Lower Body Obese Women Research Articles

Upper-body obese women are resistant to postprandial stimulation of protein synthesis

Upper-body, i.e. visceral, obesity is associated with insulin resistance and impaired protein synthesis. It is unclear whether postprandial stimulation of protein synthesis is affected by body fat distribution. We investigated the postprandial protein anabolic response in a cohort of obese women. Participants were studied after an overnight fast and after a mixed meal, grouped as upper-body obese (UBO, waist-to-hip ratio, WHR, >0.85, n = 6) vs. lower-body obese (LBO, WHR <0.80, n = 7). Lipid and carbohydrate metabolism were assessed by measurements of plasma free fatty acids (FFA), insulin and glucose plasma concentrations, and calculation of the Quicki index from fasting glucose and insulin values. Different labels of stable isotopes of phenylalanine were administered intravenously and orally, and leg and whole-body protein breakdown and synthesis were calculated from phenylalanine/tyrosine isotopic enrichments in femoral arterial and venous blood, using equations for steady-state kinetics. Data are denoted as mean ± SD. Age (38 vs. 40, p = 0.549) and body-mass index (33.7 ± 1.9 vs. 35.0 ± 1.8, p = 0.241) were similar in both groups. UBO subjects had more visceral fat (p = 0.002) and higher fat-free body mass (FFM) (p = 0.015). Plasma insulin concentrations were greater in UBO than LBO women (p = 0.013), and UBO were less insulin sensitive (Quicki = 0.32 ± 0.01 vs. 0.36 ± 0.02, p = 0.005). Protein kinetics across the leg were not different between groups. Fasting whole body protein balance was similarly negative in both groups (UBO -6.5 ± 2.4 vs. LBO -7.6 ± 0.9 μmol/kgFFM/h, p = 1.0). Postprandially, whole body protein balance became less positive in UBO than in LBO (14.8 ± 3.7 vs. 20.2 ± 3.7 μmol/kgFFM/h, p = 0.017). Whole-body protein balance following a meal is less positive in upper-body obese, insulin-resistant, women than in lower-body obese women.

Impact of body composition on very-low-density lipoprotein-triglycerides kinetics

Upper body obese (UBO) subjects have greater cardiovascular disease risk than lower body obese (LBO) or lean subjects. Obesity is also associated with hypertriglyceridemia that may involve greater production and impaired removal of very-low-density lipoprotein (VLDL)-triglycerides (TG). In these studies, we assessed the impact of body composition on basal VLDL-TG production, VLDL-TG oxidation, and VLDL-TG storage. VLDL-TG kinetics were assessed in 10 UBO, 10 LBO, and 10 lean women using a bolus injection of [1-(14)C]VLDL-TG. VLDL-TG oxidation was measured by (14)CO(2) production (hyamine trapping) and VLDL-TG adipose tissue storage by fat biopsies. Insulin sensititvity was assessed by the hyperinsulinemic-euglycemic clamp technique and body composition by dual X-ray absorptiometry in combination with computed tomography. Hepatic VLDL-TG production was significantly greater in UBO than in lean women [(mumol/min) UBO: 64.8 (SD 40.0) vs. LBO: 42.5 (SD 25.6) vs. lean: 31.8 (SD 13.3), P = 0.04], whereas VLDL-TG oxidation was similar in the three groups and averaged 20% of resting energy expenditure [(mumol/min) UBO: 38.3 (SD 26.5) vs. LBO: 23.5 (SD 13.5) vs. lean: 21.1 (SD 9.7), P = 0.09]. In UBO women, more VLDL-TG was deposited in upper body subcutaneous fat [VLDL-TG redeposition in abdominal adipose tissue (mumol/min): UBO: 5.0 (SD 2.9) vs. LBO: 4.0 (SD 3.2) vs. lean: 1.3 (SD 1.0), ANOVA P = 0.01]; in LBO women, more VLDL-TG was deposited in femoral fat [VLDL-TG redeposition in femoral adipose tissue (mumol/min): UBO: 5.1 (SD 3.1) vs. LBO: 5.8 (SD 4.3) vs. lean: 2.3 (SD 1.5), ANOVA P = 0.04]. Only a small proportion of VLDL-TG (8-16%) was partitioned into redeposition in either group. We found that elevated VLDL-TG production without concomitant increased clearance via oxidation and adipose tissue redeposition contributes to hypertriglyceridemia in UBO women.

