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Journal of the American College of Nutrition, Vol. 19, No. 2, 275-284 (2000)
Published by the American College of Nutrition

Original Research

Weight Loss is Correlated with an Improved Lipoprotein Profile in Obese Postmenopausal Women

Zaida R. Cordero-MacIntyre, PhD, Timothy G. Lohman, PhD, Jason Rosen, BS, Warren Peters, MD, Richard C. España, BS, Barbara Dickinson, MS, RD, Phyllis M. Reid, MS, Wanda H. Howell, PhD and Maria Luz Fernandez, PhD

School of Public Health, Loma Linda University, Loma Linda, California (Z.R.C.-M., W.P., R.C.E., B.D.)
Department of Physiology (T.G.L.) University of Arizona, Tucson, Arizona
Department Nutritional Sciences (P.M.R., W.H.H.), University of Arizona, Tucson, Arizona
Department of Nutritional Sciences, University of Connecticut, Storrs, Connecticut (J.R., M.L.F.)

Address reprint requests to: Z.R. Cordero-MacIntyre, PhD, School of Public Health, Loma Linda University, Loma Linda, CA 92350


   ABSTRACT
TOP
 ABSTRACT
INTRODUCTION
 SUBJECTS AND METHODS
 RESULTS
 DISCUSSION
 REFERENCES
 
Background: Changes in plasma lipid and lipoprotein distributions that occur after menopause increase the risk of cardiovascular disease in women, especially in those who are overweight.

Objective: The purpose of this study was to evaluate the impact of a nine-month weight reduction program on plasma lipids, dietary intake and abdominal fat obesity.

Design: A partial crossover design was used to study a weight loss treatment consisting of Phentermine hydrochloride (Fastin®, SmithKline Beecham Pharmaceuticals, Philadelphia, PA) therapy plus a low energy diet (5040 kJ/d). Forty-seven obese, postmenopausal Caucasian women (BMI of 30–38 kg/m2) were randomized into two groups, both of which received drug and diet treatment over six months. However, Group I started the intervention program three months later than Group II. Plasma total, HDL and LDL cholesterol and triacylglycerol were measured, body composition was assessed by anthropometry and dual energy x-ray absorptiometry, and food frequency records were collected at four timepoints.

Results: Over nine months, women in Group II reduced body weight (14.4%), lowered plasma concentrations of LDL cholesterol (14% to 26%) and triacylglycerol (15%) and raised plasma HDL cholesterol concentration (15%). These plasma lipid changes decreased the total cholesterol/HDL cholesterol ratio from 4.3 to 3.2. All subjects decreased abdominal fat measurements and energy and cholesterol intakes, as well as percentage of energy derived from total and saturated fat during the study. Most subjects also increased dietary fiber consumption.

Conclusion: Both weight loss and diet modifications are associated with an improved plasma lipid profile in obese postmenopausal women.

Key words: weight reduction, postmenopause, plasma lipids, body composition, phenthermine hydrochloride


   INTRODUCTION
TOP
 ABSTRACT
 INTRODUCTION
SUBJECTS AND METHODS
 RESULTS
 DISCUSSION
 REFERENCES
 
Visceral fat obesity with predominant intra-abdominal fat accumulation has been associated with metabolic disorders. Vague et al. [1] identified two sub-categories of obesity, android and gynoid, signifying typically male or female body fat distributions, respectively, although both types occur in either gender. This classification represented the first association of android or visceral fat obesity with disease conditions such as diabetes mellitus, gout and atherosclerosis [1].

Alterations in body fat distribution have been associated with changes in lipids and lipoproteins and with increased coronary heart disease [2]. Evidence also suggests that cardiovascular disease risk increases prior to the onset of non-insulin dependent diabetes mellitus [3]. Examination of the roles of obesity, central body fat distribution and hyperinsulinemia revealed that these factors accounted for some of the characteristics associated with a less favorable cardiovascular disease risk pattern in subjects with impaired glucose tolerance [3].

