Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Article
  • Published:

Epidemiology and Population Health

Participation of white adipose tissue dysfunction on circulating HDL cholesterol and HDL particle size in apparently healthy humans

International Journal of Obesity volume 44, pages 920–928 (2020)Cite this article

Subjects

Abstract

Objective

To use the combined presence of the elevated insulin resistance index in adipose tissue (Adipo-IR) and low values of adiponectin as a marker of dysfunctional adipose tissue, and to analyze its possible association with low values of high-density lipoprotein cholesterol (HDL-C) and small size of HDL particles.

Research design and methods

The analysis included 253 subjects with functional adipose tissue and 253 with dysfunctional adipose tissue, considering similar gender, age, and body mass index (BMI). Adipo-IR was considered when index values (free fatty acids × insulin concentrations) were ≥75th percentile. Low levels of adiponectin were considered when concentration in serum was <25th percentile (determined by ELISA). HDL size was estimated by a quantitative validated equation. Small HDL size was considered when values were <25th percentile.

Results

When comparing subjects with functional adipose tissue with those of dysfunctional adipose tissue, the latter had a higher prevalence of low HDL-C (51.4% vs. 64.0%; p = 0.004) and small HDL (56.9% vs. 67.6%; p = 0.009). Multivariate analysis indicated that independently from other metabolic risk factors, dysfunction of adipose tissue is significantly associated with low HDL-C (OR: 1.624 [CI 95%: 1.100–2.397]) and small HDL (OR: 1.462 [CI 95%: 1.000–2.139]). Adding BMI, waist circumference, and subcutaneous or visceral adipose tissue did not modify the association.

Conclusions

Dysfunction of adipose tissue is associated with a 65 and 50% higher probability of having low HDL-C and small HDL. Identification of dysfunctional adipose tissue could be a useful tool in the clinical setting to prevent the cardiometabolic risk independently from adiposity.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Fig. 1
Fig. 2
Fig. 3
Fig. 4

Similar content being viewed by others

References

  1. Gustafson B. Adipose tissue, inflammation and atherosclerosis. J Atheroscler Thromb. 2010;17:332–41.

    CAS  PubMed  Google Scholar 

  2. Krause BR, Hartman AD. Adipose tissue and cholesterol metabolism. J Lipid Res. 1984;25:97–110.

    CAS  PubMed  Google Scholar 

  3. Hammarstedt A, Gogg S, Hedjazifar S, Nerstedt A, Smith U. Impaired adipogenesis and dysfunctional adipose tissue in human hypertrophic obesity. Physiol Rev. 2018;98:1911–41.

    CAS  PubMed  Google Scholar 

  4. Armani A, Berry A, Cirulli F, Caprio M. Molecular mechanisms underlying metabolic syndrome: the expanding role of the adipocyte. FASEB J. 2017;31:4240–55.

    CAS  PubMed  Google Scholar 

  5. Gastaldelli A, Gaggini M, DeFronzo RA. Role of adipose tissue insulin resistance in the natural history of type 2 diabetes: results from the San Antonio Metabolism Study. Diabetes. 2017;66:815–22.

    PubMed  Google Scholar 

  6. Huang JP, Hsu SC, Meir YJ, Hsieh PS, Chang CC, Chen KH, et al. Role of dysfunctional adipocytes in cholesterol-induced nonobese metabolic syndrome. J Mol Endocrinol. 2018;60:307–21.

    PubMed  Google Scholar 

  7. Zhang Y, McGillicuddy FC, Hinkle CC, O’Neill S, Glick JM, Rothblat GH, et al. Adipocyte modulation of high-density lipoprotein cholesterol. Circulation. 2010;121:1347–55.

    CAS  PubMed  PubMed Central  Google Scholar 

  8. Chung S, Sawyer JK, Gebre AK, Maeda N, Parks JS. Adipose tissue ATP binding cassette transporter A1 contributes to high-density lipoprotein biogenesis in vivo. Circulation. 2011;124:1663–72.

    CAS  PubMed  PubMed Central  Google Scholar 

  9. Holland WL, Miller RA, Wang ZV, Sun K, Barth BM, Bui HH, et al. Receptor-mediated activation of ceramidase activity initiates the pleiotropic actions of adiponectin. Nat Med. 2011;17:55–63.