The influence of sex and obesity phenotype on meal fatty acid metabolism before and after weight loss

Background: Regional differences in meal fat storage may explain the preservation of fat accumulation in obese persons.Objective: The objective was to determine whether meal fatty acid (FA) metabolism differs by sex and obesity phenotypes before and after weight loss.Design: A [3H]triolein-containing meal was given to trace meal FA oxidation (3H2O generation) and adipose tissue uptake (abdominal subcutaneous and gluteal biopsy samples) in 13 upper-body obese (UOb) men, 9 UOb women, and 8 lower-body obese (LOb) women (study 1). Dual-energy X-ray absorptiometry and abdominal computed tomography were used to measure fat distribution. The subjects participated in a diet and exercise weight-loss program, after which 23 subjects returned for an identical study (study 2).Results: In study 1, the storage of meal FA (mg meal fat/g adipose lipid) was greater in gluteal than in abdominal fat (P = 0.022) in LOb women, but not in UOb women or UOb men. UOb men stored a lesser percentage of meal FAs in both upper- and lower-body subcutaneous fat than did the LOb and UOb women (P = 0.001 and P = 0.044, respectively). The participants who returned for study 2 had lost 14.1 ± 1.1 kg. Changes in the uptake of meal FAs followed a pattern indicative of obesity phenotype maintenance by group. The uptake of meal FAs increased in upper-body subcutaneous fat (P = 0.028) in weight-reduced UOb women and UOb men (P = 0.046) and decreased in lower-body fat (P = 0.025) in UOb men.Conclusion: The differences in meal FA trafficking by obesity phenotype suggest that meal FA storage may play a role in regulating body fat distribution in obese persons.

Committed subcutaneous preadipocytes are reduced in human obesity

The aim of this study was to test whether the availability of committed preadipocytes in abdominal and femoral subcutaneous adipose tissue varies with obesity and body fat distribution. Body composition, fat cell size, committed preadipocytes and macrophages were measured in subcutaneous abdominal and femoral adipose depots of 17 lean, 16 upper-body-obese (UBO) and 13 lower-body-obese (LBO) women. Preadipocytes and macrophages were identified by simultaneous staining with the respective markers aP2 and CD68. In a subset of samples we measured preadipocyte proliferation, differentiation and susceptibility to apoptosis. Abdominal adipocytes were smaller in lean than in obese women. Committed preadipocytes represented a greater fraction of stromovascular cells in lean than in obese women but were similar between UBO and LBO women (abdomen: approximately 30 +/- 3 vs approximately 17 +/- 2%; thigh: approximately 30 +/- 3 vs approximately 17 +/- 2%). Preliminary data suggested that preadipocyte kinetics were similar in LBO and lean women, whereas preadipocytes of UBO women differentiated less and were more susceptible to apoptotic stimuli. The fraction of stromovascular cells that were macrophages was greater in both depots in obese women (UBO and LBO) than in normal-weight women, but the difference was not statistically significant. The proportion of subcutaneous adipose tissue stromovascular cells that are committed preadipocytes is reduced with obesity. This could be due to greater recruitment of preadipocytes to adipogenesis or greater preadipocyte apoptosis, depending upon the obesity phenotype. These data are consistent with the concept that body fat distribution may be regulated partly through differences in adipogenesis.

Impaired insulin action in subcutaneous adipocytes from women with visceral obesity.

Visceral obesity is associated with resistance to the antilipolytic effect of insulin in vivo. We investigated whether subcutaneous abdominal and gluteal adipocytes from viscerally obese women exhibit insulin resistance in vitro. Subjects were obese black and white premenopausal nondiabetic women matched for visceral adipose tissue (VAT), total adiposity, and age. Independently of race and adipocyte size, increased VAT was associated with decreased sensitivity to insulin's antilipolytic effect in subcutaneous abdominal and gluteal adipocytes. Absolute lipolytic rates at physiologically relevant concentrations of insulin or the adenosine receptor agonist N(6)-(phenylisopropyl)adenosine were higher in subjects with the highest vs. lowest VAT area. Independently of cell size, abdominal adipocytes were less sensitive to the antilipolytic effect of insulin than gluteal adipocytes, which may partly explain increased nonesterified fatty acid fluxes in upper vs. lower body obese women. Moreover, increased VAT was associated with decreased responsiveness, but not decreased sensitivity, to insulin's stimulatory effect on glucose transport in abdominal adipocytes. These data suggest that insulin resistance of subcutaneous abdominal and, to a lesser extent, gluteal adipocytes may contribute to increased systemic lipolysis in both black and white viscerally obese women.

