Skip to main content

Advertisement

SpringerLink
Log in

Obesity phenotypes: depot-differences in adipose tissue and their clinical implications

  • Review
  • Published:
Eating and Weight Disorders - Studies on Anorexia, Bulimia and Obesity Aims and scope Submit manuscript

Abstract

Obesity, defined as excess fat mass, increases risks for multiple chronic diseases, such as type 2 diabetes, cardiovascular disease, and several types of cancer. Beyond adiposity per se, the pattern of fat distribution, android or truncal as compared to gynoid or peripheral, has a profound influence on systemic metabolism and hence risk for obesity complications. Not only factors as genetics, environment, gender, and age account for the apparent compartmentalization of white adipose tissue (WAT) in the body. Indeed, the heterogeneity among different anatomical depots also appears to stem from their intrinsic diversity, including cellular developmental origin, proliferative capacity, glucose and lipid metabolism, insulin sensitivity, cytokine pattern, thermogenic ability, and vascularization. Under the obese condition, these depot-specific differences translate into specific WAT distribution patterns, giving rise to different cardiometabolic consequences. This review summarizes the clinical and mechanistic evidence for the depot-specific differences and the phenotypic characteristics of different WAT depots that link their depot-specific biology to obesity-specific complications.

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

Modified from [9]

Similar content being viewed by others

References

  1. Sacks FM, Bray GA, Carey VJ, Smith SR, Ryan DH, Anton SD, McManus K, Champagne CM, Bishop LM, Laranjo N, Leboff MS, Rood JC, de Jonge L, Greenway FL, Loria CM, Obarzanek E, Williamson DA (2009) Comparison of weight-loss diets with different compositions of fat, protein, and carbohydrates. N Engl J Med 360(9):859–873. https://doi.org/10.1056/NEJMoa0804748

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  2. Lombardo M, Bellia A, Padua E, Annino G, Guglielmi V, D’Adamo M, Iellamo F, Sbraccia P (2014) Morning meal more efficient for fat loss in a 3-month lifestyle intervention. J Am Coll Nutr 33(3):198–205. https://doi.org/10.1080/07315724.2013.863169

    Article  PubMed  Google Scholar 

  3. Bellia A, Salli M, Lombardo M, D’Adamo M, Guglielmi V, Tirabasso C, Giordani L, Federici M, Lauro D, Foti C, Sbraccia P (2014) Effects of whole body vibration plus diet on insulin-resistance in middle-aged obese subjects. Int J Sports Med 35(6):511–516. https://doi.org/10.1055/s-0033-1354358

    Article  CAS  PubMed  Google Scholar 

  4. Jakicic JM, Otto AD (2005) Physical activity considerations for the treatment and prevention of obesity. Am J Clin Nutr 82(1 Suppl):226S–229S

    Article  CAS  PubMed  Google Scholar 

  5. Lombardo M, Bellia A, Mattiuzzo F, Franchi A, Ferri C, Padua E, Guglielmi V, D’Adamo M, Annino G, Gentileschi P, Iellamo F, Lauro D, Federici M, Sbraccia P (2015) Frequent follow-up visits reduce weight regain in long-term management after bariatric surgery. Bariatric Surg Pract Patient Care 10(3):119–125. https://doi.org/10.1089/bari.2015.0021

    Article  Google Scholar 

  6. Frikke-Schmidt H, O’Rourke RW, Lumeng CN, Sandoval DA, Seeley RJ (2016) Does bariatric surgery improve adipose tissue function? Obes Rev 17(9):795–809. https://doi.org/10.1111/obr.12429

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Tilg H, Moschen AR (2006) Adipocytokines: mediators linking adipose tissue, inflammation and immunity. Nat Rev Immunol 6(10):772–783. https://doi.org/10.1038/nri1937

    Article  CAS  PubMed  Google Scholar 

  8. Guglielmi V, D’Adamo M, Bellia A, Ciotto RT, Federici M, Lauro D, Sbraccia P (2015) Iron status in obesity: an independent association with metabolic parameters and effect of weight loss. Nutr Metab Cardiovasc Dis 25(6):541–547. https://doi.org/10.1016/j.numecd.2015.02.012

    Article  CAS  PubMed  Google Scholar 

  9. Kwok KH, Lam KS, Xu A (2016) Heterogeneity of white adipose tissue: molecular basis and clinical implications. Exp Mol Med 48:e215. https://doi.org/10.1038/emm.2016.5

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Smith SR, Lovejoy JC, Greenway F, Ryan D, deJonge L, de la Bretonne J, Volafova J, Bray GA (2001) Contributions of total body fat, abdominal subcutaneous adipose tissue compartments, and visceral adipose tissue to the metabolic complications of obesity. Metabolism 50(4):425–435. https://doi.org/10.1053/meta.2001.21693

    Article  CAS  PubMed  Google Scholar 

  11. Geer EB, Shen W (2009) Gender differences in insulin resistance, body composition, and energy balance. Gend Med 6 Suppl 1:60–75. https://doi.org/10.1016/j.genm.2009.02.002

    Article  PubMed  Google Scholar 

  12. Ramirez ME, McMurry MP, Wiebke GA, Felten KJ, Ren K, Meikle AW, Iverius PH (1997) Evidence for sex steroid inhibition of lipoprotein lipase in men: comparison of abdominal and femoral adipose tissue. Metabolism 46(2):179–185

    Article  CAS  PubMed  Google Scholar 

  13. Pedersen SB, Kristensen K, Hermann PA, Katzenellenbogen JA, Richelsen B (2004) Estrogen controls lipolysis by up-regulating alpha2A-adrenergic receptors directly in human adipose tissue through the estrogen receptor alpha. Implications for the female fat distribution. J Clin Endocrinol Metab 89(4):1869–1878. https://doi.org/10.1210/jc.2003-031327

