Jump to ContentJump to Main Navigation
Show Summary Details
More options …

Hormone Molecular Biology and Clinical Investigation

Editor-in-Chief: Chetrite, Gérard S.

Editorial Board: Alexis, Michael N. / Baniahmad, Aria / Beato, Miguel / Bouillon, Roger / Brodie, Angela / Carruba, Giuseppe / Chen, Shiuan / Cidlowski, John A. / Clarke, Robert / Coelingh Bennink, Herjan J.T. / Darbre, Philippa D. / Drouin, Jacques / Dufau, Maria L. / Edwards, Dean P. / Falany, Charles N. / Fernandez-Perez, Leandro / Ferroud, Clotilde / Feve, Bruno / Flores-Morales, Amilcar / Foster, Michelle T. / Garcia-Segura, Luis M. / Gastaldelli, Amalia / Gee, Julia M.W. / Genazzani, Andrea R. / Greene, Geoffrey L. / Groner, Bernd / Hampl, Richard / Hilakivi-Clarke, Leena / Hubalek, Michael / Iwase, Hirotaka / Jordan, V. Craig / Klocker, Helmut / Kloet, Ronald / Labrie, Fernand / Mendelson, Carole R. / Mück, Alfred O. / Nicola, Alejandro F. / O'Malley, Bert W. / Raynaud, Jean-Pierre / Ruan, Xiangyan / Russo, Jose / Saad, Farid / Sanchez, Edwin R. / Schally, Andrew V. / Schillaci, Roxana / Schindler, Adolf E. / Söderqvist, Gunnar / Speirs, Valerie / Stanczyk, Frank Z. / Starka, Luboslav / Sutter, Thomas R. / Tresguerres, Jesús A. / Wahli, Walter / Wildt, Ludwig / Yang, Kaiping / Yu, Qi


CiteScore 2018: 2.43

SCImago Journal Rank (SJR) 2018: 0.947
Source Normalized Impact per Paper (SNIP) 2018: 0.837

Online
ISSN
1868-1891
See all formats and pricing
More options …
Volume 33, Issue 2

Issues

Neck adipose tissue – tying ties in metabolic disorders

Vlatka Pandzic Jaksic
  • Corresponding author
  • Department of Endocrinology, Dubrava University Hospital, Av. G. Šuška 6, 10000 Zagreb, Croatia
  • Email
  • Other articles by this author:
  • De Gruyter OnlineGoogle Scholar
/ Danijela Grizelj / Ana Livun / Drago Boscic / Marko Ajduk / Rajko Kusec
  • Department of Molecular Biology, Dubrava University Hospital, 10000 Zagreb, Croatia
  • Department of Hematology, Dubrava University Hospital, 10000 Zagreb, Croatia
  • Other articles by this author:
  • De Gruyter OnlineGoogle Scholar
/ Ozren Jaksic
Published Online: 2018-02-09 | DOI: https://doi.org/10.1515/hmbci-2017-0075

Abstract

Upper body adipose tissue accumulation has been associated with clustering of metabolic disorders and increased cardiovascular risk. Neck circumference (NC) indicated that subcutaneous adipose tissue (SAT) in that region is an independent pathogenic depot that might account for the additional risk missed by visceral adipose tissue (VAT). Neck adipose tissue (NAT) is not only one more ectopic depot but has several particular features that might modulate its metabolic role. Besides a controversial impact on obstructive apnea syndrome, neck fat encompasses carotid arteries as an important perivascular adipose tissue (PVAT) depot. With dysfunctional changes in obesity, physiologic vascular regulation is lost and inflammatory signals accelerate atherogenesis. Unexpected was the discovery of brown and beige adipocytes in the neck of human adults. When stimulated, brown adipose tissue (BAT) dissipates energy through thermogenesis and it is associated with other favorable metabolic effects. Moreover, the neck is the region where the browning mechanism was disclosed. With this unique plastic nature, NAT revealed multiple ties, challenging dynamics and potential new therapeutic targets that might have significant implications on metabolic outcomes and vascular risk.