Insulin resistance appears to be a syndrome associated with a clustering of metabolic disorders, including an atherogenic lipid profile [4]. Dyslipidemias (high plasma total cholesterol and triacylglycerol and low HDL cholesterol concentrations) have been strongly associated with hyperinsulinemia and high blood pressure in a mixed population of Mexican-Americans and non-Hispanic whites [5]. Furthermore, plasma lipoprotein concentrations are not significantly correlated with total fat mass, but with abdominal fat [6]. Data obtained by computerized axial tomography demonstrated that the absolute amount of deep abdominal fat is negatively correlated with HDL cholesterol concentrations, as well as with ratios of HDL to LDL cholesterol, HDL apolipoprotein A-I to LDL apolipoprotein B and HDL2 to HDL3 cholesterol [6]. Fujioka et al. [7] showed that the visceral/subcutaneous fat ratio is positively correlated with the plasma glucose area under the curve after glucose loading and with total cholesterol levels. These studies suggest that intra-abdominal fat may play a more pathogenic role or better reflect an underlying metabolic disorder, than subcutaneous fat in the development of diabetes mellitus or hyperlipidemia [6,7].

Some complications of obesity improve with weight loss [8]. Weight reduction in premenopausal women lowered visceral fat to a greater extent than abdominal subcutaneous fat. Decreases in the visceral/subcutaneous fat ratio and visceral fat volume were more strongly correlated with improvement in plasma glucose and lipid metabolism than reductions in body weight, BMI, total fat volume or abdominal subcutaneous fat volume [8].

It is also well established that after menopause, women undergo detrimental changes in plasma lipid and lipoprotein distributions that increase the risk of heart disease [9]. Postmenopausal women, specifically obese women presenting accumulation of visceral fat, may be at great risk for cardiovascular disease. Thus, the purpose of this study was to assess the effects of a weight loss program and the distribution of visceral fat on plasma lipids and dietary intake patterns. We hypothesized that 1) weight loss would result in an improved total to HDL cholesterol ratio and lower plasma triacylglycerol concentration, 2) weight loss would be significantly correlated with an improvement in lipoprotein profile and 3) weight loss would be associated with central visceral fat and changes in dietary intake of total energy, total fat as a percentage of energy and saturated fat as a percentage of energy.


   SUBJECTS AND METHODS
TOP
 ABSTRACT
 INTRODUCTION
 SUBJECTS AND METHODS
RESULTS
 DISCUSSION
 REFERENCES
 
Subjects
Postmenopausal Caucasian women 40 to 70 years of age were recruited by direct mailings and by an advertisement enclosed with Loma Linda University paychecks. A BMI of 30 kg/m2 plus a cardiovascular disease risk factor such as hypertension, diabetes mellitus, hyperlipidemia or degenerative joint disease were required for inclusion in the study. Exclusion criteria were participation in any weight control program during the previous three months, use of serotonin re-uptake inhibitors, untreated hypertension, hyperparathyroidism, hypersensitivity to sympathomimetic amines, glaucoma, agitated states, history of drug abuse, or use of monoamine oxidase inhibitors, either ongoing or within two weeks prior to recruitment. All subjects underwent an initial physical examination, a 12 lead electrocardiogram and blood tests that included complete blood count, lipid profile and random chemistry profile and had monthly check-ups by the study physician or nurse educator thereafter. Subjects were assigned to Group I or Group II using a random digits table. Of the 47 women who enrolled, 39 women completed the nine-month study. All subjects gave written informed consent to participate, and the study protocol was approved by the Loma Linda University Institutional Review Board.

Experimental Design
The study used a partial crossover design in which half of the subjects (Group II) began the weight loss intervention immediately, while the other half (Group I) delayed initiation of any weight loss intervention for three months. This design was used in order that the weight-stable Group I subjects could serve as the control for the weight-losing Group II subjects in a comparison of body composition variables measured by dual-energy x-ray absorptiometry (DXA).

