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1.  Elevated Soluble Lectin-like Oxidized LDL Receptor 1 (LOX-1) Levels in Obese Postmenopausal Women 
Obesity (Silver Spring, Md.)  2008;16(6):1454-1456.
We investigated the association between soluble lectin-like oxidized LDL receptor 1 (sLOX-1) levels and obesity in older women. Fifty-one (10 lean, 22 overweight, and 19 obese) postmenopausal women were included in this small retrospective analysis. Plasma sLOX-1 levels were measured using a chemiluminescent ELISA. Plasma levels of sLOX-1 were significantly higher in obese women (55.33±4.49 pg/mL) compared to lean (30.91±6.19 pg/mL, p=0.002) and overweight women (38.31±4.18 pg/mL, p=0.017). Plasma sLOX-1 levels were positively associated with body weight, BMI, total body fat, and trunk fat. The relationship between sLOX-1 and BMI was attenuated after adjustment for age, HRT, and body fat. In conclusion, obese women have higher sLOX-1 levels, which may reflect increased LOX-1 expression in adipose tissue.
doi:10.1038/oby.2008.213
PMCID: PMC2677801  PMID: 18388896
obesity; postmenopausal women; receptors
2.  Variation in the Lectin-like Oxidized LDL Receptor 1 (LOX-1) Gene Is Associated With Plasma Soluble LOX-1 Levels 
Experimental physiology  2008;93(9):1085-1090.
The lectin-like ox-LDL receptor 1 (LOX-1) expressed on vascular cells plays a major role in atherogenesis by internalizing and degrading oxidized LDL. LOX-1 can be cleaved from the cell surface and released as soluble LOX-1 (sLOX-1), and elevated sLOX-1 levels may be indicative of atherosclerotic plaque instability. We examined associations between the LOX-1 3′UTR-C/T and G501C polymorphisms and plasma sLOX-1 levels in 97 healthy older men and women. The frequencies for the 3′UTR-T and 501C alleles were 46% and 10%, respectively. Plasma sLOX-1 levels were significantly higher in the 3′UTR CC genotype group compared to both the CT (p=0.02) and TT (p=0.002) genotype groups. Plasma sLOX-1 were also significantly higher in the 501GC genotype group compared to the GG genotype group (p=0.004). In univariate analyses, sLOX-1 levels were significantly associated with both the 3′UTR-C/T and G501 C polymorphisms. These associations remained significant after adjusting for age, gender, race, and BMI. In conclusion, variation in the LOX-1 gene is associated with plasma sLOX-1 levels in older men and women.
doi:10.1113/expphysiol.2008.042267
PMCID: PMC2652129  PMID: 18469066
receptor; cardiovascular; gene expression
3.  Pregnancy Followed by Delivery May Affect Circulating Soluble Lectin-Like Oxidized Low-Density Lipoprotein Receptor-1 Levels in Women of Reproductive Age 
Mediators of Inflammation  2012;2012:837375.
Background/Objective. It is known that menopause or lack of endogenous estrogen is a risk factor for endothelial dysfunction and CAD. Lectin-like oxidized low-density lipoprotein receptor-1 (LOX-1) is involved inmultiple phases of vascular dysfunction.The purpose of the current study was to determine the association between soluble LOX-1 (sLOX-1) and pregnancy followed by delivery in women of reproductive age. Materials/Methods. Sixty-eight subjects with pregnancy followed by delivery (group 1) and 57 subjects with nongravidity (group 2) were included in this study. Levels of sLOX-1 were measured in serum by EL SA. Results. Plasma levels of sLOX-1 were significantly lower in Group 1 than Group 2 in women of reproductive age (0.52 ± 0.18 ng/mL and 0.78 ± 0.13, resp., P < 0.001). There were strong correlations between sLOX-1 levels and the number of gravida (r = −0.645, P < 0.001). The levels of sLOX-1 highly correlated with the number of parous (r = −0.683, P < 0.001). Conclusion. Our study demonstrated that serum sLOX-1 levels were associated with pregnancy followed by delivery that might predict endothelial dysfunction. We conclude that pregnancy followed by delivery may delay the beginning and progress of arteriosclerosis and its clinical manifestations in women of reproductive age.
doi:10.1155/2012/837375
PMCID: PMC3350984  PMID: 22619487
4.  Acute Impact of Moderate-Intensity and Vigorous-Intensity Exercise Bouts on Daily Physical Activity Energy Expenditure in Postmenopausal Women 
Journal of Obesity  2010;2011:342431.