    Article  CAS  PubMed  Google Scholar 

  14. Singh R, Artaza JN, Taylor WE, Braga M, Yuan X, Gonzalez-Cadavid NF, Bhasin S (2006) Testosterone inhibits adipogenic differentiation in 3T3-L1 cells: nuclear translocation of androgen receptor complex with beta-catenin and T-cell factor 4 may bypass canonical Wnt signaling to down-regulate adipogenic transcription factors. Endocrinology 147(1):141–154. https://doi.org/10.1210/en.2004-1649

    Article  CAS  PubMed  Google Scholar 

  15. Lacasa D, Le Liepvre X, Ferre P, Dugail I (2001) Progesterone stimulates adipocyte determination and differentiation 1/sterol regulatory element-binding protein 1c gene expression. potential mechanism for the lipogenic effect of progesterone in adipose tissue. J Biol Chem 276(15):11512–11516. https://doi.org/10.1074/jbc.M008556200

    Article  CAS  PubMed  Google Scholar 

  16. Wajchenberg BL (2000) Subcutaneous and visceral adipose tissue: their relation to the metabolic syndrome. Endocr Rev 21(6):697–738. https://doi.org/10.1210/edrv.21.6.0415

    Article  CAS  PubMed  Google Scholar 

  17. White UA, Tchoukalova YD (2014) Sex dimorphism and depot differences in adipose tissue function. Biochim Biophys Acta 1842(3):377–392. https://doi.org/10.1016/j.bbadis.2013.05.006

    Article  CAS  PubMed  Google Scholar 

  18. Yang X, Schadt EE, Wang S, Wang H, Arnold AP, Ingram-Drake L, Drake TA, Lusis AJ (2006) Tissue-specific expression and regulation of sexually dimorphic genes in mice. Genome Res 16(8):995–1004. https://doi.org/10.1101/gr.5217506

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Lee MJ, Wu Y, Fried SK (2013) Adipose tissue heterogeneity: implication of depot differences in adipose tissue for obesity complications. Mol Aspects Med 34(1):1–11. https://doi.org/10.1016/j.mam.2012.10.001

    Article  CAS  PubMed  Google Scholar 

  20. Anand SS, Tarnopolsky MA, Rashid S, Schulze KM, Desai D, Mente A, Rao S, Yusuf S, Gerstein HC, Sharma AM (2011) Adipocyte hypertrophy, fatty liver and metabolic risk factors in South Asians: the Molecular Study of Health and Risk in Ethnic Groups (mol-SHARE). PLoS One 6(7):e22112. https://doi.org/10.1371/journal.pone.0022112

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Guglielmi V, Maresca L, D’Adamo M, Di Roma M, Lanzillo C, Federici M, Lauro D, Preziosi P, Bellia A, Sbraccia P (2014) Age-related different relationships between ectopic adipose tissues and measures of central obesity in sedentary subjects. PLoS One 9(7):e103381. https://doi.org/10.1371/journal.pone.0103381

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. Lundgren M, Svensson M, Lindmark S, Renstrom F, Ruge T, Eriksson JW (2007) Fat cell enlargement is an independent marker of insulin resistance and ‘hyperleptinaemia’. Diabetologia 50(3):625–633. https://doi.org/10.1007/s00125-006-0572-1

    Article  CAS  PubMed  Google Scholar 

  23. Tchkonia T, Tchoukalova YD, Giorgadze N, Pirtskhalava T, Karagiannides I, Forse RA, Koo A, Stevenson M, Chinnappan D, Cartwright A, Jensen MD, Kirkland JL (2005) Abundance of two human preadipocyte subtypes with distinct capacities for replication, adipogenesis, and apoptosis varies among fat depots. Am J Physiol Endocrinol Metab 288(1):E267–E277. https://doi.org/10.1152/ajpendo.00265.2004

    Article  CAS  PubMed  Google Scholar 

  24. Tchkonia T, Giorgadze N, Pirtskhalava T, Thomou T, DePonte M, Koo A, Forse RA, Chinnappan D, Martin-Ruiz C, von Zglinicki T, Kirkland JL (2006) Fat depot-specific characteristics are retained in strains derived from single human preadipocytes. Diabetes 55(9):2571–2578. https://doi.org/10.2337/db06-0540

    Article  CAS  PubMed  Google Scholar 

  25. Gesta S, Bluher M, Yamamoto Y, Norris AW, Berndt J, Kralisch S, Boucher J, Lewis C, Kahn CR (2006) Evidence for a role of developmental genes in the origin of obesity and body fat distribution. Proc Natl Acad Sci USA 103(17):6676–6681. https://doi.org/10.1073/pnas.0601752103

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. Guglielmi V, D’Adamo M, Menghini R, Cardellini M, Gentileschi P, Federici M, Sbraccia P (2017) MicroRNA 21 is up-regulated in adipose tissue of obese diabetic subjects. Nutr Healthy Aging 4:141–145. https://doi.org/10.3233/NHA-160020

    Article  PubMed  PubMed Central  Google Scholar 

  27. Gilad S, Meiri E, Yogev Y, Benjamin S, Lebanony D, Yerushalmi N, Benjamin H, Kushnir M, Cholakh H, Melamed N, Bentwich Z, Hod M, Goren Y, Chajut A (2008) Serum microRNAs are promising novel biomarkers. PLoS One 3(9):e3148. https://doi.org/10.1371/journal.pone.0003148

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Joe AW, Yi L, Even Y, Vogl AW, Rossi FM (2009) Depot-specific differences in adipogenic progenitor abundance and proliferative response to high-fat diet. Stem Cells 27(10):2563–2570. https://doi.org/10.1002/stem.190

    Article  CAS  PubMed  Google Scholar 

  29. Spalding KL, Arner E, Westermark PO, Bernard S, Buchholz BA, Bergmann O, Blomqvist L, Hoffstedt J, Naslund E, Britton T, Concha H, Hassan M, Ryden M, Frisen J, Arner P (2008) Dynamics of fat cell turnover in humans. Nature 453(7196):783–787. https://doi.org/10.1038/nature06902