A Phentermine hydrochloride (Fastin®, SmithKline Pharmaceuticals, Philadelphia, PA) dose of 15 mg/day was initially prescribed for Group II subjects. If a subject did not experience depressed appetite in response to this dose, the Fastin® dose was increased to 15 mg twice per day (8:00 A.M. and 5:00 P.M.). In addition to the drug therapy, a low calorie diet (5040 kJ/d) was prescribed, and attendance at monthly support sessions was required. The diet instructions included a recommendation to reduce saturated fat and cholesterol consumption, and to increase dietary fiber.

The support sessions provided skill-building techniques to encourage behavior changes in stress management, exercise, nutrition and management of emotions without excess food consumption. Patients were encouraged to set a goal for themselves, for example, walking. The guidelines of the American College of Sports Medicine were followed. These include an increase of 10% effort/week, which equals to approximately an increase of one to two minutes of exercise per week. In addition to the intake of 5040 kJ/d, nutritional counseling included recommendations to eat at regular meal times and to keep food records for self-monitoring. For the management of emotions, recommendations were made to deal with stressful situations; for example, instead of eating, subjects were urged to call a friend to vent feelings, to exercise or to do a pleasant task.

Groups I and II each received Phentermine hydrochloride therapy for six months, Group II from September to March and Group I from December to June. At the end of six months, Group II suspended Fastin® therapy, but continued the low energy diet and group sessions.

Food frequency dietary records were collected from all participants at baseline, 3, 6 and 9 months to ascertain compliance to the low energy diet and to assess dietary intakes of total and saturated fat, cholesterol and fiber. The Nutrient Profile Plus Program (Well Force Inc., Clackamas, OR) was used to calculate total energy, cholesterol and fiber intakes and percentage of energy derived from macro-nutrients and saturated fat.

Plasma Lipids
Two blood samples were obtained to determine plasma lipid (total, HDL and LDL cholesterol and triacylglycerol) concentrations at baseline, 3, 6 and 9 months for all subjects. Standardization and quality control for plasma total cholesterol and triacylglycerol assays have been maintained by participation in the Centers for Disease Control-National Heart, Lung and Blood Institute (CDC-NHLBI) Lipid Standardization Program since 1989. An enzymatic method [10] was used to determine plasma total cholesterol against cholesterol standards (Boehringer Mannheim Corp., Indianapolis, IN). Plasma HDL cholesterol was measured in the supernatant after precipitation of apolipoprotein B-containing lipoproteins [11], and LDL cholesterol was calculated as described by Friedewald et al. [12]. Plasma triacylglycerol was determined using the adjustment for free glycerol according to the method of Carr et al. [13].

Body Composition
Total and regional body composition was measured by DXA using the Hologic QDR-4500A instrument and body composition analysis software version 8.21 (Hologic Inc., Waltham, MA). Scans were obtained with the subject in the supine position, wearing only a hospital gown and undergarment and with metal and jewelry removed. Whole body scans were taken and regions of interest were isolated. Scan time was approximately three minutes for each assessment with a radiation exposure of 1.5 mrem. DXA scans were obtained at baseline, 3, 6 and 9 months for Group I subjects and at baseline, 3 and 6 months for Group II subjects.

Anthropometric measurements of height, weight, skinfold thickness at subscapular, triceps, suprailiac and abdominal sites and ratios of waist to hip (WHR) and waist to thigh (WTR) circumferences were made using standard protocols [14]. These measurements were conducted at baseline, 3, 6 and 9 months.

Statistical Analyses
Statistical analyses were performed using SPSS version 8.0 software (SPSS Inc. Chicago IL). Planned comparison paired t tests were used to assess differences over time (baseline, 3, 6 and 9 months) in the body composition, dietary intake and plasma lipid variables within each group. Independent t tests were used to compare body index measurements and lipid profiles between Group I and Group II at baseline and month 3 (before Group I began treatment). Pearson correlation coefficients were calculated to assess the impact of weight loss treatment on body composition while statistically adjusting for the effects of dietary intakes of saturated fat, cholesterol and fiber. Plasma lipid changes over time were correlated with changes in anthropometric measures at 3 and 6 months of treatment compared to baseline. Percentage mean difference was calculated as: Mean difference (%)=((baseline—3 or 6 or 9 months)/baseline)x100; where "baseline" is data obtained at baseline, and "3 or 6 or 9 months" is data obtained at either the 3, 6 or 9 month timepoint, respectively.