Keywords: adipose tissue; brown; neck; perivascular; subcutaneous

References

  • [1]

    Haslam D. Obesity: a medical history. Obes Rev. 2007;8:31–6.CrossrefPubMedGoogle Scholar

  • [2]

    Vague J. La differentiation sexuelle, facteur determinant des formes de robeslte. La Presse medicale. 1947;55:339.Google Scholar

  • [3]

    Despres JP, Moorjani S, Lupien PJ, Tremblay A, Nadeau A, Bouchard C. Regional distribution of body fat, plasma lipoproteins, and cardiovascular disease. Arteriosclerosis (Dallas, Tex). 1990;10:497–511.CrossrefPubMedGoogle Scholar

  • [4]

    Kannel WB, Cupples LA, Ramaswami R, Stokes J, 3rd, Kreger BE, Higgins M. Regional obesity and risk of cardiovascular disease; the Framingham Study. J Clin Epidemiol. 1991;44:183–90.CrossrefPubMedGoogle Scholar

  • [5]

    Wronska A, Kmiec Z. Structural and biochemical characteristics of various white adipose tissue depots. Acta Physiol (Oxford, UK). 2012;205:194–208.CrossrefGoogle Scholar

  • [6]

    Goodpaster BH, Krishnaswami S, Harris TB, Katsiaras A, Kritchevsky SB, Simonsick EM, et al. Obesity, regional body fat distribution, and the metabolic syndrome in older men and women. Arch Intern Med. 2005;165:777–83.PubMedCrossrefGoogle Scholar

  • [7]

    Matsuzawa Y. The role of fat topology in the risk of disease. Int J Obes. 2008;32:S83–92.CrossrefGoogle Scholar

  • [8]

    Karastergiou K, Smith SR, Greenberg AS, Fried SK. Sex differences in human adipose tissues – the biology of pear shape. Biol Sex Differ. 2012;3:13.PubMedCrossrefGoogle Scholar

  • [9]

    Pandzic Jaksic V, Grizelj D. Under the surface of subcutaneous adipose tissue biology. Acta Dermatovenerol Croat. 2016;24:250–60.PubMedGoogle Scholar

  • [10]

    Ben-Noun L, Sohar E, Laor A. Neck circumference as a simple screening measure for identifying overweight and obese patients. Obes Res. 2001;9:470–7.PubMedCrossrefGoogle Scholar

  • [11]

    Stabe C, Vasques AC, Lima MM, Tambascia MA, Pareja JC, Yamanaka A, et al. Neck circumference as a simple tool for identifying the metabolic syndrome and insulin resistance: results from the Brazilian Metabolic Syndrome Study. Clin Endocrinol (Oxf). 2013;78:874–81.CrossrefPubMedGoogle Scholar

  • [12]

    Sjostrom CD, Hakangard AC, Lissner L, Sjostrom L. Body compartment and subcutaneous adipose tissue distribution--risk factor patterns in obese subjects. Obes Res. 1995;3:9–22.CrossrefGoogle Scholar

  • [13]

    Ben-Noun L, Laor A. Relationship of neck circumference to cardiovascular risk factors. Obes Res. 2003;11:226–31.PubMedCrossrefGoogle Scholar

  • [14]

    Yang GR, Yuan SY, Fu HJ, Wan G, Zhu LX, Bu XL, et al. Neck circumference positively related with central obesity, overweight, and metabolic syndrome in Chinese subjects with type 2 diabetes: Beijing Community Diabetes Study 4. Diabetes Care. 2010;33:2465–7.CrossrefPubMedGoogle Scholar

  • [15]

    Huang BX, Zhu MF, Wu T, Zhou JY, Liu Y, Chen XL, et al. Neck circumference, along with other anthropometric indices, has an independent and additional contribution in predicting fatty liver disease. PLoS One. 2015;10:e0118071.CrossrefPubMedGoogle Scholar

  • [16]

    Fitch KV, Stanley TL, Looby SE, Rope AM, Grinspoon SK. Relationship between neck circumference and cardiometabolic parameters in HIV-infected and non-HIV-infected adults. Diabetes Care. 2011;34:1026–31.PubMedCrossrefGoogle Scholar

  • [17]

    Dai Y, Wan X, Li X, Jin E, Li X. Neck circumference and future cardiovascular events in a high-risk population – A prospective cohort study. Lipids Health Dis. 2016;15:46.CrossrefGoogle Scholar

  • [18]

    Preis SR, Massaro JM, Hoffmann U, D’Agostino RB, Sr., Levy D, Robins SJ, et al. Neck circumference as a novel measure of cardiometabolic risk: the Framingham Heart study. J Clin Endocrinol Metab. 2010;95:3701–10.PubMedCrossrefGoogle Scholar

  • [19]

    Mittendorfer B. Origins of metabolic complications in obesity: adipose tissue and free fatty acid trafficking. Curr Opin Clin Nutr Metab Care. 2011;14:535–41.PubMedCrossrefGoogle Scholar

  • [20]

    Rosenquist KJ, Therkelsen KE, Massaro JM, Hoffmann U, Fox CS. Development and reproducibility of a computed tomography-based measurement for upper body subcutaneous neck fat. J Am Heart Assoc. 2014;3:e000979.CrossrefPubMedGoogle Scholar

