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1 From the University of Alabama at Birmingham, Departments of Nutrition Sciences (BAG, RLW, and JMJ) and Human Studies (GRH), the Clinical Nutrition Research Center, and the Comprehensive Cancer Center (RD), Birmingham, AL.
2 Supported by grant R01 DK 49779 (to RLW), grant R01 DK 58278 (to BAG), Public Health Service research grant M01-RR00032 from the National Center for Research Resources, and Clinical Nutrition Research Unit grant P30-DK56336. Stouffer’s Lean Cuisine entrées were provided by the Nestlé Food Co, Solon, OH. 3 Address reprint requests to BA Gower, University of Alabama at Birmingham, Department of Nutrition Sciences, Division of Physiology and Metabolism, 427 Webb Building, 1675 University Boulevard, Birmingham, AL 35294-3360. E-mail: bgower{at}uab.edu.
ABSTRACT
Background: Few studies have tested the hypothesis that changes in disease risk factors are more closely associated with changes in visceral fat than with changes in other adipose tissue depots, particularly in subjects with different ethnic or racial backgrounds.
Objective: We describe changes in triacylglycerol, total cholesterol, HDL cholesterol, LDL cholesterol, insulin sensitivity (Si), visceral fat, and subcutaneous abdominal adipose tissue (SAAT) with weight loss in premenopausal, overweight [body mass index (in kg/m2): 27–30], African American (n = 19) and white (n = 18) women.
Design: Assessments were performed before and after diet-induced weight loss to a BMI < 25. Body composition and body fat distribution were assessed with dual-energy X-ray absorptiometry and computed tomography, respectively; Si was assessed with an intravenous-glucose-tolerance test and minimal modeling.
Results: White women lost significantly more visceral fat and less SAAT than did African American women despite similar weight losses (13 kg). Mixed-model analysis indicated significant effects of time (ie, weight loss) on Si, triacylglycerol, HDL cholesterol, and LDL cholesterol and of race on triacylglycerol. Time x race interaction terms were not significant. After adjustment for either total body or visceral fat, time was not related to any outcome variable; however, race remained significantly related to triacylglycerol.
Conclusions: With weight loss, moderately overweight African American and white women experienced significant improvements in Si and lipids. The beneficial effects of weight loss did not differ with race and could not be attributed to a specific body fat depot. Lower triacylglycerol concentrations among African American women are independent of both obesity status and body fat distribution.
Key Words: Body fat distribution • intraabdominal fat • weight loss • insulin sensitivity • cholesterol • triacylglycerol • African American women • white women
INTRODUCTION
It is widely assumed that obesity-related risk factors for cardiovascular disease and type 2 diabetes, such as dyslipidemia and insulin resistance, are primarily associated with the accumulation of visceral fat (1, 2). Thus, one would predict that, with weight loss, overweight persons would show improvements in triacylglycerol concentration, HDL-cholesterol concentration, and insulin resistance that would correspond more closely with the loss of visceral fat than with the loss of adipose tissue from other areas. However, little research has been done, particularly in healthy subjects, to identify the specific adipose tissue depot most closely associated with changes in risk factors resulting from weight loss or to determine whether changes in this depot differ with sex, race, age, or other variables.
Among obese sedentary men and premenopausal women [mean body mass index (BMI; in kg/m2):
The present study was conducted in healthy, overweight (BMI: 27–30), premenopausal African American and white women. The objective was to describe changes in triacylglycerol, total cholesterol, HDL cholesterol, LDL cholesterol, Si, visceral fat, and SAAT with weight loss and to determine whether these changes differed with ethnic-racial group.
SUBJECTS AND METHODS
Subjects
Subjects were 37 premenopausal women aged 21–46 y, 18 white and 19 African American, recruited through newspaper advertisement for a weight-loss study. Study inclusion requirements included a BMI between 27 and 30, a family history of obesity in at least one first-degree relative, normal glucose tolerance (9), a sedentary lifestyle, and a history of regular menstrual cycles. None of the women were taking oral contraceptives or other medications that could affect the outcomes. Ethnicity-race was self-defined; both parents and both sets of grandparents were required to be of the same ethnic-racial group as the subject. The study protocol was approved by the Institutional Review Board for Human Use at the University of Alabama at Birmingham (UAB), and all subjects signed an informed consent form before testing.