   RESULTS
TOP
 ABSTRACT
 INTRODUCTION
 SUBJECTS AND METHODS
 RESULTS
DISCUSSION
 REFERENCES
 
The descriptive characteristics of the subjects at baseline are summarized in Table 1. There were no differences in weight, age, height, plasma lipid values or most of the anthropometric measurements between Group I and Group II at baseline. WHR was, however, different (p <0.05) between groups with WHR larger for Group II.


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  		Table 1. Subjects Characteristics at Baseline1

 
As expected, subjects from Group I did not lose any weight over the first three months because they had not started the Phentermine hydrochloride treatment or the low energy diet (Table 2). In contrast, women in Group II had significant body weight losses of 7%, 11% and 14.5% compared to baseline over 3-, 6- and 9-month periods, respectively. An interesting observation was that after suspension of the Phentermine hydrochloride treatment (last 3 months), there was further weight loss by the women in Group II. Similarly, subjects in Group I lost 7% and 10% of their initial weight after 3- and 6-month of weight loss treatments, respectively. All subjects complied with Phentermine hydrochloride treatment as documented by records collected after each visit to the clinic.


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  		Table 2. Weight Loss by Two Groups of Postmenopausal Women during a Nine-Month Weight Reduction Program1

 
Comparisons of body weight loss were made between Group I and Group II to assess the efficacy of the weight reduction program. As indicated in Fig. 1, both groups had similar weight at baseline, and the weight loss was comparable during the six months of treatment that included Phentermine hydrochloride and low energy intake for both groups. These results indicate that the weight reduction program was effective for all participants independently of when they started the program (September vs. December). For purpose of comparison, baseline weights of Group I subjects and nine-month weights of Group II subjects are also shown.



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  		Fig. 1. Body weights of postmenopausal women during a six-month weight reduction program using Phentermine hydrochloride (Fastin®) plus 5040 kJ diet. Group I began treatment three months after Group II.

 
There were no differences between groups in total energy intake or percentage energy derived from fat, protein or carbohydrate or in dietary cholesterol and dietary fiber intakes at baseline (Table 3). However, after three months, Group II women had substantially decreased consumption of total energy, energy derived from total and saturated fat and dietary cholesterol and increased percentage energy from protein compared to baseline or to women in Group I. Although the self-reported energy intake was higher than the recommendation (6570 vs. 5040 kJ), energy intake was substantially reduced compared to baseline with a wide variation among individuals. These dietary changes affected plasma lipids as will be discussed later.


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  		Table 3. Comparison of Macronutrient and Saturated Fat, Dietary Fiber and Dietary Cholesterol Consumed by Postmenopausal Women before and after Three Months of Weight Loss Treatment1

 
Carbohydrate, total and saturated fat intakes for Group I assessed after 3 months were not different from baseline intakes as would be expected because these women had not yet begun the weight loss intervention (Fig. 2). By the sixth month of the study (after three months of intervention) significant decreases in percentage energy derived from total and saturated fat were observed for the Group I subjects (Fig. 2). These dietary changes continued through the nine-month period. However, similar to women in Group II, these subjects did not reduce energy intake to the recommended 5040 kJ, but had an average energy intake of 7268 kJ at three months and 6603 kJ at nine months with a broad range from 5800–8719 kJ.



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  		Fig. 2. Percent of energy derived from carbohydrate, total fat and saturated fat in subjects from Group I (upper panel) and Group II (lower panel) over nine months. Group I began treatment three months after Group II. Different superscripts indicate significantly different over time.

 
Subjects from Group II had significant reductions in energy intake with decreases in percentage of energy from saturated fat after three months coinciding with the time they started the weight reduction program (Fig. 2). The reduction in total energy and percentage energy from saturated fat persisted over nine months. However, although they were different from baseline (p <0.01), there were no differences between 3, 6 and 9 months. Energy intake was higher than the recommended 5040 kJ, ranging from 4733 to 8043 kJ/d. There were other important dietary changes in Group II. In addition, subjects from Groups I and II had lower intake of cholesterol over 6 and 9 months compared to baseline and subjects from Group II had higher intake of dietary fiber at 6 and 9 months compared to baseline (Fig. 3).



