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

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/m 2 ) 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.