    Article  CAS  PubMed  Google Scholar 

  30. Skurk T, Alberti-Huber C, Herder C, Hauner H (2007) Relationship between adipocyte size and adipokine expression and secretion. J Clin Endocrinol Metab 92 (3):1023–1033. https://doi.org/10.1210/jc.2006-1055

    Article  CAS  PubMed  Google Scholar 

  31. Giordano A, Murano I, Mondini E, Perugini J, Smorlesi A, Severi I, Barazzoni R, Scherer PE, Cinti S (2013) Obese adipocytes show ultrastructural features of stressed cells and die of pyroptosis. J Lipid Res 54(9):2423–2436. https://doi.org/10.1194/jlr.M038638

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  32. Strissel KJ, Stancheva Z, Miyoshi H, Perfield JW, 2nd, DeFuria J, Jick Z, Greenberg AS, Obin MS (2007) Adipocyte death, adipose tissue remodeling, and obesity complications. Diabetes 56 (12):2910–2918. https://doi.org/10.2337/db07-0767

    Article  CAS  PubMed  Google Scholar 

  33. Pellegrinelli V, Carobbio S, Vidal-Puig A (2016) Adipose tissue plasticity: how fat depots respond differently to pathophysiological cues. Diabetologia 59(6):1075–1088. https://doi.org/10.1007/s00125-016-3933-4

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  34. Kim SM, Lun M, Wang M, Senyo SE, Guillermier C, Patwari P, Steinhauser ML (2014) Loss of white adipose hyperplastic potential is associated with enhanced susceptibility to insulin resistance. Cell Metab 20(6):1049–1058. https://doi.org/10.1016/j.cmet.2014.10.010

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  35. Cinti S (2017) UCP1 protein: the molecular hub of adipose organ plasticity. Biochimie 134:71–76. https://doi.org/10.1016/j.biochi.2016.09.008

    Article  CAS  PubMed  Google Scholar 

  36. Vijgen GH, Bouvy ND, Teule GJ, Brans B, Schrauwen P, van Marken Lichtenbelt WD (2011) Brown adipose tissue in morbidly obese subjects. PLoS One 6(2):e17247. https://doi.org/10.1371/journal.pone.0017247

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  37. Virtanen KA, Lidell ME, Orava J, Heglind M, Westergren R, Niemi T, Taittonen M, Laine J, Savisto NJ, Enerback S, Nuutila P (2009) Functional brown adipose tissue in healthy adults. N Engl J Med 360(15):1518–1525. https://doi.org/10.1056/NEJMoa0808949

    Article  CAS  PubMed  Google Scholar 

  38. Cypess AM, Lehman S, Williams G, Tal I, Rodman D, Goldfine AB, Kuo FC, Palmer EL, Tseng YH, Doria A, Kolodny GM, Kahn CR (2009) Identification and importance of brown adipose tissue in adult humans. N Engl J Med 360(15):1509–1517. https://doi.org/10.1056/NEJMoa0810780

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  39. Vitali A, Murano I, Zingaretti MC, Frontini A, Ricquier D, Cinti S (2012) The adipose organ of obesity-prone C57BL/6J mice is composed of mixed white and brown adipocytes. J Lipid Res 53(4):619–629. https://doi.org/10.1194/jlr.M018846

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  40. Cousin B, Cinti S, Morroni M, Raimbault S, Ricquier D, Penicaud L, Casteilla L (1992) Occurrence of brown adipocytes in rat white adipose tissue: molecular and morphological characterization. J Cell Sci 103(Pt 4):931–942

    CAS  PubMed  Google Scholar 

  41. De Matteis R, Lucertini F, Guescini M, Polidori E, Zeppa S, Stocchi V, Cinti S, Cuppini R (2013) Exercise as a new physiological stimulus for brown adipose tissue activity. Nutr Metab Cardiovasc Dis 23(6):582–590. https://doi.org/10.1016/j.numecd.2012.01.013

    Article  CAS  PubMed  Google Scholar 

  42. Wang QA, Tao C, Gupta RK, Scherer PE (2013) Tracking adipogenesis during white adipose tissue development, expansion and regeneration. Nat Med 19(10):1338–1344. https://doi.org/10.1038/nm.3324

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  43. Giordano A, Frontini A, Cinti S (2016) Convertible visceral fat as a therapeutic target to curb obesity. Nat Rev Drug Discov 15(6):405–424. https://doi.org/10.1038/nrd.2016.31

    Article  CAS  PubMed  Google Scholar 

  44. Seale P, Bjork B, Yang W, Kajimura S, Chin S, Kuang S, Scime A, Devarakonda S, Conroe HM, Erdjument-Bromage H, Tempst P, Rudnicki MA, Beier DR, Spiegelman BM (2008) PRDM16 controls a brown fat/skeletal muscle switch. Nature 454(7207):961–967. https://doi.org/10.1038/nature07182

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  45. Frontini A, Vitali A, Perugini J, Murano I, Romiti C, Ricquier D, Guerrieri M, Cinti S (2013) White-to-brown transdifferentiation of omental adipocytes in patients affected by pheochromocytoma. Biochim Biophys Acta 1831(5):950–959. https://doi.org/10.1016/j.bbalip.2013.02.005

    Article  CAS  PubMed  Google Scholar 

  46. Cheng W, Zhu Z, Jin X, Chen L, Zhuang H, Li F (2012) Intense FDG activity in the brown adipose tissue in omental and mesenteric regions in a patient with malignant pheochromocytoma. Clin Nucl Med 37(5):514–515. https://doi.org/10.1097/RLU.0b013e31824d2121

