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...

Abdominal adipocyte size is related to body fat distribution. Adipocyte size in a person seems to be globally regulated by factors independent of variations in body fat distribution.

1OBJECTIVE-Obesity and diabetes are characterized by the incapacity to use fat as fuel. We hypothesized that this reduced fat oxidation is secondary to a sedentary lifestyle. RESEARCH DESIGN AND METHODS-We investigated the effect of a 2-month bed rest on the dietary oleate and palmitate trafficking in lean women (control group, n ϭ 8) and the effect of concomitant resistance/aerobic exercise training as a countermeasure (exercise group, n ϭ 8). Trafficking of stable isotope-labeled dietary fats was combined with muscle gene expression and magnetic resonance imaging-derived muscle fat content analyses. 31 ]palmitate oxidation by Ϫ8.2 Ϯ 4.9% (P Ͻ 0.0001). Despite a decreased spontaneous energy intake and a reduction of 1.9 Ϯ 0.3 kg (P ϭ 0.001) in fat mass, exercise training did not mitigate these alterations but partially maintained fat-free mass, insulin sensitivity, and total lipid oxidation in fasting and fed states. In both groups, muscle fat content increased by 2.7% after bed rest and negatively correlated with the reduction in [d 31 ]palmitate oxidation (r 2 ϭ 0.48, P ϭ 0.003). I n our search of the environmental factors that fuelled the pandemic of obesity, we face a paradox. Although sedentary lifestyle has been highlighted for decades as one of the main factors triggering weight gain, the physiology of physical inactivity has received little attention (1). Clearly, the causal relationships between sedentary behaviors and obesity are essentially based on epidemiological studies or on the indirect beneficial effects of exercise training (2). None of these studies provide evidence to support a cause-and-effect relationship. RESULTS-In CONCLUSIONS-WhileObesity is a fat storage disease characterized by insulin resistance and a decreased capacity to oxidize lipids (3) in fasting (4) and postprandial (5) conditions. Because weight reduction was not associated with improvement in fat utilization (6), it was suggested as a primary impairment in the etiology of obesity, rather than an adaptive response. Consequently, the delineation of the causes responsible for this reduced capacity to oxidize fat appears to be a fundamental prerequisite to develop efficient strategies against obesity.We previously extended the early Mayer hypothesis (7) and hypothesized that the decreased fat oxidation observed in obese and postobese subjects is due to the generalized adoption of sedentary behaviors (8). Using strict bed rest as a model, we showed that physical inactivity, per se (i.e., independent of the known physical inactivity-induced energy balance changes), lowers fasting and postprandial fat oxidation (9). Unexpectedly, whereas monounsaturated dietary fat (oleate) oxidation remained unaffected by bed rest, saturated fat (palmitate) oxidation decreased by 11% (9). These results are interesting when considering the north/south gradient in obesity prevalence in France that was not associated with the overall energy intake but in the greater amount of saturated fat in the diet (10).The main objective of our present study wa...

OBJECTIVE Obesity is associated with decreased activity in the prefrontal cortex. Transcranial direct current stimulation (tDCS) modifies cortical excitability and may facilitate improved control of eating. We measured energy intake (EI) and body weight in subjects who received cathodal vs. sham (study 1) and subsequent anodal vs. sham (study 2) tDCS aimed at the left dorsolateral prefrontal cortex (LDLPFC). METHODS Nine (3m,6f) healthy volunteers with obesity (94±15kg [M±SD]; 42±8y) were admitted as inpatients for 9d to participate in a single-blind, randomized, placebo-controlled crossover experiment. Study 1: following 5d of a weight-maintaining diet, participants received cathodal or sham tDCS (2mA, 40min) on 3 consecutive mornings and then ate ad libitum from a computerized vending machine, which recorded EI. Weight was measured daily. Study 2: participants repeated the study, maintaining original assignment to active (this time anodal) and sham. RESULTS Participants tended to consume fewer kcal/d (p=0.07), significantly fewer kcal from soda (p=0.02) and fat (p=0.03) and had a greater %weight loss (p=0.009) during anodal v. cathodal tDCS. CONCLUSIONS These results indicate a role for the LDLPFC in obesity and food intake. This proof of concept study suggests, for the first time, the potential application of anodal tDCS to facilitate weight loss.