  • [21]

    Torriani M, Gill CM, Daley S, Oliveira AL, Azevedo DC, Bredella MA. Compartmental neck fat accumulation and its relation to cardiovascular risk and metabolic syndrome. Am J Clin Nutr. 2014;100:1244–51.CrossrefPubMedGoogle Scholar

  • [22]

    Shigeta Y, Enciso R, Ogawa T, Ikawa T, Clark GT. Cervical CT derived neck fat tissue distribution differences in Japanese males and females and its effect on retroglossal and retropalatal airway volume. Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 2008;106:275–84.CrossrefPubMedGoogle Scholar

  • [23]

    Cypess AM, White AP, Vernochet C, Schulz TJ, Xue R, Sass CA, et al. Anatomical localization, gene expression profiling and functional characterization of adult human neck brown fat. Nat Med. 2013;19:635–9.PubMedCrossrefGoogle Scholar

  • [24]

    Maresky HS, Sharfman Z, Ziv-Baran T, Gomori JM, Copel L, Tal S. Anthropometric assessment of neck adipose tissue and airway volume using multidetector computed tomography: an imaging approach and association with overall mortality. Medicine (Baltimore). 2015;94:e1991.PubMedCrossrefGoogle Scholar

  • [25]

    Lee JJ, Pedley A, Therkelsen KE, Hoffmann U, Massaro JM, Levy D, et al. Upper body subcutaneous fat is associated with cardiometabolic risk factors. Am J Med. 2017;130:958–66 e1.Google Scholar

  • [26]

    Martin ML, Jensen MD. Effects of body fat distribution on regional lipolysis in obesity. Eur J Clin Invest. 1991;88:609–13.CrossrefGoogle Scholar

  • [27]

    Guo Z, Hensrud DD, Johnson CM, Jensen MD. Regional postprandial fatty acid metabolism in different obesity phenotypes. Diabetes. 1999;48:1586–92.CrossrefPubMedGoogle Scholar

  • [28]

    Romero-Corral A, Caples SM, Lopez-Jimenez F, Somers VK. Interactions between obesity and obstructive sleep apnea: implications for treatment. Chest. 2010;137:711–9.PubMedCrossrefGoogle Scholar

  • [29]

    Garg A. Acquired and inherited lipodystrophies. N Engl J Med. 2004;350:1220–34.PubMedCrossrefGoogle Scholar

  • [30]

    Chen K, Xie Y, Hu P, Zhao S, Mo Z. Multiple symmetric lipomatosis: substantial subcutaneous adipose tissue accumulation did not induce glucose and lipid metabolism dysfunction. Ann Nutr Metab. 2010;57:68–73.PubMedCrossrefGoogle Scholar

  • [31]

    Fox CS, Massaro JM, Schlett CL, Lehman SJ, Meigs JB, O’Donnell CJ, et al. Periaortic fat deposition is associated with peripheral arterial disease: the Framingham heart study. Circ Cardiovasc Imaging. 2010;3:515–9.PubMedCrossrefGoogle Scholar

  • [32]

    Rosenquist KJ, Massaro JM, Pencina KM, D’Agostino RB, Beiser A, O’Connor GT, et al. Neck circumference, carotid wall intima-media thickness, and incident stroke. Diabetes Care. 2013;36:e153–4.PubMedCrossrefGoogle Scholar

  • [33]

    Baena CP, Lotufo PA, Santos IS, Goulart AC, Bittencourt MS, Duncan BB, et al. Neck circumference is associated with carotid intimal-media thickness but not with coronary artery calcium: Results from The ELSA-Brasil. Nutr Metab Cardiovasc Dis. 2016;26:216–22.CrossrefPubMedGoogle Scholar

  • [34]

    Alexopoulos N, McLean DS, Janik M, Arepalli CD, Stillman AE, Raggi P. Epicardial adipose tissue and coronary artery plaque characteristics. Atherosclerosis. 2010;210:150–4.CrossrefPubMedGoogle Scholar

  • [35]

    Skilton MR, Serusclat A, Sethu AH, Brun S, Bernard S, Balkau B, et al. Noninvasive measurement of carotid extra-media thickness: associations with cardiovascular risk factors and intima-media thickness. JACC Cardiovasc Imaging. 2009;2:176–82.CrossrefPubMedGoogle Scholar

  • [36]

    Falk E, Thim T, Kristensen IB. Atherosclerotic plaque, adventitia, perivascular fat, and carotid imaging. JACC Cardiovasc Imaging. 2009;2:183–6.PubMedGoogle Scholar

  • [37]