    Article  PubMed  Google Scholar 

  47. Dong A, Wang Y, Lu J, Zuo C (2014) Hypermetabolic mesenteric brown adipose tissue on dual-time point FDG PET/CT in a patient with benign retroperitoneal pheochromocytoma. Clin Nucl Med 39(3):e229–e232. https://doi.org/10.1097/RLU.0b013e3182816515

    Article  PubMed  Google Scholar 

  48. Arner P, Lithell H, Wahrenberg H, Bronnegard M (1991) Expression of lipoprotein lipase in different human subcutaneous adipose tissue regions. J Lipid Res 32(3):423–429

    CAS  PubMed  Google Scholar 

  49. Karpe F, Pinnick KE (2015) Biology of upper-body and lower-body adipose tissue—link to whole-body phenotypes. Nat Rev Endocrinol 11(2):90–100. https://doi.org/10.1038/nrendo.2014.185

    Article  CAS  PubMed  Google Scholar 

  50. Veilleux A, Blouin K, Rheaume C, Daris M, Marette A, Tchernof A (2009) Glucose transporter 4 and insulin receptor substrate-1 messenger RNA expression in omental and subcutaneous adipose tissue in women. Metabolism 58(5):624–631. https://doi.org/10.1016/j.metabol.2008.12.007

    Article  CAS  PubMed  Google Scholar 

  51. Virtanen KA, Lonnroth P, Parkkola R, Peltoniemi P, Asola M, Viljanen T, Tolvanen T, Knuuti J, Ronnemaa T, Huupponen R, Nuutila P (2002) Glucose uptake and perfusion in subcutaneous and visceral adipose tissue during insulin stimulation in nonobese and obese humans. J Clin Endocrinol Metab 87(8):3902–3910. https://doi.org/10.1210/jcem.87.8.8761

    Article  CAS  PubMed  Google Scholar 

  52. Arner P (1999) Catecholamine-induced lipolysis in obesity. Int J Obes Relat Metab Disord 23(Suppl 1):10–13

    Article  PubMed  Google Scholar 

  53. Van Harmelen V, Lonnqvist F, Thorne A, Wennlund A, Large V, Reynisdottir S, Arner P (1997) Noradrenaline-induced lipolysis in isolated mesenteric, omental and subcutaneous adipocytes from obese subjects. Int J Obes Relat Metab Disord 21(11):972–979

    Article  PubMed  Google Scholar 

  54. Nielsen S, Guo Z, Johnson CM, Hensrud DD, Jensen MD (2004) Splanchnic lipolysis in human obesity. J Clin Invest 113(11):1582–1588. https://doi.org/10.1172/JCI21047

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  55. Dolinkova M, Dostalova I, Lacinova Z, Michalsky D, Haluzikova D, Mraz M, Kasalicky M, Haluzik M (2008) The endocrine profile of subcutaneous and visceral adipose tissue of obese patients. Mol Cell Endocrinol 291(1–2):63–70. https://doi.org/10.1016/j.mce.2008.05.001

    Article  CAS  PubMed  Google Scholar 

  56. Alvehus M, Buren J, Sjostrom M, Goedecke J, Olsson T (2010) The human visceral fat depot has a unique inflammatory profile. Obesity (Silver Spring) 18(5):879–883. https://doi.org/10.1038/oby.2010.22

    Article  CAS  Google Scholar 

  57. Donath MY, Shoelson SE (2011) Type 2 diabetes as an inflammatory disease. Nat Rev Immunol 11(2):98–107. https://doi.org/10.1038/nri2925

    Article  CAS  PubMed  Google Scholar 

  58. Altintas MM, Azad A, Nayer B, Contreras G, Zaias J, Faul C, Reiser J, Nayer A (2011) Mast cells, macrophages, and crown-like structures distinguish subcutaneous from visceral fat in mice. J Lipid Res 52(3):480–488. https://doi.org/10.1194/jlr.M011338

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  59. Guglielmi V, Cardellini M, Cinti F, Corgosinho F, Cardolini I, D’Adamo M, Zingaretti MC, Bellia A, Lauro D, Gentileschi P, Federici M, Cinti S, Sbraccia P (2015) Omental adipose tissue fibrosis and insulin resistance in severe obesity. Nutr Diabetes 5:e175. https://doi.org/10.1038/nutd.2015.22

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  60. Wernstedt Asterholm I, Tao C, Morley TS, Wang QA, Delgado-Lopez F, Wang ZV, Scherer PE (2014) Adipocyte inflammation is essential for healthy adipose tissue expansion and remodeling. Cell Metab 20(1):103–118. https://doi.org/10.1016/j.cmet.2014.05.005

    Article  CAS  PubMed  Google Scholar 

  61. Khan T, Muise ES, Iyengar P, Wang ZV, Chandalia M, Abate N, Zhang BB, Bonaldo P, Chua S, Scherer PE (2009) Metabolic dysregulation and adipose tissue fibrosis: role of collagen VI. Mol Cell Biol 29(6):1575–1591. https://doi.org/10.1128/MCB.01300-08

    Article  CAS  PubMed  Google Scholar 

  62. Michaud A, Tordjman J, Pelletier M, Liu Y, Laforest S, Noel S, Le Naour G, Bouchard C, Clement K, Tchernof A (2016) Relevance of omental pericellular adipose tissue collagen in the pathophysiology of human abdominal obesity and related cardiometabolic risk. Int J Obes (Lond) 40(12):1823–1831. https://doi.org/10.1038/ijo.2016.173

    Article  CAS  Google Scholar 

  63. Pasarica M, Sereda OR, Redman LM, Albarado DC, Hymel DT, Roan LE, Rood JC, Burk DH, Smith SR (2009) Reduced adipose tissue oxygenation in human obesity: evidence for rarefaction, macrophage chemotaxis, and inflammation without an angiogenic response. Diabetes 58(3):718–725. https://doi.org/10.2337/db08-1098