Protocol
Before testing in both the overweight and normal-weight states, subjects were maintained in a weight-maintenance state for 4 wk. During the final 2 wk, meals were provided through the General Clinical Research Center (GCRC) at UAB to ensure weight stability of <1% variation and to maintain daily macronutrient intake in the range of 20–23% fat, 16–23% protein, and 55–64% carbohydrate. Subjects were then admitted as inpatients to the GCRC for 4 d, during the follicular phase of the menstrual cycle. All metabolic testing took place during this inpatient period. At discharge, subjects began the weight-loss phase of the study. During this phase, they were provided food by the GCRC that provided 800 kcal (3347 kJ)/d. They were instructed to consume only the food provided by the GCRC. Body weight was monitored twice weekly at the GCRC until the subjects lost >10 kg and reached a target normal or ideal weight (BMI < 25).
Body composition and fat distribution
Body composition (fat mass and lean body mass) was measured by dual-energy X-ray absorptiometry with a Lunar DPX-L densitometer (LUNAR Radiation Corp, Madison, WI) in the Department of Nutrition Sciences at UAB. Subjects were scanned in light clothing while lying flat on their backs with their arms at their sides. Dual-energy X-ray absorptiometry scans were performed and analyzed with adult software version 1.5g. Visceral (intraabdominal) adipose tissue and SAAT were analyzed in the Department of Radiology by computed tomography scanning with a HiLight/Advantage Scanner (General Electric, Milwaukee) as previously described (10). A 5-mm abdominal scan was taken at the level of the umbilicus (approximately the L4-L5 intervertebral space). Scans were later analyzed for cross-sectional area (cm2) of adipose tissue by using the density contour program with Hounsfield units for adipose tissue set at -190 to -30. We have shown the test-retest reliability for visceral fat to be 1.7% (11). All scans were analyzed by the same investigator.
Collection of sera and tolbutamide-modified, frequently sampled, intravenous-glucose-tolerance test
At 0700 after the subjects had fasted for 12 h, flexible intravenous catheters were placed in the antecubital spaces of both of the subjects’ arms. Three blood samples were drawn over a 40-min period, and the sera were subsequently separated and pooled for analysis of lipids. Three additional blood samples were taken over a 20-min period for determination of basal glucose and insulin (the average of the values was used for basal fasting concentrations). At time 0, glucose (50% dextrose; 11.4 g/m2) was administered intravenously. Blood samples (2.0 mL) were then collected at the following times (min) relative to glucose administration at 0 min: 2, 3, 4, 5, 6, 8, 10, 12, 14, 16, 19, 22, 23, 24, 25, 27, 30, 35, 40, 50, 60, 70, 80, 90, 100, 120, 140, 160, and 180. Tolbutamide (125 mg/m2) was injected intravenously at 20 min. Serum samples were analyzed for glucose and insulin, and values were entered into the MINMOD computer program (version 3.0; Richard N Bergman, Department of Physiology and Biophysics, University of Southern California, Los Angeles) for determination of Si and the acute insulin response to glucose (AIRg) (12–14). AIRg is the integrated incremental area under the curve for insulin during the first 10 min of the test.
Assay of glucose, insulin, and lipids
Glucose was measured in 10 µL serum by using an Ektachem DT II System (Johnson and Johnson Clinical Diagnostics, Rochester, NY). In our laboratory, this analysis has a mean intraassay CV of 0.61% and a mean interassay CV of 1.45%. Insulin was assayed in duplicate 200-µL aliquots with Diagnostic Products Corporation (Los Angeles) Coat-A-Count kits. According to the supplier, the cross-reactivity of this assay with proinsulin is 40% at mid-curve; C-peptide is not detected. In our laboratory, this assay has a sensitivity of 11.4 pmol/L (1.9 µIU/mL), a mean intraassay CV of 5%, and a mean interassay CV of 6%. Commercial quality-control serum samples of low, medium, and high insulin concentration (Lyphochek; Bio-Rad, Anaheim, CA) were included in every assay to monitor variation over time. Total cholesterol, HDL cholesterol, and triacylglycerol were measured with the Ektachem DT II System. With this system, HDL cholesterol is measured after the precipitation of LDL and VLDL cholesterol with dextran sulfate and magnesium chloride. Control serum samples of low and high substrate concentration were analyzed with each group of samples, and values for these controls were required to fall within accepted ranges before the samples were analyzed. The DT II is calibrated every 6 mo with reagents supplied by the manufacturer. LDL cholesterol was estimated by using the Friedewald formula (15).