Regional postprandial fatty acid metabolism in different obesity phenotypes.

To examine if postprandial splanchnic/hepatic free fatty acid (FFA) delivery is increased in upper-body (UB) obesity, and to determine the adipose tissue depots responsible for the greater postprandial FFA availability, we measured systemic and regional uptake and release of FFAs ([1-(14)C]palmitate) before and during a 5-h frequent-feeding mixed meal in eight UB and eight lower-body (LB) obese women. Postabsorptive FFA flux and splanchnic FFA delivery were not different in UB and LB obese women; however, postprandial FFA concentrations (257 +/- 45 vs. 81 +/- 12 micromol/l, P < 0.0001), FFA flux (8.5 +/- 1.2 vs. 3.9 +/- 0.8 micromol x kg(-1) fat-free mass x min(-1), P < 0.0001), splanchnic FFA delivery (275 +/- 45 vs. 88 +/- 24 micromol/min, respectively, P < 0.005), and estimated hepatic FFA delivery were greater in UB than LB obese women. Nonsplanchnic UB adipose tissue FFA release was greater in UB than in LB obese women (276 +/- 71 vs. 97 +/- 37 micromol/min, respectively, P < 0.05) and accounted for the greater postprandial FFA availability in UB obesity. Postprandial leg glucose uptake was less in UB than in LB obese women (8.4 +/- 5.1 vs. 22.9 +/- 2.6 micromol x kg(-1) leg fat-free mass x min(-1), P < 0.05). We conclude that the elevated postprandial FFA release observed in UB obese women originates from the nonsplanchnic UB fat, not visceral fat. These results suggest that visceral fat may be a marker for, but not the source of, excess postprandial FFAs in obesity.

Circadian rhythm of plasma leptin levels in upper and lower body obese women: influence of body fat distribution and weight loss.

Plasma leptin concentrations were measured every 20 min for 24 h in eight normal weight women and in eight upper body and eight lower body obese women matched for body mass index. The circadian rhythm of leptin, which could mathematically be described by a cosine, was characterized by an acrophase just after midnight in all subjects. The amplitude of a cosine fit as well as the average 24-h leptin concentration were increased by 280% and 420%, respectively, in obese compared to normal weight women. All characteristics of leptin concentration profiles were similar in upper body and lower body obese women, except for a significantly higher amplitude in the lower body obese group. Visceral and sc body fat depots were measured using magnetic resonance imaging in all three groups. Average 24-h leptin concentrations were strongly correlated with sc fat (r = 0.84), whereas visceral fat was not an independent predictor of the plasma leptin level. A loss of 50% of the overweight was associated with a 55% decrease in the average 24-h leptin concentrations in obese women (95% confidence interval, 12.3, 26.6), whereas the characteristics of the circadian rhythm of leptin remained unchanged. Finally, it was observed that a fasting plasma leptin concentration is not an acceptable indicator of the average leptin concentration over 24 h.

OBESITY SUPPRESSES THE GH RESPONSE TO EXERCISE

278 Resting serum GH concentrations are decreased in obesity. Exercise increases GH levels in non-obese (NonOb) individuals; however, it is unknown if the GH response to exercise is lower in obese compared to NonOb individuals. To examine this we studied 8 NonOb, 11 lower body obese (LBO) and 12 upper body obese (UBO) women. The impact of 16 wks of aerobic exercise training on the GH response to exercise was also examined in a subset of obese women (LBO & UBO combined). Blood samples (0700-1300 h) were taken every 5 min 1 h before, during and 4.5 h following 30 min of treadmill walking (70% VO2 max). GH levels were measured with a sensitive (0.002 μg/L) chemiluminescence assay TableTableAfter 16 wks of aerobic training, no change was observed in the GH response to exercise in the obese women (n=10; pre 379±144 vs post 350±55 min·μg/L). In summary, the GH response to exercise was greater in NonOb than obese women and the response tended to be lower in UBO than LBO women. Short term aerobic training improved fitness but did not increase the GH response. Obesity suppresses the GH response to exercise compared to NonOb women.