    Haberka M, Gasior Z. Carotid extra-media thickness in obesity and metabolic syndrome: a novel index of perivascular adipose tissue: extra-media thickness in obesity and metabolic syndrome. Atherosclerosis. 2015;239:169–77.CrossrefPubMedGoogle Scholar

  • [38]

    Yudkin JS, Eringa E, Stehouwer CD. “Vasocrine” signalling from perivascular fat: a mechanism linking insulin resistance to vascular disease. Lancet. 2005;365:1817–20.PubMedCrossrefGoogle Scholar

  • [39]

    Xia N, Li H. The role of perivascular adipose tissue in obesity-induced vascular dysfunction. Br J Pharmacol. 2017;174:3425–42.CrossrefPubMedGoogle Scholar

  • [40]

    Eringa EC, Bakker W, van Hinsbergh VW. Paracrine regulation of vascular tone, inflammation and insulin sensitivity by perivascular adipose tissue. Vascul Pharmacol. 2012;56:204–9.PubMedCrossrefGoogle Scholar

  • [41]

    Pandzic Jaksic V, Gizdic B, Miletic Z, Trutin-Ostovic K, Jaksic O. Association of monocyte CCR2 expression with obesity and insulin resistance in postmenopausal women. Clin Invest Med. 2013;36:E24–31.CrossrefPubMedGoogle Scholar

  • [42]

    Manka D, Chatterjee TK, Stoll LL, Basford JE, Konaniah ES, Srinivasan R, et al. Transplanted perivascular adipose tissue accelerates injury-induced neointimal hyperplasia: role of monocyte chemoattractant protein-1. Arterioscler Thromb Vasc Biol. 2014;34:1723–30.PubMedCrossrefGoogle Scholar

  • [43]

    Chatterjee TK, Stoll LL, Denning GM, Harrelson A, Blomkalns AL, Idelman G, et al. Proinflammatory phenotype of perivascular adipocytes: influence of high-fat feeding. Circ Res. 2009;104:541–9.CrossrefPubMedGoogle Scholar

  • [44]

    Li C, Wang Z, Wang C, Ma Q, Zhao Y. Perivascular adipose tissue-derived adiponectin inhibits collar-induced carotid atherosclerosis by promoting macrophage autophagy. PLoS One. 2015;10:e0124031.CrossrefPubMedGoogle Scholar

  • [45]

    Mazurek T, Zhang L, Zalewski A, Mannion JD, Diehl JT, Arafat H, et al. Human epicardial adipose tissue is a source of inflammatory mediators. Circulation. 2003;108:2460–6.PubMedCrossrefGoogle Scholar

  • [46]

    Iacobellis G, Pistilli D, Gucciardo M, Leonetti F, Miraldi F, Brancaccio G, et al. Adiponectin expression in human epicardial adipose tissue in vivo is lower in patients with coronary artery disease. Cytokine. 2005;29:251–5.PubMedGoogle Scholar

  • [47]

    Sharma G, Tao M, Ding K, Yu D, King W, Deyneko G, et al. Perivascular adipose adiponectin correlates with symptom status of patients undergoing carotid endarterectomy. Stroke. 2015;46:1696–9.PubMedCrossrefGoogle Scholar

  • [48]

    Pandzic Jaksic V, Grizelj D, Marusic M, Boscic D, Ozegovic I, Vlasic A, et al. Adiponectin gene expression in subcutaneous and deep neck adipose tissue. Endocrine Abstracts. 2014;35:P785.Google Scholar

  • [49]

    Hamlat-Khennaf N, Neggazi S, Ayari H, Feugier P, Bricca G, Aouichat-Bouguerra S, et al. Inflammation in the perivascular adipose tissue and atherosclerosis. C R Biol. 2017;340:156–63.PubMedGoogle Scholar

  • [50]

    Akoumianakis I, Tarun A, Antoniades C. Perivascular adipose tissue as a regulator of vascular disease pathogenesis: identifying novel therapeutic targets. Br J Pharmacol. 2017;174:3411–24.PubMedCrossrefGoogle Scholar

  • [51]

    Nedergaard J, Bengtsson T, Cannon B. Unexpected evidence for active brown adipose tissue in adult humans. Am J Physiol Endocrinol Metab. 2007;293:E444–52.PubMedCrossrefGoogle Scholar

  • [52]

    Hao R, Yuan L, Zhang N, Li C, Yang J. Brown adipose tissue: distribution and influencing factors on FDG PET/CT scan. J Pediatr Endocrinol Metab. 2012;25:233–7.PubMedGoogle Scholar

  • [53]