Statistics
For all analyses, values for body-composition variables and serum analytes were log transformed for normality. Analysis of variance was used to test for between-group differences in body composition at baseline and after weight loss and for between-group differences in the change value. A mixed model was used to examine the effect of race, time (weight loss), and the interaction of race and time on the risk factors. For each risk factor, 3 models were generated: 1) unadjusted, 2) adjusted for total body fat, and 3) adjusted for visceral fat. Analysis of variance or covariance, as appropriate, was performed at each time period to generate unadjusted or adjusted means, respectively. All analyses were performed with SAS (version 6.12; SAS Institute Inc, Cary, NC). P values <0.05 were deemed statistically significant.
RESULTS
At baseline, the white and African American groups did not differ significantly with respect to age, BMI, body weight, total fat mass, or total lean body mass, but the white women had significantly more visceral fat (Table 1). Both groups lost 11 kg of total fat mass during the intervention period. However, the African American women lost significantly more SAAT and less visceral fat than did the white women. The difference between groups in the amount of visceral fat lost, but not that of SAAT loss, disappeared when the data were adjusted for baseline values.
View this table:
TABLE 1 . Descriptive characteristics of the study women at baseline and after weight loss1
Mixed-model analysis indicated significant effects of time (weight loss) on Si, triacylglycerol, HDL cholesterol, and LDL cholesterol, and of race on triacylglycerol (lower in African Americans; Table 2). None of the interaction terms (time x race) were significant. After adjustment for either total body fat or visceral fat, time was no longer significantly related to any outcome variable; however, race remained significantly related to triacylglycerol, such that concentrations were significantly lower in African American women, regardless of the means of adjustment. The interaction terms were likewise not significant in the models with adjustment for total fat or visceral fat, indicating that changes in Si, triacylglycerol, total cholesterol, HDL cholesterol, and LDL cholesterol with weight loss did not differ with ethnicity-race, regardless of the means of statistical adjustment. Because white and African American women differed in baseline visceral fat, we also conducted the mixed models with baseline visceral fat as an independent variable. In these models, baseline visceral fat neither made an independent contribution to the models (the relation with triacylglycerol had a P value of 0.085) nor changed the outcome in any way.
View this table:
TABLE 2 . Influence of ethnicity-race on risk factors in the study women before and after weight loss1
Fasting insulin concentrations decreased significantly with weight loss in both groups of women (from 54 ± 5 to 43 ± 3 pmol/L in African American women and from 66 ± 5 to 45 ± 4 pmol/L in white women), as did the AIRg (from 3858 ± 630 to 3132 ± 546 pmol/L x 10 min in African American and from 3042 ± 498 to 2100 ± 378 pmol/L x 10 min in white women).
DISCUSSION
We designed this study to determine whether changes in the metabolic risk factor profile with weight loss differed in premenopausal white and African American women. We hypothesized that white women, who show a greater absolute and relative (8) loss of visceral fat, would also show a greater improvement in the risk factor profile.
Our results indicated that weight loss was associated with improvements in Si, triacylglycerol, HDL cholesterol, and LDL cholesterol in both African American and white women. The beneficial effects of weight loss did not differ by race. Furthermore, statistical adjustment for total fat and visceral fat indicated that the beneficial effects of weight loss could not be attributed to a specific body fat depot. Thus, although white women lost significantly more visceral fat, and less SAAT, than did African American women, the improvement in the metabolic profile was similar. The small amount of visceral fat present in premenopausal women, in an absolute or relative sense (relative to the larger amount of total or subcutaneous fat), may account for the lack of an independent effect of this depot on metabolic risk factors. Although these women were overweight at baseline, the absolute amount of visceral fat among white women was, on average, only slightly above the amount associated with elevated metabolic risk factors in women (110 cm2; 16); that for African American women was, on average, below this amount. Thus, the improvement in risk factors with weight loss may have been due more to the loss of total or subcutaneous fat than to the loss of visceral fat.