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  		Fig. 3. Total fiber and dietary cholesterol (x10) in g/day fat in subjects from Group I (upper panel) and Group II (lower panel) over nine months. Group I began treatment three months after Group II. Different superscripts indicate significantly different over time.

 
Plasma total cholesterol concentrations were significantly lowered over time for both Group I and Group II (p <0.01) (Table 4). For Group I, plasma total cholesterol did not decrease during the first three months before weight loss treatment began. However, total cholesterol was significantly reduced by 13.0% and 19.9% at 6 and 9 months after baseline, respectively (or 3 and 6 months respectively after treatment was started). For Group II, the reductions were 9.3% over 3 and 6 months and 13.6% over 9 months (p <0.01). Similar results were obtained for plasma LDL cholesterol concentrations (Table 4). Group I had 14.4% and 32.0% reductions in plasma LDL cholesterol compared to baseline after 3 and 6 months of weight loss intervention, respectively. However, in agreement with the finding of no weight loss, plasma LDL cholesterol concentration did not decrease between baseline and three months for this group. In contrast, subjects from Group II reduced plasma LDL cholesterol by 9.7% over three months and had further reductions of 11.6% and 24.6% over 6 and 9 months, respectively. Plasma HDL cholesterol concentrations were affected by weight loss (Table 4). Individuals from Group I raised plasma HDL cholesterol concentration by 13.4% after only 6 months (9 months from baseline) of weight reduction treatment. Subjects in Group II had a 4.3% increase in HDL cholesterol after six months of treatment which was significant (p <0.05) and a further 17.2% increase after nine months.


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  		Table 4. Plasma Total Cholesterol, LDL-Cholesterol, HDL-Cholesterol Triglycerides and LDL/HDL Ratios in Postmenopausal Women Over a Nine-Month Weight Loss Period

 
Plasma triacylglycerol concentrations were reduced (p <0.01) by an average of 18.3% over nine months in subjects from Group I (Table 4). In contrast, individuals from Group II experienced a decrease of 14.7% in plasma triacylglycerol after three months that was sustained through the nine months of the study. The total cholesterol/HDL cholesterol ratio, the best predictor for coronary heart disease, was decreased by 29.7% over nine months for Group I and by 27.2% for Group II (Table 4).

When comparisons were made during the time of the weight reduction program for both groups, there were no differences in plasma total cholesterol concentrations between groups at baseline or during the six months of treatment (Fig. 4A), indicating that plasma total cholesterol decreased in parallel with weight. Similarly the effectiveness of the weight loss program was confirmed by comparing plasma LDL cholesterol concentrations after 3 and 6 months of treatment (6 and 9 months from baseline for Group I) (Fig. 4B). Correlation of changes in plasma HDL cholesterol between groups revealed no significant differences over nine months (Fig. 4C). The effect of Fastin® plus low energy intake on plasma triacylglycerol was also compared between the two groups (Fig. 4D) and no significant changes were observed over the six months of treatment.



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  		Fig. 4. Plasma concentrations of total cholesterol (TC; panel A), LDL cholesterol (LDL-C; panel B), HDL cholesterol (HDL-C; panel C) and triacylglycerol (TAG; panel D) of postmenopausal women during a six-month weight reduction program using Phentermine hydrochloride (Fastin®) plus 5040 kJ diet. Group I delayed initiation of treatment for three months (time period indicated as "Pre-"); Group II discontinued Phentermine hydrochloride after six months, but continued the 5040 kJ diet through nine months (time period indicated as "Post-").

