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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



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 Identifier- NCT01672632.

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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.


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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.

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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.

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Correspondence to Ursula White.

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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).

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