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  64. Gealekman O, Guseva N, Hartigan C, Apotheker S, Gorgoglione M, Gurav K, Tran KV, Straubhaar J, Nicoloro S, Czech MP, Thompson M, Perugini RA, Corvera S (2011) Depot-specific differences and insufficient subcutaneous adipose tissue angiogenesis in human obesity. Circulation 123(2):186–194. https://doi.org/10.1161/CIRCULATIONAHA.110.970145

    Article  PubMed  PubMed Central  Google Scholar 

  65. Goossens GH, Blaak EE (2015) Adipose tissue dysfunction and impaired metabolic health in human obesity: a matter of oxygen? Front Endocrinol (Lausanne) 6:55. https://doi.org/10.3389/fendo.2015.00055

    Article  Google Scholar 

  66. St-Pierre J, Lemieux I, Perron P, Brisson D, Santure M, Vohl MC, Despres JP, Gaudet D (2007) Relation of the “hypertriglyceridemic waist” phenotype to earlier manifestations of coronary artery disease in patients with glucose intolerance and type 2 diabetes mellitus. Am J Cardiol 99(3):369–373. https://doi.org/10.1016/j.amjcard.2006.08.041

    Article  CAS  PubMed  Google Scholar 

  67. Coutinho T, Goel K, Correa de Sa D, Kragelund C, Kanaya AM, Zeller M, Park JS, Kober L, Torp-Pedersen C, Cottin Y, Lorgis L, Lee SH, Kim YJ, Thomas R, Roger VL, Somers VK, Lopez-Jimenez F (2011) Central obesity and survival in subjects with coronary artery disease: a systematic review of the literature and collaborative analysis with individual subject data. J Am Coll Cardiol 57(19):1877–1886. https://doi.org/10.1016/j.jacc.2010.11.058

    Article  PubMed  Google Scholar 

  68. Bray GA, Jablonski KA, Fujimoto WY, Barrett-Connor E, Haffner S, Hanson RL, Hill JO, Hubbard V, Kriska A, Stamm E, Pi-Sunyer FX (2008) Relation of central adiposity and body mass index to the development of diabetes in the Diabetes Prevention Program. Am J Clin Nutr 87(5):1212–1218

    Article  CAS  PubMed  Google Scholar 

  69. Fabbrini E, Magkos F, Mohammed BS, Pietka T, Abumrad NA, Patterson BW, Okunade A, Klein S (2009) Intrahepatic fat, not visceral fat, is linked with metabolic complications of obesity. Proc Natl Acad Sci USA 106(36):15430–15435. https://doi.org/10.1073/pnas.0904944106

    Article  PubMed  PubMed Central  Google Scholar 

  70. Karastergiou K, Fried SK (2013) Multiple adipose depots increase cardiovascular risk via local and systemic effects. Curr Atheroscler Rep 15(10):361. https://doi.org/10.1007/s11883-013-0361-5

    Article  PubMed  PubMed Central  Google Scholar 

  71. Pramyothin P, Karastergiou K (2016) What can we learn from interventions that change fat distribution? Curr Obes Rep 5(2):271–281. https://doi.org/10.1007/s13679-016-0215-x

    Article  PubMed  Google Scholar 

  72. Hernandez TL, Bessesen DH, Cox-York KA, Erickson CB, Law CK, Anderson MK, Wang H, Jackman MR, Van Pelt RE (2015) Femoral lipectomy increases postprandial lipemia in women. Am J Physiol Endocrinol Metab 309(1):E63–E71. https://doi.org/10.1152/ajpendo.00080.2015

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  73. Cameron AJ, Magliano DJ, Soderberg S (2013) A systematic review of the impact of including both waist and hip circumference in risk models for cardiovascular diseases, diabetes and mortality. Obes Rev 14(1):86–94. https://doi.org/10.1111/j.1467-789X.2012.01051.x

    Article  CAS  PubMed  Google Scholar 

  74. Lombardi F, Gullotta F, Columbaro M, Filareto A, D’Adamo M, Vielle A, Guglielmi V, Nardone AM, Azzolini V, Grosso E, Lattanzi G, D’Apice MR, Masala S, Maraldi NM, Sbraccia P, Novelli G (2007) Compound heterozygosity for mutations in LMNA in a patient with a myopathic and lipodystrophic mandibuloacral dysplasia type A phenotype. J Clin Endocrinol Metab 92(11):4467–4471. https://doi.org/10.1210/jc.2007-0116

    Article  CAS  PubMed  Google Scholar 

  75. Guglielmi V, D’Adamo M, D’Apice MR, Bellia A, Lauro D, Federici M, Lauro R, Novelli G, Sbraccia P (2010) Elbow deformities in a patient with mandibuloacral dysplasia type A. Am J Med Genet A 152A(11):2711–2713. https://doi.org/10.1002/ajmg.a.33700

    Article  PubMed  Google Scholar 

  76. McLaughlin TM, Liu T, Yee G, Abbasi F, Lamendola C, Reaven GM, Tsao P, Cushman SW, Sherman A (2010) Pioglitazone increases the proportion of small cells in human abdominal subcutaneous adipose tissue. Obesity (Silver Spring) 18(5):926–931. https://doi.org/10.1038/oby.2009.380

    Article  CAS  Google Scholar 

  77. Bosello O, Donataccio MP, Cuzzolaro M (2016) Obesity or obesities? Controversies on the association between body mass index and premature mortality. Eat Weight Disord 21(2):165–174. https://doi.org/10.1007/s40519-016-0278-4

    Article  PubMed  Google Scholar 

  78. Bellia A, Marinoni G, D’Adamo M, Guglielmi V, Lombardo M, Donadel G, Gentileschi P, Lauro D, Federici M, Lauro R, Sbraccia P (2012) Parathyroid hormone and insulin resistance in distinct phenotypes of severe obesity: a cross-sectional analysis in middle-aged men and premenopausal women. J Clin Endocrinol Metab 97(12):4724–4732. https://doi.org/10.1210/jc.2012-2513