 
Anthropometry measurements, including those evaluated by DXA (fat mass, abdominal fat mass and thigh fat mass) and BMI did not differ between baseline and three months for Group I because these subjects had not started the weight loss treatment (Table 5). In contrast, there were very significant (p <0.01) reductions in all of these parameters, except the abdominal skinfold measurement, for Group II subjects after three months of treatment. Group I subjects had significant decreases in fat mass, thigh and abdominal fat, BMI and skinfold measurements after 6 and 9 months compared to either the baseline or the three-month measurements. Subjects from Group II had significant reductions in anthropometric measurements over nine months compared to baseline. However, with the exception of the abdominal skinfold that did not improve until the six month measurement, all of the improvement in skinfold measurements occurred by the end of the first three months. In contrast, BMI and WHR were significantly lower after 6 and 9 months compared to the measures at three months.


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  		Table 5. Anthropometry Measurements and Fat Distribution of Postmenopausal Women Over a Nine-Month Weight Loss Period

 
Because all subjects experienced similar changes in plasma lipids and anthropometric measurements during the six months of treatment (6 and 9 months after baseline for Group I and 3 and 6 months after baseline for Group II), all data were pooled to evaluate whether changes in plasma lipids corresponded to changes in anthropometric measurements. After adjusting for dietary factors, including saturated fat, cholesterol and fiber, change in BMI was the most consistent factor that correlated positively with changes in plasma total cholesterol, LDL cholesterol and triacylglycerol and negatively with HDL cholesterol after three months of treatment (Table 6). Decreases in weight and thigh fat mass were also correlated with total cholesterol, LDL cholesterol and triacylglycerol, while loss of abdominal fat mass was correlated with only total and LDL cholesterol. Some of the skinfold measurements correlated as expected with changes in plasma lipids after three months of treatment. Changes in plasma triacylglycerol correlated (p <0.01) with decreases in skinfold measurements after six months of treatment. Changes in HDL cholesterol were negatively correlated with BMI and weight after six months, and changes in LDL cholesterol were positively correlated with triceps and suprailiac skinfolds and with changes in BMI. Changes in plasma total cholesterol were positively correlated with changes in triceps and abdominal skinfolds after six months.


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  		Table 6. Significant Correlations between Changes in Plasma Lipids and Anthropometric Measurements for Postmenopausal Women during a Weight Reduction Treatment1

 

   DISCUSSION
TOP
 ABSTRACT
 INTRODUCTION
 SUBJECTS AND METHODS
 RESULTS
 DISCUSSION
REFERENCES
 
This study was conducted with free-living subjects over a period of nine months. It was anticipated that Phentermine hydrochloride therapy in combination with low energy intake would result in a 10% reduction in body weight during this time. Results of the study fulfilled this expectation. The cumulative weight loss over nine months for Group I was 10.0% (10.65 kg) and for Group II was 14.4% (13.72 kg). Other studies have reported similar weight losses in the range of 12 to 13 kg [5, 16–18] in obese women (BMI 35–41 kg/m2) undergoing weight loss programs ranging from 8 to 52 weeks. Podenphant et al. [19] reported a 4.5 kg weight loss over three months in a group of female and male subjects who were 10% overweight, and Pritchard et al. [20] found a weight loss of 6.4 kg in male subjects with a BMI of 29 kg/m2 who followed a low fat diet. The weight loss achieved by the subjects in the present study is within the ranges observed by other investigators [5, 16–20].

It is possible that the weight loss program would have been more successful in this study if the participating women had more strictly followed the recommended low energy diet (5040 kJ); however, although Fastin® is an anorectic drug [21], the women still consumed a higher amount of energy. The degree of compliance to low energy intake by the subjects varied and could have been related to individual motivation and participation in support groups, especially for those subjects who suspended Fastin® treatment (Group II).

Plasma lipid and lipoprotein cholesterol concentrations are significantly influenced by weight loss [22] and by diet [23]. Subjects in the present study not only lost weight, but also had significant modifications in diet that could be related to changes in plasma lipids. These dietary modifications included decreased saturated fat and cholesterol and increased dietary fiber and energy from carbohydrates. Thus, the effects of weight loss and diet and their influence on plasma lipids will be analyzed separately.