Circadian Rhythm of Plasma Leptin Levels in Upper and Lower Body Obese Women: Influence of Body Fat Distribution and Weight Loss

Circadian Rhythm of Plasma Leptin Levels in Upper and Lower Body Obese Women: Influence of Body Fat Distribution and Weight Loss

The differential effects of body fat distribution on insulin and glucose metabolism during pregnancy

Objective: Our purpose was to investigate whether maternal obesity, or more specifically body fat distribution, is associated with alterations in carbohydrate metabolism during pregnancy.Study Design: A longitudal study of oral glucose tolerance tests, insulin, C peptide, and glucagon levels during each trimester and post partum was undertaken in nine lean and 14 obese women. Obese women were divided into lower body obese (n = 6, waist/hip ratio < 0.9) and upper body obese (n = 8, waist/hip ratio ≥0.9).Results: Fasting blood glucose levels declined with advancing gestation only in lean subjects. Upper body obese women demonstrated maximal glucose response and insulin area under the curve by the second trimester, whereas lean and lower body obese women did not until the third trimester. Insulin areas were significantly elevated in upper body obese compared with lower body obese women (second trimester, p < 0.01; third trimester, p < 0.03; post partum p < 0.05). In contrast, C peptide levels were similar in obese subgroups and were significantly elevated only when compared with those of lean women. C peptide/insulin molar ratios were lower in upper body obese women during the second trimester (4.3 ± 0.8) and third trimester (4.2 ± 0.7) compared with lean (6.5 ± 1.3, 6.7 ± 0.5) and lower body obese women (7.9 ± 1.4, 6.5 ± 1.4) (p < 0.01). A significant relationship between waist/hip ratio and glucose level (r = 0.70, p < 0.004) and insulin areas (r = 0.76, p < 0.001) was present in late pregnancy in obese subjects.Conclusions: Relative hyperinsulinemia and earlier maximal glucose response in upper body obese women suggests that body fat distribution may explain the metabolic heterogeneity present in obese women during pregnancy. Body fat topography may serve as a potential marker for the early development of carbohydrate intolerance during pregnancy.

Postprandial Free Fatty Acid Kinetics Are Abnormal in Upper Body Obesity

Excess free fatty acid release (rate of appearance) is seen in overnight postabsorptive, upper body obese women and, if present postprandially, could contribute to glucose intolerance. These studies examine the antilipolytic effect of a mixed meal in upper body obese, lower body obese, and nonobese women and the contribution of meal triglyceride fatty acids to circulating free fatty acids. Eight upper body obese, 8 lower body obese, and 8 nonobese age-matched, premenopausal women were studied. Systemic oleate Ra ([3H]oleate) was measured before and after an evening meal that contained triolein labeled with [14C]triolein as the only source of fat. Premeal oleate Ra was greater in both upper body obese and lower body obese women than nonobese women. The nadir of total oleate Ra occurred 90-240 min postprandially and was less (P < 0.01) in nonobese and lower body obese women (63 +/- 10 and 87 +/- 17 mumol/min) than in upper body obese women (140 +/- 21 mumol/min). Meal oleate Ra contributed substantially to total oleate Ra. The nadir for endogenous oleate Ra in nonobese and lower body obese women was less (P < 0.01) than that observed in upper body obese women. We conclude that the antilipolytic effect of a mixed meal is reduced in upper body obese women and that meal triglyceride fatty acids contribute significantly to postprandial free fatty acid flux.

Differential effects of body fatness and body fat distribution on risk factor for cardiovascular disease in women. Impact of weight loss.