    Article  CAS  PubMed  Google Scholar 

  79. Bluher M (2014) Are metabolically healthy obese individuals really healthy? Eur J Endocrinol 171(6):R209–R219. https://doi.org/10.1530/EJE-14-0540

    Article  CAS  PubMed  Google Scholar 

  80. Marques-Vidal P, Pecoud A, Hayoz D, Paccaud F, Mooser V, Waeber G, Vollenweider P (2010) Normal weight obesity: relationship with lipids, glycaemic status, liver enzymes and inflammation. Nutr Metab Cardiovasc Dis 20(9):669–675. https://doi.org/10.1016/j.numecd.2009.06.001

    Article  CAS  PubMed  Google Scholar 

  81. Badoud F, Perreault M, Zulyniak MA, Mutch DM (2015) Molecular insights into the role of white adipose tissue in metabolically unhealthy normal weight and metabolically healthy obese individuals. FASEB J 29(3):748–758. https://doi.org/10.1096/fj.14-263913

    Article  CAS  PubMed  Google Scholar 

  82. Srdic B, Stokic E, Korac A, Ukropina M, Velickovic K, Breberina M (2010) Morphological characteristics of abdominal adipose tissue in normal-weight and obese women of different metabolic profiles. Exp Clin Endocrinol Diabetes 118(10):713–718. https://doi.org/10.1055/s-0030-1254165

    Article  CAS  PubMed  Google Scholar 

  83. Kloting N, Fasshauer M, Dietrich A, Kovacs P, Schon MR, Kern M, Stumvoll M, Bluher M (2010) Insulin-sensitive obesity. Am J Physiol Endocrinol Metab 299(3):E506–E515. https://doi.org/10.1152/ajpendo.00586.2009

    Article  CAS  PubMed  Google Scholar 

  84. Item F, Konrad D (2012) Visceral fat and metabolic inflammation: the portal theory revisited. Obes Rev 13 Suppl 2:30–39. https://doi.org/10.1111/j.1467-789X.2012.01035.x

    Article  CAS  PubMed  Google Scholar 

  85. Carobbio S, Rodriguez-Cuenca S, Vidal-Puig A (2011) Origins of metabolic complications in obesity: ectopic fat accumulation. The importance of the qualitative aspect of lipotoxicity. Curr Opin Clin Nutr Metab Care 14(6):520–526. https://doi.org/10.1097/MCO.0b013e32834ad966

    Article  CAS  PubMed  Google Scholar 

  86. Bachman ES, Dhillon H, Zhang CY, Cinti S, Bianco AC, Kobilka BK, Lowell BB (2002) BetaAR signaling required for diet-induced thermogenesis and obesity resistance. Science 297(5582):843–845. https://doi.org/10.1126/science.1073160

    Article  CAS  PubMed  Google Scholar 

  87. Feldmann HM, Golozoubova V, Cannon B, Nedergaard J (2009) UCP1 ablation induces obesity and abolishes diet-induced thermogenesis in mice exempt from thermal stress by living at thermoneutrality. Cell Metab 9(2):203–209. https://doi.org/10.1016/j.cmet.2008.12.014

    Article  CAS  PubMed  Google Scholar 

  88. Saito M, Okamatsu-Ogura Y, Matsushita M, Watanabe K, Yoneshiro T, Nio-Kobayashi J, Iwanaga T, Miyagawa M, Kameya T, Nakada K, Kawai Y, Tsujisaki M (2009) High incidence of metabolically active brown adipose tissue in healthy adult humans: effects of cold exposure and adiposity. Diabetes 58(7):1526–1531. https://doi.org/10.2337/db09-0530

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  89. Guglielmi V, Sbraccia P (2017) Type 2 diabetes: does pancreatic fat really matter? Diabetes Metab Res Rev. https://doi.org/10.1002/dmrr.2955

    Article  PubMed  Google Scholar 

  90. Sacks HS, Fain JN (2007) Human epicardial adipose tissue: a review. Am Heart J 153(6):907–917. https://doi.org/10.1016/j.ahj.2007.03.019

    Article  CAS  PubMed  Google Scholar 

  91. Fain JN, Sacks HS, Bahouth SW, Tichansky DS, Madan AK, Cheema PS (2010) Human epicardial adipokine messenger RNAs: comparisons of their expression in substernal, subcutaneous, and omental fat. Metabolism 59(9):1379–1386. https://doi.org/10.1016/j.metabol.2009.12.027

    Article  CAS  PubMed  Google Scholar 

  92. Sacks HS, Fain JN, Holman B, Cheema P, Chary A, Parks F, Karas J, Optican R, Bahouth SW, Garrett E, Wolf RY, Carter RA, Robbins T, Wolford D, Samaha J (2009) Uncoupling protein-1 and related messenger ribonucleic acids in human epicardial and other adipose tissues: epicardial fat functioning as brown fat. J Clin Endocrinol Metab 94(9):3611–3615. https://doi.org/10.1210/jc.2009-0571

    Article  CAS  PubMed  Google Scholar 

  93. Mazurek T, Zhang L, Zalewski A, Mannion JD, Diehl JT, Arafat H, Sarov-Blat L, O’Brien S, Keiper EA, Johnson AG, Martin J, Goldstein BJ, Shi Y (2003) Human epicardial adipose tissue is a source of inflammatory mediators. Circulation 108(20):2460–2466. https://doi.org/10.1161/01.CIR.0000099542.57313.C5

    Article  PubMed  Google Scholar 

  94. Iacobellis G, Cotesta D, Petramala L, De Santis V, Vitale D, Tritapepe L, Letizia C (2010) Intracoronary adiponectin levels rapidly and significantly increase after coronary revascularization. Int J Cardiol 144(1):160–163. https://doi.org/10.1016/j.ijcard.2008.12.155

