically benign overweight/obese women: the Kronos Early Estrogen Prevention Study. Obesity (Silver Spring) 21:1726–1733

    Article  CAS  Google Scholar 

  28. Perissinotto E, Pisent C, Sergi G, Grigoletto F (2002) Anthropometric measurements in the elderly: age and gender differences. Br J Nutr 87:177–186

    Article  CAS  PubMed  Google Scholar 

  29. Pezeshkian M, Mahtabipour MR (2013) Epicardial and subcutaneous adipose tissue fatty acids profiles in diabetic and non-diabetic patients candidate for coronary artery bypass graft. Bioimpacts 3:83–89

    PubMed  PubMed Central  Google Scholar 

  30. Pfaffl MW (2001) A new mathematical model for relative quantification in real-time RT-PCR. Nucleic Acids Res 29:e45

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  31. Qi L, Zhang C, van Dam RM, FB H (2007) Interleukin-6 genetic variability and adiposity: associations in two prospective cohorts and systematic review in 26,944 individuals. J Clin Endocrinol Metab 92:3618–3625

    Article  CAS  PubMed  Google Scholar 

  32. Rabkin SW (2007) Epicardial fat: properties, function and relationship to obesity. Obes Rev 8:253–261

    Article  CAS  PubMed  Google Scholar 

  33. Raggi P, Shaw LJ, Berman DS, Callister TQ (2004) Gender-based differences in the prognostic value of coronary calcification. J Women's Health (Larchmt) 13:273–283

    Article  Google Scholar 

  34. Sacks HS, Fain JN (2007) Human epicardial adipose tissue: a review. Am Heart J 153:907–917

    Article  CAS  PubMed  Google Scholar 

  35. Samara A, Herbeth B, Aubert R, Berrahmoune H, Fumeron F, Siest G, Visvikis-Siest S (2010) Sex-dependent associations of leptin with metabolic syndrome-related variables: the Stanislas study. Obesity (Silver Spring) 18:196–201

    Article  CAS  Google Scholar 

  36. Seboek D, Linscheid P, Zulewski H, Langer I, Christ-Crain M, Keller U, Muller B (2004) Somatostatin is expressed and secreted by human adipose tissue upon infection and inflammation. J Clin Endocrinol Metab 89:4833–4839

    Article  CAS  PubMed  Google Scholar 

  37. Shim IK, Cho KI, Kim HS, Heo JH, Cha TJ (2015) Impact of gender on the association of epicardial fat thickness, obesity, and circadian blood pressure pattern in hypertensive patients. J Diabetes Res 2015:924539

    Article  PubMed  PubMed Central  Google Scholar 

  38. Song do K, Hong YS, Lee H, Oh JY, Sung YA, Kim Y (2015) Increased epicardial adipose tissue thickness in type 2 diabetes mellitus and obesity. Diabetes Metab J 39:405–413

    Article  PubMed  PubMed Central  Google Scholar 

  39. St-Onge MP, Gallagher D (2010) Body composition changes with aging: the cause or the result of alterations in metabolic rate and macronutrient oxidation? Nutrition 26:152–155

    Article  CAS  PubMed  Google Scholar 

  40. Strandberg L, Mellstrom D, Ljunggren O, Grundberg E, Karlsson MK, Holmberg AH, Orwoll ES, Eriksson AL, Svedberg J, Bengtsson M, Ohlsson C, Jansson JO (2008) IL6 and IL1B polymorphisms are associated with fat mass in older men: the MrOS study Sweden. Obesity (Silver Spring) 16:710–713

    Article  CAS  Google Scholar 

  41. Tchkonia T, Morbeck DE, Von Zglinicki T, Van Deursen J, Lustgarten J, Scrable H, Khosla S, Jensen MD, Kirkland JL (2010) Fat tissue, aging, and cellular senescence. Aging Cell 9:667–684

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  42. Thompson NM, Gill DA, Davies R, Loveridge N, Houston PA, Robinson IC, Wells T (2004) Ghrelin and des-octanoyl ghrelin promote adipogenesis directly in vivo by a mechanism independent of the type 1a growth hormone secretagogue receptor. Endocrinology 145:234–242

    Article  CAS  PubMed  Google Scholar 

  43. Trevaskis JL, Gawronska-Kozak B, Sutton GM, McNeil M, Stephens JM, Smith SR, Butler AA (2007) Role of adiponectin and inflammation in insulin resistance of Mc3r and Mc4r knockout mice. Obesity (Silver Spring) 15:2664–2672

    Article  CAS  Google Scholar 

  44. Turturro A, Witt WW, Lewis S, Hass BS, Lipman RD, Hart RW (1999) Growth curves and survival characteristics of the animals used in the Biomarkers of Aging Program. J Gerontol A Biol Sci Med Sci 54:B492–B501

    Article  CAS  PubMed  Google Scholar 

  45. Ukkola O, Rankinen T, Lakka T, Leon AS, Skinner JS, Wilmore JH, Rao DC, Kesaniemi YA, Bouchard C (2005) Protein tyrosine phosphatase 1B variant associated with fat distribution and insulin metabolism. Obes Res 13:829–834

    Article  CAS  PubMed  Google Scholar 

  46. van Herpen NA, Schrauwen-Hinderling VB (2008) Lipid accumulation in non-adipose tissue and lipotoxicity. Physiol Behav 94:231–241

    Article  PubMed  Google Scholar 

  47. Wessells RJ, Fitzgerald E, Cypser JR, Tatar M, Bodmer R (2004) Insulin regulation of heart function in aging fruit flies. Nat Genet 36:1275–1281

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgements

The authors acknowledge Dr. Eric Blough for his generosity in sharing tissues from the FBN rats and Jia Fei for his technical help. The authors acknowledge the partial support of funds from National Institutes of Health, HL074239 (NS), 1R15AG051062-01 (NS), and 3P20RR016477-09S2. The funding sources had no direct involvement in any aspect of this manuscript.

Author information

Authors and Affiliations

  1. Department of Pharmacology, Physiology, & Toxicology, Joan C Edwards School of Medicine, Marshall University, One John Marshall Dr, Huntington, WV, 25755, USA

    Caitlin Kocher, Matthew Christiansen, Sarah Martin & Nalini Santanam

  2. Department of Medicine and Cardiology, Joan C Edwards School of Medicine, Marshall University, One John Marshall Dr, Huntington, WV, 25755, USA

    Christopher Adams, Paulette Wehner, Todd Gress & Nalini Santanam

Authors
  1. Caitlin Kocher
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Matthew Christiansen
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Sarah Martin
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Christopher Adams
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Paulette Wehner
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Todd Gress
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Nalini Santanam
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Nalini Santanam.

Ethics declarations

Marshall University’s Institutional Animal Care and Use Committee (IACUC) approved all protocols, and the animals were treated in compliance with Marshall University IACUC Committee regulations.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Kocher, C., Christiansen, M., Martin, S. et al. Sexual dimorphism in obesity-related genes in the epicardial fat during aging. J Physiol Biochem 73, 215–224 (2017). https://doi.org/10.1007/s13105-016-0542-0

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s13105-016-0542-0

Keywords

Search

Navigation