    CAS  PubMed  Google Scholar 

  10. Gordon T, Castelli WP, Hjortland MC, Kannel WB, Dawber TR. The Framingham Study. High density lipoprotein as a protective factor against coronary heart disease. Am J Med. 1977;62:707–14.

    CAS  PubMed  Google Scholar 

  11. Kelley DE, Williams KV, Price JC, McKolanis TM, Goodpaster BH, Thaete FL. Plasma fatty acids, adiposity, and variance of skeletal muscle insulin resistance in type 2 diabetes mellitus. J Clin Endocrinol Metab. 2001;86:5412–9.

    CAS  PubMed  Google Scholar 

  12. Iqbal F, Baker WS, Khan MI, Thukuntla S, McKinney KH, Abate N, et al. Current and future therapies for addressing the effects of inflammation on HDL cholesterol metabolism. Br J Pharmacol. 2017;174:3986–4006.

    CAS  PubMed  PubMed Central  Google Scholar 

  13. Pérez-Méndez O, Torres-Tamayo M, Posadas-Romero C, Vidaure Garcés V, Carreón-Torres E, Mendoza-Pérez E, et al. Abnormal HDL subclasses distribution in overweight children with insulin resistance or type 2 diabetes mellitus. Clin Chim Acta. 2007;376:17–22.

    PubMed  Google Scholar 

  14. Hansel B, Giral P, Nobecourt E, Chantepie S, Bruckert E, Chapman MJ, et al. Metabolic syndrome is associated with elevated oxidative stress and dysfunctional dense high-density lipoprotein particles displaying impaired antioxidative activity. J Clin Endocrinol Metab. 2004;89:4963–71.

    CAS  PubMed  Google Scholar 

  15. Medina-Urrutia A, Juárez-Rojas JG, Cardoso-Saldaña G, Jorge-Galarza E, Posadas-Sánchez R, Martínez-Alvarado R, et al. Abnormal high-density lipoproteins in overweight adolescents with atherogenic dyslipidemia. Pediatrics. 2011;127:e1521–1527.

    PubMed  Google Scholar 

  16. Medina-Urrutia A, Juárez-Rojas JG, Martínez-Alvarado R, Jorge-Galarza E, Posadas-Sánchez R, Caracas-Portilla N, et al. High-density lipoprotein subclasses distribution and composition in Mexican adolescents with low HDL cholesterol and/or high triglyceride concentrations, and its association with insulin and C-reactive protein. Atherosclerosis. 2008;201:392–7.

    CAS  PubMed  Google Scholar 

  17. Twig G, Afek A, Derazne E, Tzur D, Cukierman-Yaffe T, Gerstein HC, et al. Diabetes risk among overweight and obese metabolically healthy young adults. Diabetes Care. 2014;37:2989–95.

    CAS  PubMed  Google Scholar 

  18. Phillips CM, Perry IJ. Does inflammation determine metabolic health status in obese and nonobese adults? J Clin Endocrinol Metab. 2013;98:E1610–E1619.

    CAS  PubMed  Google Scholar 

  19. Hammarstedt A, Graham TE, Kahn BB. Adipose tissue dysregulation and reduced insulin sensitivity in non-obese individuals with enlarged abdominal adipose cells. Diabetol Metab Syndr. 2012;4:42.

    CAS  PubMed  PubMed Central  Google Scholar 

  20. Henninger AM, Eliasson B, Jenndahl LE, Hammarstedt A. Adipocyte hypertrophy, inflammation and fibrosis characterize subcutaneous adipose tissue of healthy, non- obese subjects predisposed to type 2 diabetes. PLoS ONE. 2014;9:e105262.

    PubMed  PubMed Central  Google Scholar 

  21. Lotta LA, Gulati P, Day FR, Payne F, Ongen H, van de Bunt M, et al. Integrative genomic analysis implicates limited peripheral adipose storage capacity in the pathogenesis of human insulin resistance. Nat Genet. 2017;49:17–26.