Body Weight Reduction and Plasma Lipids
Throughout the study, changes observed in plasma lipids and lipoproteins paralleled weight loss. Significant decreases in plasma LDL cholesterol and triacylglycerol and increases in HDL cholesterol concentrations were observed over the nine-month period. These findings are in agreement with other studies reporting a negative correlation between BMI, WHR and lipid and lipoprotein fractions [4] or between BMI and total cholesterol [7], as well as decreased plasma concentrations of total cholesterol and triacylglycerol [7] with weight reduction.

Depres et al. [6] found a negative correlation between BMI, WHR and lipid and lipoprotein fractions, as well as decreased total cholesterol and triacylglycerol concentrations with weight reduction. It has been suggested that the preponderance of ß-adrenergic receptors with relatively little {alpha}-adrenergic inhibition in intra-abdominal adipose tissue provides a sensitive system for mobilization of FFA [24]. When the liver is exposed to high concentrations of FFA, several important metabolic consequences might occur, such as increased VLDL synthesis that in turn leads to increased formation of LDL in the intravascular compartment. The increased synthesis of VLDL might be related to excess production of apolipoprotein B and the increased VLDL secretion to the excess synthesis of triacylglycerol that is dependent on FFA availability [24]. Because both synthesis and catabolism regulate plasma LDL cholesterol concentrations, the higher plasma LDL cholesterol concentrations associated with intra-abdominal adiposity can be related to increased formation of LDL through the delipidation cascade [25].

In agreement with this theory of the mobilization of FFA, weight loss in obese postmenopausal women in this study was associated with decreased intra-abdominal fat, lower plasma total cholesterol and triacylglycerol. Because LDL is the major carrier of cholesterol in plasma and VLDL is the major carrier of triacylglycerol in the fasting state, the observed decreases in plasma lipids can be related to the postulated decreased synthesis of VLDL [26], which in turn lowers the formation of LDL in the plasma compartment. Interestingly, in the present study, decreases in total fat and abdominal fat were positively correlated with decreases in plasma LDL cholesterol after three months of treatment after controlling for diet; this finding agrees with the theory of decreased LDL formation [26]. However, after six months the correlation with abdominal fat no longer existed, suggesting that diet had a major effect because plasma LDL cholesterol concentration continued to decrease. Another important modification was the increase in plasma HDL cholesterol that is associated with decreased risk of coronary heart disease. In this study, plasma triacylglycerol concentration decreased with weight reduction while plasma HDL cholesterol increased. It is well known that a strong negative association exists between plasma triacylglycerol-rich lipoprotein and HDL cholesterol concentrations [27]; thus, metabolic manipulations that modify plasma triacylglycerol will also affect HDL cholesterol concentration. In addition, at baseline the obese women in the present study had low plasma HDL cholesterol concentrations compared to reports in the literature [28, 29]. Clifton et al. [29] demonstrated that the most important predictor of change in HDL cholesterol concentration in women is WHR and baseline cholesterol, while in men BMI plays a significant role. Similarly to observations in men, a significant reduction in the BMI of obese postmenopausal women in this study correlated with increased HDL cholesterol concentration. We could postulate that these increases are related to normalization of plasma HDL cholesterol to levels commonly observed in non-obese postmenopausal Caucasian women [28, 29].

The significant decrease in abdominal fat mass measured by DXA and in subscapular, triceps, suprailiac and abdominal skinfolds with decreasing weight clearly indicates that weight loss was not only from the arms (triceps), but from centrally distributed adipose tissue. It was of particular interest to notice that WHR decreased after only three months of the weight reduction program. This desirable effect on abdominal adiposity produced a positive effect on plasma lipid profile.

Diet and Plasma Lipids
It is well recognized that diet plays a major role in plasma lipid profiles [23]; thus, the decreases in plasma concentrations of LDL cholesterol and triacylglycerol and increase in plasma HDL cholesterol concentration observed in postmenopausal women during weight reduction were partly due to changes in diet.

