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.
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.
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.
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
Subscribe to Journal
Get full journal access for 1 year
only $9.92 per issue
All prices are NET prices.
VAT will be added later in the checkout.
Tax calculation will be finalised during checkout.
Get time limited or full article access on ReadCube.
All prices are NET prices.
The data generated and/or analyzed during the study are available from the corresponding author on reasonable request.
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
Danforth E Jr. Failure of adipocyte differentiation causes type II diabetes mellitus? Nat Genet. 2000;26:13.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
The authors thank Caitlin Hebert (Pennington Biomedical Research Center) for technical assistance.
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.
The authors declare no competing interests.
Publisher’s note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
About this article
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