Regional differences in cellular mechanisms of adipose tissue gain with overfeeding

Abstract

Body fat distribution is an important predictor of the metabolic consequences of obesity, but the cellular mechanisms regulating regional fat accumulation are unknown. We assessed the changes in adipocyte size (photomicrographs) and number in response to overfeeding in upper- and lower-body s.c. fat depots of 28 healthy, normal weight adults (15 men) age 29 ± 2 y. We analyzed how these changes relate to regional fat gain (dual energy X-ray absorptiometry and computed tomography) and baseline preadipocyte proliferation, differentiation [peroxisome proliferator-activated receptor-γ2 (PPARγ2) and CCAAT/enhancer binding protein-α (C/EBPα) mRNA]), and apoptotic response to TNF-α. Fat mass increased by 1.9 ± 0.2 kg in the upper body and 1.6 ± 0.1 kg in the lower body. Average abdominal s.c. adipocyte size increased by 0.16 ± 0.06 μg lipid per cell and correlated with relative upper-body fat gain (r = 0.74, P < 0.0001). However, lower-body fat responded to overfeeding by fat-cell hyperplasia, with adipocyte number increasing by 2.6 ± 0.9 × 10(9) cells (P < 0.01). We found no depot-differences in preadipocyte replication or apoptosis that would explain lower-body adipocyte hyperplasia and abdominal s.c. adipocyte hypertrophy. However, baseline PPARγ2 and C/EBPα mRNA were higher in abdominal than femoral s.c. preadipocytes (P < 0.005 and P < 0.03, respectively), consistent with the ability of abdominal s.c. adipocytes to achieve a larger size. Inherent differences in preadipocyte cell dynamics may contribute to the distinct responses of different fat depots to overfeeding, and fat-cell number increases in certain depots in adults after only 8 wk of increased food intake.

Fig. 1.

Relationship between baseline mature adipocyte cell size (x axis) and change in adipocyte size (y axis) in response to weight gain. •, data from women; □, data from men. (A) Abdominal s.c. adipocytes vs. change in abdominal adipocyte size. The relationship is significant for women (r = −0.64, P = 0.02) but not for men (r = 0.23, P = 0.43). (B) Femoral adipocytes vs. change in femoral adipocyte size. The relationship is significant for women (r = −0.64, P = 0.02) and is of borderline significance for men (r = −0.52, P = 0.057).

Fig. 2.

Relationships between changes in regional s.c. fat gain and changes in adipocyte size. •, data from women; □, data from men. (A) Relative change (%) in upper-body fat mass {[(upper-body fat mass postoverfeeding − upper-body fat mass at baseline) ÷ upper-body fat mass at baseline] × 100} vs. relative change (%) in abdominal s.c. adipocyte size {[(fat-cell size postoverfeeding − fat-cell size at baseline) ÷ fat-cell size at baseline] × 100}. (B) Change in abdominal s.c. fat-cell size vs. the relative amount of lower-body fat gain {[(lower-body fat mass postoverfeeding − lower-body fat mass at baseline) ÷ lower-body fat mass at baseline] × 100}. Because the data were not normally distributed, regression analysis was performed using logarithmically transformed values of the relative increase in lower-body fat gain. The r and P values provided are from linear regression analysis of the transformed data; the depicted regression line is best fit using a power function.