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.

Adipocyte and Cell Biology

A higher proportion of small adipocytes is associated with increased visceral and ectopic lipid accumulation during weight gain in response to overfeeding in men

Abstract

Background

Adipose tissue (AT) expansion occurs by hypertrophy (increase in size) and hyperplasia (increase in number) of adipocytes. The AT expandability hypothesis postulates that impaired subcutaneous AT expansion leads to ectopic fat accretion, contributing to impaired metabolic health. The role of adipogenesis as a contributing factor is debatable.

Subjects/Methods

In the present analysis, we assess changes in adipocyte size distribution in relation to changes in ectopic fat accretion in response to 8-weeks of overfeeding in 22 men (28 ± 5.4 years; BMI 25.5 ± 2.3 kg/m2) who were fed 40% over their baseline energy requirements.

Results

Participants gained 6.7 ± 2.1 kg. The percentage of small adipocytes (p = 0.03) and the peak diameter of large adipocytes (p = 0.01) increased after overfeeding. At baseline, the percentage of small adipocytes was positively correlated with % body fat (p = 0.03), SAT mass (p = 0.01), VAT mass (p = 0.02), VAT:TAT (p = 0.05), and IHL (p = 0.09; trend). The relative (percent) change in small adipocytes was positively associated with the increase in whole-body fat (p = 0.001), VAT mass (p = 0.0003), VAT:TAT (p = 0.01), and IHL (p = 0.007) in response to overfeeding.

Conclusions

These findings, surprisingly, indicate that during substantial weight gain, an increase in small adipocytes (suggesting hyperplastic expansion) is associated with impaired (not improved) metabolic health outcomes, specifically visceral and ectopic fat accumulation.

Clinical trial registration

ClinicalTrials.gov Identifier- NCT01672632.

This is a preview of subscription content

Access options

Buy article

Get time limited or full article access on ReadCube.

$32.00

All prices are NET prices.

Fig. 1: The % change in small adipocytes was positively associated with the % change in visceral and ectopic fat deposition in response to overfeeding.

Data availability

The data generated and/or analyzed during the study are available from the corresponding author on reasonable request.

References

  1. Virtue S, Vidal-Puig A. Adipose tissue expandability, lipotoxicity and the Metabolic Syndrome–an allostatic perspective. Biochim Biophys Acta. 2010;1801:338–49. Epub 2010/01/09

    CAS  Article  Google Scholar 

  2. Danforth E Jr. Failure of adipocyte differentiation causes type II diabetes mellitus? Nat Genet. 2000;26:13.

    CAS  Article  Google Scholar 

  3. McLaughlin T, Sherman A, Tsao P, Gonzalez O, Yee G, Lamendola C, et al. Enhanced proportion of small adipose cells in insulin-resistant vs insulin-sensitive obese individuals implicates impaired adipogenesis. Diabetologia. 2007;50:1707–15.

    CAS  Article  Google Scholar 

  4. Pasarica M, Xie H, Hymel D, Bray G, Greenway F, Ravussin E, et al. Lower total adipocyte number but no evidence for small adipocyte depletion in patients with type 2 diabetes. Diabetes Care. 2009;32:900–2.

    Article  Google Scholar 

  5. McLaughlin T, Lamendola C, Coghlan N, Liu TC, Lerner K, Sherman A, et al. Subcutaneous adipose cell size and distribution: relationship to insulin resistance and body fat. Obesity. 2014;22:673–80.

    CAS  Article  Google Scholar 

  6. Johannsen DL, Tchoukalova Y, Tam CS, Covington JD, Xie W, Schwarz JM, et al. Effect of 8 weeks of overfeeding on ectopic fat deposition and insulin sensitivity: testing the “adipose tissue expandability” hypothesis. Diabetes Care. 2014;37:2789–97.

    CAS  Article  Google Scholar 

  7. McLaughlin T, Craig C, Liu LF, Perelman D, Allister C, Spielman D, et al. Adipose cell size and regional fat deposition as predictors of metabolic response to overfeeding in insulin-resistant and insulin-sensitive humans. Diabetes. 2016;65:1245–54.

    CAS  Article  Google Scholar 

  8. Weyer C, Foley JE, Bogardus C, Tataranni PA, Pratley RE. Enlarged subcutaneous abdominal adipocyte size, but not obesity itself, predicts type II diabetes independent of insulin resistance. Diabetologia. 2000;43:1498–506.