Decreases in saturated fat intake have been associated with decreases in plasma LDL cholesterol concentration in numerous clinical trials [30, 31]. The mechanisms involved may be related to decreased secretion of VLDL [32] or to increased hepatic apolipoprotein B/E receptors as reported in animal studies [33–35] or to increased LDL receptors in isolated monocytes as reported in clinical trials [36]. The observed decrease in LDL cholesterol during weight loss by postmenopausal women may be due, in part, to the self-reported decrease in energy derived from saturated fat. There is much speculation about the role of dietary cholesterol on plasma lipids [37, 38]. A recently published meta-analysis including 224 studies with 8143 individuals, both free-living subjects and metabolic ward patients, reported that decreasing dietary cholesterol from the average 385 mg/d to 300 mg/d would reduce plasma total cholesterol only by 1.9 mg/dL [39]. According to that study, reducing dietary fat content from 37 to 30% and saturated fat from 13 to 10% would decrease plasma cholesterol by 5.8 mg/dL, a more significant response [39]. Hu et al. [40] demonstrated that saturated fat and trans fatty acids were significant predictors of coronary heart disease, while dietary cholesterol had no major effect.

Subjects in the present study reduced dietary cholesterol intake by decreasing consumption of animal products; this was highly associated with decreased saturated fat and increased dietary fiber intakes. Dietary fiber may also have had a major role in the observed decreases in plasma LDL cholesterol as has been reported in clinical trials [41, 42] and animal studies [43, 44]. Similar to our data, Andersen et al. [45] reported that in obese women, modest weight losses were associated with improved lipid profiles and that dietary energy and macronutrient composition contributed significantly to the observed improvement.

An important aspect of this study is that in both groups of women all of the reduction in plasma triacylglycerol concentration occurred during the first six months, and there was a trend for the concentration to increase thereafter. It has been well established that high carbohydrate, low fat diets result in elevated plasma triacylglycerol concentration and lower plasma HDL cholesterol concentration [46]. This may be one reason why plasma triacylglycerol did not continue to decrease after the first three months of treatment. Although weight reduction is related to significant decreases in plasma triacylglycerol [7], the low fat, high carbohydrate diet might have blunted that effect [47]. Plasma HDL cholesterol concentration was highest after nine months for both groups of subjects which suggests a major role of weight loss in this plasma variable as indicated by the negative correlations between anthropometric measures and plasma HDL cholesterol concentration.

Although the subjects in this study did not consume the recommended low energy diet, an improvement in plasma lipid profile was achieved by a combination of drug-assisted weight loss and changes in dietary patterns. Specifically weight loss was accompanied by a reduction in total energy intake, total fat as a percentage of energy, saturated fat as a percentage of energy and an increase in dietary fiber intake.

The present study emphasizes the importance of the multifactorial nature of life style changes, which influence plasma lipid levels. Although it is well known that body weight reduction is associated with an improved lipoprotein profile [7] and that decreasing saturated fat [40] and increasing dietary fiber [42] results in decreases in plasma LDL-cholesterol concentrations, it was of great interest to observe the predicted responses in our obese postmenopausal subjects. Since the dyslipidemias associated with obesity have a major contribution to morbidity and mortality [3], weight intervention programs focused on dietary changes are of great importance in reducing risk factors for coronary heart disease, diabetes and insulin resistance.


   FOOTNOTES
 
Supported by the Center for Health Research and the Nutrition Department of the Loma Linda University School of Public Health and by the Loma Linda University Cancer Institute.

Received July 1, 1999. Accepted September 1, 1999.


   REFERENCES
TOP
 ABSTRACT
 INTRODUCTION
 SUBJECTS AND METHODS
 RESULTS
 DISCUSSION
 REFERENCES
 

  1. Vague J, Vague P, Meignen J-M, Jubelin J, Tramoni M: Android and gynoid obesities, past and present. In Vague J, Bjorntorp P, Guy-Grand B, Rebuffe-Scribe N, Vague P (eds): "Metabolic Complications of Human Obesities." Proceedings of the 6th International Meeting of Endocrinology, Marseille, 30 May–1 June. Amsterdam: Exerpta Medica 1985: 3–11, 1985.
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