    CAS  PubMed  Google Scholar 

  22. Scott RA, Fall T, Pasko D, Barker A, Sharp SJ, Arriola L, et al. Common genetic variants highlight the role of insulin resistance and body fat distribution in type 2 diabetes, independent of obesity. Diabetes. 2014;63:4378–87.

    CAS  PubMed  PubMed Central  Google Scholar 

  23. St-Onge MP, Janssen I, Heymsfield SB. Metabolic syndrome in normal-weight Americans: new definition of the metabolically obese, normal-weight individual. Diabetes Care. 2004;27:2222–8.

    PubMed  Google Scholar 

  24. Gastaldelli A, Miyazaki Y, Mahankali A, Berria R, Pettiti M, Buzzigoli E, et al. The effect of pioglitazone on the liver: role of adiponectin. Diabetes Care. 2006;29:2275–81.

    CAS  PubMed  Google Scholar 

  25. Bajaj M, Suraamornkul S, Piper P, Hardies LJ, Glass L, Cersosimo E, et al. Decreased plasma adiponectin concentrations are closely related to hepatic fat content and hepatic insulin resistance in pioglitazone-treated type 2 diabetic patients. J Clin Endocrinol Metab. 2004;89:200–6.

    CAS  PubMed  Google Scholar 

  26. Kim JY, Bacha F, Tfayli H, Michaliszyn SF, Yousuf S, Arslanian S. Adipose tissue insulin resistance in youth on the spectrum from normal weight to obese and from normal glucose tolerance to impaired glucose tolerance to type 2 diabetes. Diabetes Care. 2019;42:265–72.

    CAS  PubMed  Google Scholar 

  27. Zhan C, Shi M, Yang Y, Pang H, Fei S, Bai L, et al. Prevalence and risk factors of carotid plaque among middle-aged and elderly adults in rural Tianjin, China. Sci Rep. 2016;6:23870.

    CAS  PubMed  PubMed Central  Google Scholar 

  28. Baecke JA, Burema J, Frijters JE. A short questionnaire for the measurement of habitual physical activity in epidemiological studies. Am J Clin Nutr. 1982;36:936–42.

    CAS  PubMed  Google Scholar 

  29. Sánchez-Castillo CP, Velázquez-Monroy O, Berber A, Lara-Esqueda A, Tapia-Conyer R, James WP. Anthropometric cutoff points for predicting chronic diseases in the Mexican National Health Survey 2000. Obes Res. 2003;11:442–51.

    PubMed  Google Scholar 

  30. DeLong DM, DeLong ER, Wood PD, Lippel K, Rifkind BM. A comparison of methods for the estimation of plasma low- and very low-density lipoprotein cholesterol. The Lipid Research Clinics Prevalence Study. JAMA. 1986;256:2372–7.

    CAS  PubMed  Google Scholar 

  31. Mazer NA, Giulianini F, Paynter NP, Jordan P, Mora S. A comparison of the theoretical relationship between HDL size and the ratio of HDL cholesterol to apolipoprotein A-I with experimental results from the Women’s Health Study. Clin Chem. 2013;59:949–58.

    CAS  PubMed  PubMed Central  Google Scholar 

  32. Medina-Urrutia A, Posadas-Romero C, Jorge-Galarza E, López-Uribe AR, González-Salazar MC, Juárez-Rojas JG. Inflammasome activation markers are independently associated with hypoalphalipoproteinemia in a Mexican-Mestizo population. Clin Investig. 2018;8:113–21.

    Google Scholar 

  33. Maurovich-Horvat P, Massaro J, Fox CS, Moselewski F, O’Donnell CJ, Hoffmann U. Comparison of anthropometric, area- and volume-based assessment of abdominal subcutaneous and visceral adipose tissue volumes using multi-detector computed tomography. Int J Obes. 2007;31:500–6.

    CAS  Google Scholar 

  34. Kvist H, Chowdhury B, Grangård U, Tylén U, Sjöström L. Total and visceral adipose-tissue volumes derived from measurements with computed tomography in adult men and women: predictive equations. Am J Clin Nutr. 1988;48:1351–61.

    CAS  PubMed  Google Scholar 

  35. Yang RZ, Lee MJ, Hu H, Pollin TI, Ryan AS, Nicklas BJ, et al. Acute-phase serum amyloid A: an inflammatory adipokine and potential link between obesity and its metabolic complications. Plos Med. 2006;3:e287.