    CAS  Article  Google Scholar 

  9. Lessard J, Laforest S, Pelletier M, Leboeuf M, Blackburn L, Tchernof A. Low abdominal subcutaneous preadipocyte adipogenesis is associated with visceral obesity, visceral adipocyte hypertrophy, and a dysmetabolic state. Adipocyte. 2014;3:197–205.

    CAS  Article  Google Scholar 

  10. Arner E, Westermark PO, Spalding KL, Britton T, Ryden M, Frisen J, et al. Adipocyte turnover: relevance to human adipose tissue morphology. Diabetes. 2010;59:105–9.

    CAS  Article  Google Scholar 

  11. Hoffstedt J, Arner E, Wahrenberg H, Andersson DP, Qvisth V, Lofgren P, et al. Regional impact of adipose tissue morphology on the metabolic profile in morbid obesity. Diabetologia. 2010;53:2496–503.

    CAS  Article  Google Scholar 

  12. White UA, Fitch MD, Beyl RA, Hellerstein MK, Ravussin E. Association of in vivo adipose tissue cellular kinetics with markers of metabolic health in humans. J Clin Endocrinol Metab. 2017;102:2171–8.

    Article  Google Scholar 

  13. Tam CS, Covington JD, Bajpeyi S, Tchoukalova Y, Burk D, Johannsen DL, et al. Weight gain reveals dramatic increases in skeletal muscle extracellular matrix remodeling. J Clin Endocrinol Metab. 2014;99:1749–57.

    CAS  Article  Google Scholar 

  14. Koska J, Stefan N, Permana PA, Weyer C, Sonoda M, Bogardus C, et al. Increased fat accumulation in liver may link insulin resistance with subcutaneous abdominal adipocyte enlargement, visceral adiposity, and hypoadiponectinemia in obese individuals. Am J Clin Nutr. 2008;87:295–302.

    CAS  Article  Google Scholar 

  15. Korenblat KM, Fabbrini E, Mohammed BS, Klein S. Liver, muscle, and adipose tissue insulin action is directly related to intrahepatic triglyceride content in obese subjects. Gastroenterology. 2008;134:1369–75.

    CAS  Article  Google Scholar 

  16. Bays H. Central obesity as a clinical marker of adiposopathy; increased visceral adiposity as a surrogate marker for global fat dysfunction. Curr Opin Endocrinol Diabetes Obes. 2014;21:345–51.

    CAS  Article  Google Scholar 

  17. Kursawe R, Eszlinger M, Narayan D, Liu T, Bazuine M, Cali AM, et al. Cellularity and adipogenic profile of the abdominal subcutaneous adipose tissue from obese adolescents: association with insulin resistance and hepatic steatosis. Diabetes. 2010;59:2288–96.

    CAS  Article  Google Scholar 

Download references

Acknowledgements

The authors thank Caitlin Hebert (Pennington Biomedical Research Center) for technical assistance.

Funding

This work was supported by National Institute of Diabetes and Digestive and Kidney Diseases grants R03DK112006 (UW) and R01DK060412 and P30DK072476 (ER) through the National Institutes of Health. RAB is supported in part by 1 U54 GM104940 from the National Institute of General Medical Sciences of the National Institutes of Health, which funds the Louisiana Clinical and Translational Science Center.

Author information

Authors and Affiliations

Authors

Contributions

The author contributions are as follows. UW acquired the data, played an important role in interpreting the results, drafted and revised the manuscript, approved the final version, had full access to the data in the study, and agreed to be accountable for all aspects of the work to ensure that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved. RAB acquired and analyzed experimental data, described all statistical methods, revised the manuscript, and approved the final version. ER conceived and designed the work that led to the submission, reviewed the data, played an important role in interpreting the results, revised the manuscript, approved the final version, and agreed to be accountable for all aspects of the work in ensuring the questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved.

Corresponding author

Correspondence to Ursula White.

Ethics declarations

Competing interests

The authors declare no competing interests.

Additional information

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

Supplementary information

Rights and permissions

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

White, U., Beyl, R.A. & Ravussin, E. A higher proportion of small adipocytes is associated with increased visceral and ectopic lipid accumulation during weight gain in response to overfeeding in men. Int J Obes (2022). https://doi.org/10.1038/s41366-022-01150-y

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • DOI: https://doi.org/10.1038/s41366-022-01150-y

Search

Quick links