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 lowerbody 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.adipocyte | body composition | body fat gain | fat distribution | preadipocyte A ccumulation of fat in upper-body/visceral adipose tissue and ectopic sites, including muscle and the liver, is associated with insulin resistance and obesity-related metabolic abnormalities (1), whereas preferential lower-body fat gain seems to have a protective effect (2-4). Thus, the mechanism(s) by which expansion of some depots occurs at the expense of others is of considerable interest. Recently, it has been suggested that fat-cell number remains stable after approximately age 20 y, implying that fat gain during adulthood is the result of adipocyte hypertrophy, not hyperplasia (5). If so, fat gain and body fat distribution would depend entirely on regional fat-cell number before age 20 y and extent of adipocyte hypertrophy. These conclusions, however, were based on measurements of abdominal s.c. fat-cell size (5), but fat-cell progenitors from different body-fat depots have distinct properties (6-8). Thus, we were reluctant to accept the tenet that adults do not develop new adipocytes with weight gain. To test whether different fat-tissue depots vary with respect to cellular mechanisms of fat enlargement, we analyzed different adipose tissue beds in individuals longitudinally.Upper-body and lower-body s.c. fat account for the vast majority of total body fat in normal-weight...

Pathophysiology of Human Visceral Obesity: An Update

“…Lower body fat compartments of obese women contain more adipocytes than those of lean women, whereas obesity is not related to cell number in lower-body compartments of men (560). Consistent with these findings, a longitudinal study performed in men and women showed that adipocyte progenitor cells of the lower body fat compartments can develop rapidly into mature adipocytes in response to overfeeding and that this response depends partially on sex of the participant and baseline adipocyte size (563). These results indirectly suggest that during weight gain, lower-body adipose tissues tend to expand through hyperplasia in women, but through hypertrophy in men (560,563).…”

Adipocyte hypertrophy-hyperplasia balance contributes to weight loss after bariatric surgery

“…6 Decreased preadipocyte frequency and proliferative capacity is associated with obesity and metabolic disease in some, 6,14,[16][17][18] but not all 19 studies. These conflicting literature may result from patient heterogeneity, wide intrinsic variability in human preadipocyte frequency, 19,20 and different techniques used to quantify preadipocytes. One study demonstrated a relationship between decreased preadipocyte number and DM restricted to VAT, 16 similar to our findings and consistent with the well-established stronger association of metabolic disease with VAT.…”

Heterogeneity of adipose tissue in development and metabolic function

“…2), which some studies have shown occurs primarily in the visceral fat depots of mice (Kim et al, 2014;Wang et al, 2013). Other studies have shown an association between hyperplasia and subcutaneous fat depots (Tchkonia et al, 2013), with a higher capacity for adipogenesis observed in femoral rather than in abdominal subcutaneous depots in humans (Tchoukalova et al, 2010). However, a study by van Beek and colleagues demonstrated that pgWAT in mice has a limited capacity to store lipids, which is reached when mice achieve an average body weight of 40 g (van Beek et al, 2015).…”