This study examines the role of obesity and body fat distribution (ie, waist-to-hip ratio [WHR]) on cardiovascular disease (CVD) risk factors in 50 nondiabetic, obese (body mass index [BMI], 31 +/- 2 kg/m2, mean +/- SD), 45 +/- 10-year-old women. The data obtained at baseline and after weight loss were analyzed after dividing subjects by WHR into upper-body (WHR > 0.80) and lower-body (WHR < or = 0.80) groups and by median-split BMI into more obese (BMI > or = 31) and less obese (BMI < 31) groups. At baseline, the upper-body obese women, when compared with lower-body obese women, had higher plasma triglycerides (TGs) (175 +/- 85 versus 111 +/- 47 mg/dL, respectively; P < .001) and lower high-density lipoprotein cholesterol (HDL-C) (44 +/- 10 versus 54 +/- 11, respectively; P < .01) but similar total and low-density lipoprotein cholesterol levels and blood pressure. There were no significant differences in these CVD risk factors at baseline by BMI split. Although weight loss (-9 +/- 5 kg) lowered blood pressure and TGs irrespective of WHR or BMI, only upper-body obese women raised HDL-C. Moreover, the magnitude of the changes was greatest in women with an upper-body fat distribution. In women with WHR > 0.80, HDL-C increased by 11%, to 49 mg/dL (P < .001), and TGs decreased by 24%, to 134 mg/dL (P < .001).(ABSTRACT TRUNCATED AT 250 WORDS)

Differential health benefits of weight loss in upper-body and lower-body obese women

Upper-body obesity (UB Ob) is more strongly associated with adverse health consequences; however, few obesity-treatment studies have examined outcome according to body-fat distribution. To examine whether diet and formal- or informal-exercise instruction causes differential changes in health and lipid profiles, ten LB Ob and nine UB Ob premenopausal women received dietary intervention (2.1 MJ-deficit/d for 16 wk) and were randomly assigned to either formal- or informal-exercise instruction. Weight loss was similar between groups (approximately 8 kg), and no change occurred in lean body mass or basal metabolic rate. Baseline cholesterol and triglycerides were greater (P < 0.01) in UB Ob than LB Ob women and decreased more (P < 0.01) in response to treatment in UB Ob women. Formal exercise instruction increased high-density-lipoprotein cholesterol (P < 0.05) especially in UB Ob women. Future studies on treatment of obesity should include consideration of regional fat distribution.

Regulation of forearm lipolysis in different types of obesity. In vivo evidence for adipocyte heterogeneity.

Forearm and systemic adipose tissue free fatty acid (FFA) release was measured in eight nonobese, six lower-body obese, and eight upper-body obese women under basal, hyperinsulinemic, and hypoinsulinemic conditions to determine whether forearm fat is regulated in a similar manner as whole body fat. Adipose tissue palmitate release was greater from forearm than whole body (5.97 +/- 0.75 vs. 3.84 +/- 0.34 mumol.kg fat-1.min-1, respectively, P less than 0.005, n = 22 subjects). Systemic palmitate release, relative to fat mass, was significantly (P less than 0.01) greater in nonobese than upper-body obese, and upper-body obese than lower-body obese women, and forearm adipose tissue palmitate release followed the same pattern. Hyperinsulinemia suppressed systemic and forearm lipolysis to similar degrees, however, hypoinsulinemia consistently increased systemic palmitate flux without increasing forearm palmitate release. These results confirm the heterogeneity of adipose tissue in an in vivo model and emphasize the need to consider which adipose tissue depots are responsible for the differences in systemic FFA flux in obese and nonobese humans.

Glucose metabolism in obesity: influence of body fat distribution.

The dose-response relationships between portal venous insulin concentrations and hepatic glucose production and between peripheral insulin concentrations and peripheral glucose utilization were determined in 8 nonobese and 17 obese premenopausal women with either upper or lower body fat localization. The glucose production dose-response curves for the two obese groups were shifted to the right at all levels of portal insulinemia. The upper body obese women had a greater rightward shift compared to the lower body obese women. The peripheral glucose utilization dose-response curve was shifted to the right in the lower body obese women, but maximal glucose utilization was normal. The upper body obese women had both a greater rightward shift and a marked reduction in maximal glucose utilization. The insulin concentrations that had half-maximal effects on glucose production and utilization were similar in each group. These results indicate that the liver is not inherently more sensitive to insulin than peripheral tissues. Obesity is associated with a moderate diminution of hepatic and peripheral insulin sensitivity. Upper body fat localization in obese women is characterized by a greater diminution in insulin sensitivity and decline in peripheral insulin responsivity than is lower body fat localization. The marked peripheral insulin resistance in the former group may account for the increased prevalence of glucose intolerance.