    Article  PubMed  Google Scholar 

  95. Iacobellis G, Leonetti F, Singh N, A MS (2007) Relationship of epicardial adipose tissue with atrial dimensions and diastolic function in morbidly obese subjects. Int J Cardiol 115(2):272–273. https://doi.org/10.1016/j.ijcard.2006.04.016

    Article  PubMed  Google Scholar 

  96. Guglielmi V, Maresca L, Lanzillo C, Marinoni GM, D’Adamo M, Di Roma M, Preziosi P, Bellia A, Calo L, Sbraccia P (2016) Relationship between regional fat distribution and hypertrophic cardiomyopathy phenotype. PLoS One 11(7):e0158892. https://doi.org/10.1371/journal.pone.0158892

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  97. Nagashima K, Okumura Y, Watanabe I, Nakai T, Ohkubo K, Kofune T, Kofune M, Mano H, Sonoda K, Hirayama A (2011) Association between epicardial adipose tissue volumes on 3-dimensional reconstructed CT images and recurrence of atrial fibrillation after catheter ablation. Circ J 75(11):2559–2565

    Article  CAS  PubMed  Google Scholar 

  98. Venteclef N, Guglielmi V, Balse E, Gaborit B, Cotillard A, Atassi F, Amour J, Leprince P, Dutour A, Clement K, Hatem SN (2015) Human epicardial adipose tissue induces fibrosis of the atrial myocardium through the secretion of adipo-fibrokines. Eur Heart J 36(13):795–805. https://doi.org/10.1093/eurheartj/eht099

    Article  CAS  PubMed  Google Scholar 

  99. Guglielmi V, Sbraccia P (2017) Epicardial adipose tissue: at the heart of the obesity complications. Acta Diabetol. https://doi.org/10.1007/s00592-017-1020-z

    Article  PubMed  Google Scholar 

  100. Galvez-Prieto B, Bolbrinker J, Stucchi P, de Las Heras AI, Merino B, Arribas S, Ruiz-Gayo M, Huber M, Wehland M, Kreutz R, Fernandez-Alfonso MS (2008) Comparative expression analysis of the renin–angiotensin system components between white and brown perivascular adipose tissue. J Endocrinol 197(1):55–64. https://doi.org/10.1677/JOE-07-0284

    Article  CAS  PubMed  Google Scholar 

  101. Ozen G, Daci A, Norel X, Topal G (2015) Human perivascular adipose tissue dysfunction as a cause of vascular disease: focus on vascular tone and wall remodeling. Eur J Pharmacol 766:16–24. https://doi.org/10.1016/j.ejphar.2015.09.012

    Article  CAS  PubMed  Google Scholar 

  102. Rittig K, Dolderer JH, Balletshofer B, Machann J, Schick F, Meile T, Kuper M, Stock UA, Staiger H, Machicao F, Schaller HE, Konigsrainer A, Haring HU, Siegel-Axel DI (2012) The secretion pattern of perivascular fat cells is different from that of subcutaneous and visceral fat cells. Diabetologia 55(5):1514–1525. https://doi.org/10.1007/s00125-012-2481-9

    Article  CAS  PubMed  Google Scholar 

  103. Chatterjee TK, Stoll LL, Denning GM, Harrelson A, Blomkalns AL, Idelman G, Rothenberg FG, Neltner B, Romig-Martin SA, Dickson EW, Rudich S, Weintraub NL (2009) Proinflammatory phenotype of perivascular adipocytes: influence of high-fat feeding. Circ Res 104(4):541–549. https://doi.org/10.1161/CIRCRESAHA.108.182998

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  104. Thanassoulis G, Massaro JM, Corsini E, Rogers I, Schlett CL, Meigs JB, Hoffmann U, O’Donnell CJ, Fox CS (2012) Periaortic adipose tissue and aortic dimensions in the Framingham Heart Study. J Am Heart Assoc 1(6):e000885. https://doi.org/10.1161/JAHA.112.000885

    Article  PubMed  PubMed Central  Google Scholar 

  105. Fox CS, Massaro JM, Schlett CL, Lehman SJ, Meigs JB, O’Donnell CJ, Hoffmann U, Murabito JM (2010) Periaortic fat deposition is associated with peripheral arterial disease: the Framingham heart study. Circ Cardiovasc Imaging 3(5):515–519. https://doi.org/10.1161/CIRCIMAGING.110.958884

    Article  PubMed  PubMed Central  Google Scholar 

  106. Foster MC, Hwang SJ, Porter SA, Massaro JM, Hoffmann U, Fox CS (2011) Fatty kidney, hypertension, and chronic kidney disease: the Framingham Heart Study. Hypertension 58(5):784–790. https://doi.org/10.1161/HYPERTENSIONAHA.111.175315

    Article  CAS  PubMed  Google Scholar 

  107. Wagner R, Machann J, Lehmann R, Rittig K, Schick F, Lenhart J, Artunc F, Linder K, Claussen CD, Schleicher E, Fritsche A, Haring HU, Weyrich P (2012) Exercise-induced albuminuria is associated with perivascular renal sinus fat in individuals at increased risk of type 2 diabetes. Diabetologia 55(7):2054–2058. https://doi.org/10.1007/s00125-012-2551-z

    Article  CAS  PubMed  Google Scholar 

  108. Chughtai HL, Morgan TM, Rocco M, Stacey B, Brinkley TE, Ding J, Nicklas B, Hamilton C, Hundley WG (2010) Renal sinus fat and poor blood pressure control in middle-aged and elderly individuals at risk for cardiovascular events. Hypertension 56(5):901–906. https://doi.org/10.1161/HYPERTENSIONAHA.110.157370

    Article  CAS  PubMed  Google Scholar 

  109. Montani JP, Carroll JF, Dwyer TM, Antic V, Yang Z, Dulloo AG (2004) Ectopic fat storage in heart, blood vessels and kidneys in the pathogenesis of cardiovascular diseases. Int J Obes Relat Metab Disord 28 Suppl 4:S58–S65. https://doi.org/10.1038/sj.ijo.0802858