    PubMed  PubMed Central  Google Scholar 

  36. Khan UI, Ogorodnikova AD, Xu L, Wang D, Wassertheil-Smoller S, Ho GY, et al. The adipokine profile of metabolically benign obese and at-risk normal weight postmenopausal women: the Women’s Health Initiative Observational Study. Obesity. 2014;22:786–94.

    CAS  PubMed  Google Scholar 

  37. Gray SL, Vidal-Puig AJ. Adipose tissue expandability in the maintenance of metabolic homeostasis. Nutr Rev. 2007;65:S7–S12.

    PubMed  Google Scholar 

  38. Després JP, Lemieux I, Bergeron J, Pibarot P, Mathieu P, Larose E, et al. Abdominal obesity and the metabolic syndrome: contribution to global cardiometabolic risk. Arterioscler Thromb Vasc Biol. 2008;28:1039–49.

    PubMed  Google Scholar 

  39. Miyazaki Y, Glass L, Triplitt C, Matsuda M, Cusi K, Mahankali A, et al. Effect of rosiglitazone on glucose and non-esterified fatty acid metabolism in type II diabetic patients. Diabetologia. 2001;44:2210–9.

    CAS  PubMed  Google Scholar 

  40. Rader DJ, Hovingh GK. HDL and cardiovascular disease. Lancet. 2014;384:618–25.

    CAS  PubMed  Google Scholar 

  41. Mora S. Advanced lipoprotein testing and subfractionation are not (yet) ready for routine clinical use. Circulation. 2009;119:2396–404.

    PubMed  PubMed Central  Google Scholar 

  42. Sondergaard E, Espinosa De Ycaza AE, Morgan-Bathke M, Jensen MD. How to measure adipose tissue insulin sensitivity. J Clin Endocrinol Metab. 2017;102:1193–9.

    PubMed  PubMed Central  Google Scholar 

Download references

Acknowledgements

This study was partially supported by Mexico´s Consejo Nacional de Ciencia y Tecnología (Project no. SALUD-2010-2-150537) and Instituto Nacional de Cardiología Ignacio Chávez (Project no. 17-1040).

Author information

Authors and Affiliations

  1. Department of Endocrinology, Instituto Nacional de Cardiología Ignacio Chávez, Mexico City, Mexico

    Juan G. Juárez-Rojas, Aida X. Medina-Urrutia, Juan Reyes-Barrera, Carlos Posadas-Romero, Alejandro Macías-Cruz & Esteban Jorge-Galarza

  2. Department of Nutrition Physiology, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City, Mexico

    Ivan Torre-Villalvazo

  3. Department of Cardiothoracic Surgery, Instituto Nacional de Cardiología Ignacio Chávez, Mexico City, Mexico

    Víctor H. Sainz-Escárrega

Authors
  1. Juan G. Juárez-Rojas
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Ivan Torre-Villalvazo
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Aida X. Medina-Urrutia
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Juan Reyes-Barrera
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Víctor H. Sainz-Escárrega
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Carlos Posadas-Romero
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Alejandro Macías-Cruz
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Esteban Jorge-Galarza
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

JGJR conceived the project, researched data, contributed to discussion, and wrote the manuscript. ITV provided critical review and revision, and contributed to discussion. AXMU, JRB, VHSE, CPR, and AMC researched data and contributed to discussion. CPR and EJG conceived the project, contributed to discussion, and provided critical review and revision. JGJR is the guarantor of this work and, as such, had full access to all the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis.

Corresponding author

Correspondence to Esteban Jorge-Galarza.

Ethics declarations

Conflict of interest

The authors declare they have no conflict of interest.

Additional information

Publisher’s note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Juárez-Rojas, J.G., Torre-Villalvazo, I., Medina-Urrutia, A.X. et al. Participation of white adipose tissue dysfunction on circulating HDL cholesterol and HDL particle size in apparently healthy humans. Int J Obes 44, 920–928 (2020). https://doi.org/10.1038/s41366-019-0493-y

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/s41366-019-0493-y

This article is cited by

Search

Advanced search

Quick links