    Cypess AM, Lehman S, Williams G, Tal I, Rodman D, Goldfine AB, et al. Identification and importance of brown adipose tissue in adult humans. N Engl J Med. 2009;360:1509–17.CrossrefPubMedGoogle Scholar

  • [54]

    Zingaretti MC, Crosta F, Vitali A, Guerrieri M, Frontini A, Cannon B, et al. The presence of UCP1 demonstrates that metabolically active adipose tissue in the neck of adult humans truly represents brown adipose tissue. FASEB J. 2009;23:3113–20.PubMedCrossrefGoogle Scholar

  • [55]

    van Marken Lichtenbelt WD, Vanhommerig JW, Smulders NM, Drossaerts JM, Kemerink GJ, Bouvy ND, et al. Cold-activated brown adipose tissue in healthy men. N Engl J Med. 2009;360:1500–8.CrossrefPubMedGoogle Scholar

  • [56]

    Cypess AM, Haft CR, Laughlin MR, Hu HH. Brown fat in humans: consensus points and experimental guidelines. Cell Metab. 2014;20:408–15.CrossrefPubMedGoogle Scholar

  • [57]

    Wu J, Bostrom P, Sparks LM, Ye L, Choi JH, Giang AH, et al. Beige adipocytes are a distinct type of thermogenic fat cell in mouse and human. Cell. 2012;150:366–76.PubMedCrossrefGoogle Scholar

  • [58]

    Giralt M, Villarroya F. White, brown, beige/brite: different adipose cells for different functions? Endocrinology. 2013;154:2992–3000.PubMedCrossrefGoogle Scholar

  • [59]

    Sidossis L, Kajimura S. Brown and beige fat in humans: thermogenic adipocytes that control energy and glucose homeostasis. J Clin Invest. 2015;125:478–86.CrossrefGoogle Scholar

  • [60]

    Lee P, Werner CD, Kebebew E, Celi FS. Functional thermogenic beige adipogenesis is inducible in human neck fat. Int J Obes. 2014;38:170–6.CrossrefGoogle Scholar

  • [61]

    Reddy NL, Jones TA, Wayte SC, Adesanya O, Sankar S, Yeo YC, et al. Identification of brown adipose tissue using MR imaging in a human adult with histological and immunohistochemical confirmation. J Clin Endocrinol Metab. 2014;99:E117–21.CrossrefGoogle Scholar

  • [62]

    Peirce V, Vidal-Puig A. Regulation of glucose homoeostasis by brown adipose tissue. Lancet Diabetes Endocrinol. 2013;1:353–60.CrossrefPubMedGoogle Scholar

  • [63]

    Marlatt KL, Ravussin E. Brown adipose tissue: an update on recent findings. Curr Obes Rep. 2017;6:389–96.PubMedCrossrefGoogle Scholar

  • [64]

    Aldiss P, Dellschaft N, Sacks H, Budge H, Symonds ME. Beyond obesity – thermogenic adipocytes and cardiometabolic health. Horm Mol Biol Clin Investig. 2017;31. Article id: 20170007.PubMedGoogle Scholar

  • [65]

    Chang L, Villacorta L, Li R, Hamblin M, Xu W, Dou C, et al. Loss of perivascular adipose tissue on peroxisome proliferator-activated receptor-gamma deletion in smooth muscle cells impairs intravascular thermoregulation and enhances atherosclerosis. Circulation. 2012;126:1067–78.CrossrefPubMedGoogle Scholar

  • [66]

    Chechi K, Voisine P, Mathieu P, Laplante M, Bonnet S, Picard F, et al. Functional characterization of the Ucp1-associated oxidative phenotype of human epicardial adipose tissue. Sci Rep. 2017;7:15566.CrossrefPubMedGoogle Scholar

  • [67]

    Fitzgibbons TP, Czech MP. Epicardial and perivascular adipose tissues and their influence on cardiovascular disease: basic mechanisms and clinical associations. J Am Heart Assoc. 2014;3:e000582.CrossrefPubMedGoogle Scholar

About the article

Received: 2017-10-30

Accepted: 2018-01-08

Published Online: 2018-02-09


Author Statement

Research funding: Authors state no funding involved.

Conflict of interest: Authors state no conflict of interest.

Informed consent: Informed consent is not applicable.

Ethical approval: The conducted research is not related to either human or animal use.


Citation Information: Hormone Molecular Biology and Clinical Investigation, Volume 33, Issue 2, 20170075, ISSN (Online) 1868-1891, DOI: https://doi.org/10.1515/hmbci-2017-0075.

Export Citation

©2018 Walter de Gruyter GmbH, Berlin/Boston.Get Permission

Comments (0)

Please log in or register to comment.
Log in