    Article  CAS  PubMed  Google Scholar 

  110. Vettor R, Milan G, Franzin C, Sanna M, De Coppi P, Rizzuto R, Federspil G (2009) The origin of intermuscular adipose tissue and its pathophysiological implications. Am J Physiol Endocrinol Metab 297(5):E987–E998. https://doi.org/10.1152/ajpendo.00229.2009

    Article  CAS  PubMed  Google Scholar 

  111. Marcus RL, Addison O, Kidde JP, Dibble LE, Lastayo PC (2010) Skeletal muscle fat infiltration: impact of age, inactivity, and exercise. J Nutr Health Aging 14(5):362–366

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  112. Addison O, Marcus RL, Lastayo PC, Ryan AS (2014) Intermuscular fat: a review of the consequences and causes. Int J Endocrinol 2014:309570. https://doi.org/10.1155/2014/309570

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  113. Kim JH, Jung MH, Lee JM, Son HS, Cha BY, Chang SA (2012) Diabetic peripheral neuropathy is highly associated with nontraumatic fractures in Korean patients with type 2 diabetes mellitus. Clin Endocrinol (Oxf) 77(1):51–55. https://doi.org/10.1111/j.1365-2265.2011.04222.x

    Article  Google Scholar 

  114. Gallagher D, Kuznia P, Heshka S, Albu J, Heymsfield SB, Goodpaster B, Visser M, Harris TB (2005) Adipose tissue in muscle: a novel depot similar in size to visceral adipose tissue. Am J Clin Nutr 81(4):903–910 pii]

    Article  CAS  PubMed  Google Scholar 

  115. Gallagher D, Kelley DE, Yim JE, Spence N, Albu J, Boxt L, Pi-Sunyer FX, Heshka S (2009) Adipose tissue distribution is different in type 2 diabetes. Am J Clin Nutr 89(3):807–814. https://doi.org/10.3945/ajcn.2008.26955

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  116. Ribeiro RJ, Monteiro CP, Cunha VF, Azevedo AS, Oliveira MJ, Monteiro R, Fraga AM, Principe P, Lobato C, Lobo F, Morais A, Silva V, Sanches-Magalhaes J, Oliveira J, Guimaraes JT, Lopes CM, Medeiros RM (2012) Tumor cell-educated periprostatic adipose tissue acquires an aggressive cancer-promoting secretory profile. Cell Physiol Biochem 29(1–2):233–240. https://doi.org/10.1159/000337604

    Article  CAS  PubMed  Google Scholar 

  117. Ribeiro R, Monteiro C, Catalan V, Hu P, Cunha V, Rodriguez A, Gomez-Ambrosi J, Fraga A, Principe P, Lobato C, Lobo F, Morais A, Silva V, Sanches-Magalhaes J, Oliveira J, Pina F, Lopes C, Medeiros R, Fruhbeck G (2012) Obesity and prostate cancer: gene expression signature of human periprostatic adipose tissue. BMC Med 10:108. https://doi.org/10.1186/1741-7015-10-108

    Article  PubMed  PubMed Central  Google Scholar 

  118. Freedland SJ, Banez LL, Sun LL, Fitzsimons NJ, Moul JW (2009) Obese men have higher-grade and larger tumors: an analysis of the duke prostate center database. Prostate Cancer Prostatic Dis 12(3):259–263. https://doi.org/10.1038/pcan.2009.11

    Article  CAS  PubMed  Google Scholar 

  119. Hamrick MW, McGee-Lawrence ME, Frechette DM (2016) Fatty infiltration of skeletal muscle: mechanisms and comparisons with bone marrow adiposity. Front Endocrinol (Lausanne) 7:69. https://doi.org/10.3389/fendo.2016.00069

    Article  Google Scholar 

  120. Hardouin P, Rharass T, Lucas S (2016) Bone marrow adipose tissue: to be or not to be a typical adipose tissue? Front Endocrinol (Lausanne) 7:85. https://doi.org/10.3389/fendo.2016.00085

    Article  Google Scholar 

  121. Sadie-Van Gijsen H, Crowther NJ, Hough FS, Ferris WF (2013) The interrelationship between bone and fat: from cellular see-saw to endocrine reciprocity. Cell Mol Life Sci 70(13):2331–2349. https://doi.org/10.1007/s00018-012-1211-2

    Article  CAS  PubMed  Google Scholar 

  122. Iwaniec UT, Turner RT (2013) Failure to generate bone marrow adipocytes does not protect mice from ovariectomy-induced osteopenia. Bone 53(1):145–153. https://doi.org/10.1016/j.bone.2012.11.034

    Article  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Systems Medicine, University of Rome Tor Vergata, Via Montpellier 1, 00133, Rome, Italy

    Valeria Guglielmi & Paolo Sbraccia

  2. Internal Medicine Unit and Obesity Center, University Hospital Policlinico Tor Vergata, Rome, Italy

    Valeria Guglielmi & Paolo Sbraccia

Authors
  1. Valeria Guglielmi
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Paolo Sbraccia
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Valeria Guglielmi.

Ethics declarations

Funding

This work was supported by a Grant from the Ministero della Salute (Project no. 45/RF-2013-02357791).

Conflict of interest

Valeria Guglielmi declares that she has no conflict of interest. Paolo Sbraccia declares that he has no conflict of interest.

Ethical approval

This article does not contain any studies with human participants or animals performed by any of the authors.

Additional information

This article is part of the topical collection on Italian Society of Obesity’s Reviews.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Guglielmi, V., Sbraccia, P. Obesity phenotypes: depot-differences in adipose tissue and their clinical implications. Eat Weight Disord 23, 3–14 (2018). https://doi.org/10.1007/s40519-017-0467-9

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s40519-017-0467-9

Keywords

Search

Navigation