To our knowledge, only one other study has assessed both changes in disease risk factors and changes in body fat distribution during weight loss in African American and white women. In a group of 18 obese women (BMI > 30), moderate weight loss (17 kg) produced similar relative changes in visceral fat and SAAT in both African Americans and whites; metabolic risk factors did not change with weight loss in either group (17). These results differ from ours, which indicated that both groups benefited from weight loss. The differences between the studies may be due to a larger sample size and to subject attainment of an ideal body weight (BMI < 25) after weight loss in the present study.
Few studies have examined associations among body fat distribution and metabolic risk factors in healthy, premenopausal white and African American women. One cross-sectional study reported that, among obese premenopausal women (average BMI of 36), the relations of Si and lipids with total and regional (visceral adipose tissue and SAAT) fat were not different in African Americans and whites (18). Similarly, among premenopausal women with a broad range of body fat (average BMI of 30), visceral fat was correlated with Si, fasting insulin, and glucose effectiveness in both African Americans and whites (19). However, SAAT was correlated with Si and fasting insulin only among African Americans; whether this was due to the relatively greater accumulation of SAAT compared with visceral fat among African Americans is not clear.
In a third cross-sectional study involving premenopausal African American and white women with BMIs > 27.3, triacylglycerol, HDL cholesterol, and fasting insulin were predicted by visceral fat and the interaction of visceral fat and race, but not by race alone (20). In addition, although among all subjects triacylglycerol concentrations were higher in white than in African American women, subgroups of African American and white women matched for visceral fat did not differ with respect to triacylglycerol, suggesting that the higher triacylglycerol concentrations in the white women were due solely to greater visceral fat. The significant interaction terms reflected stronger relations between visceral fat and risk factors in white than in African American women.
Our data do not support the hypothesis that greater visceral fat in white women is entirely responsible for higher triacylglycerol. In our study, white women had higher triacylglycerol concentrations than did African American women both before and after adjustment for either visceral fat or total body fat. Thus, it is possible that ethnicity-race has an effect on triacylglycerol independent of both obesity status and body fat distribution. Observations of a more favorable lipid profile in African Americans than in whites have been reported in several studies (18, 21, 22).
In the present study, African American and white women did not differ significantly with respect to Si, regardless of obesity status. This result is similar to that of Albu et al (18), who also did not observe an ethnic-racial difference in Si among obese premenopausal women, but differs from that of numerous other studies that reported lower Si among African Americans than among whites (19, 23–26). Thus, the absence of an ethnic-racial difference in Si was unexpected. Of note, both studies that reported no ethnic difference in Si included only premenopausal women who were overweight (present study) or obese (18). One could speculate that, before menopause, women are protected against insulin resistance as a result of the beneficial effects of estrogen on Si (27). Thus, there may be a lower limit to which Si will fall, regardless of body composition, in women with normal reproductive function.
One limitation of this study was the homogeneous nature of the subject population and the correspondingly low variability in adipose tissue lost from any region. Because of the study design, we were unable to examine correlations between loss of total and regional adipose tissue and changes in risk factors.
In conclusion, after diet-induced weight loss, overweight white women lost more visceral fat than did African American women of similar BMI and with a similar loss of total fat mass. Weight loss resulted in significant improvements in Si and lipids that did not differ by race and that could not be attributed to a specific body fat depot. African American women had more favorable triacylglycerol concentrations than did white women, in both the overweight and normal-weight states, a difference that appeared to be independent of both total and visceral fat mass.
ACKNOWLEDGMENTS
We acknowledge the contributions of study coordinator Paul Zuckerman, research dietician Betty Darnell, and the staff of the General Clinical Research Center.
REFERENCES