This study determined whether performing a single moderate- or vigorous-intensity exercise bout impacts daily physical activity energy expenditure (PAEE, by accelerometer). Overweight/obese postmenopausal women underwent a 5-month caloric restriction and moderate- (n = 18) or vigorous-intensity (n = 18) center-based aerobic exercise intervention. During the last month of intervention, in women performing moderate-intensity exercise, PAEE on days with exercise (577.7 ± 219.7 kcal·d−1) was higher (P = .011) than on days without exercise (450.7 ± 140.5 kcal·d−1); however, the difference (127.0 ± 188.1 kcal·d−1) was much lower than the energy expended during exercise. In women performing vigorous-intensity exercise, PAEE on days with exercise (450.6 ± 153.6 kcal·d−1) was lower (P = .047) than on days without exercise (519.2 ± 127.4 kcal·d−1). Thus, women expended more energy on physical activities outside of prescribed exercise on days they did NOT perform center-based exercise, especially if the prescribed exercise was of a higher intensity.
doi:10.1155/2011/342431
PMCID: PMC2931398  PMID: 20847895
5.  Adipose tissue endocannabinoid system gene expression: depot differences and effects of diet and exercise 
Background
Alterations of endocannabinoid system in adipose tissue play an important role in lipid regulation and metabolic dysfunction associated with obesity. The purpose of this study was to determine whether gene expression levels of cannabinoid type 1 receptor (CB1) and fatty acid amide hydrolase (FAAH) are different in subcutaneous abdominal and gluteal adipose tissue, and whether hypocaloric diet and aerobic exercise influence subcutaneous adipose tissue CB1 and FAAH gene expression in obese women.
Methods
Thirty overweight or obese, middle-aged women (BMI = 34.3 ± 0.8 kg/m2, age = 59 ± 1 years) underwent one of three 20-week weight loss interventions: caloric restriction only (CR, N = 9), caloric restriction plus moderate-intensity aerobic exercise (CRM, 45-50% HRR, N = 13), or caloric restriction plus vigorous-intensity aerobic exercise (CRV, 70-75% HRR, N = 8). Subcutaneous abdominal and gluteal adipose tissue samples were collected before and after the interventions to measure CB1 and FAAH gene expression.
Results
At baseline, FAAH gene expression was higher in abdominal, compared to gluteal adipose tissue (2.08 ± 0.11 vs. 1.78 ± 0.10, expressed as target gene/β-actin mRNA ratio × 10-3, P < 0.05). Compared to pre-intervention, CR did not change abdominal, but decreased gluteal CB1 (Δ = -0.82 ± 0.25, P < 0.05) and FAAH (Δ = -0.49 ± 0.14, P < 0.05) gene expression. CRM or CRV alone did not change adipose tissue CB1 and FAAH gene expression. However, combined CRM and CRV (CRM+CRV) decreased abdominal adipose tissue FAAH gene expression (Δ = -0.37 ± 0.18, P < 0.05). The changes in gluteal CB1 and abdominal FAAH gene expression levels in the CR alone and the CRM+CRV group were different (P < 0.05) or tended to be different (P = 0.10).
Conclusions
There are depot differences in subcutaneous adipose tissue endocannabinoid system gene expression in obese individuals. Aerobic exercise training may preferentially modulate abdominal adipose tissue endocannabinoid-related gene expression during dietary weight loss.
Trial Registration
ClinicalTrials.gov: NCT00664729.
doi:10.1186/1476-511X-10-194
PMCID: PMC3213035  PMID: 22035053
Cannabinoid Type 1 Receptor; Fatty Acid Amide Hydrolase; Fat Depots; Diet; Exercise
6.  Changes in Weight, Waist Circumference and Compensatory Responses with Different Doses of Exercise among Sedentary, Overweight Postmenopausal Women 
PLoS ONE  2009;4(2):e4515.
Background
It has been suggested that exercise training results in compensatory mechanisms that attenuate weight loss. However, this has only been examined with large doses of exercise. The goal of this analysis was to examine actual weight loss compared to predicted weight loss (compensation) across different doses of exercise in a controlled trial of sedentary, overweight or obese postmenopausal women (n = 411).
Methodology/Principal Findings
Participants were randomized to a non-exercise control (n = 94) or 1 of 3 exercise groups; exercise energy expenditure of 4 (n = 139), 8 (n = 85), or 12 (n = 93) kcal/kg/week (KKW). Training intensity was set at the heart rate associated with 50% of each woman's peak VO2 and the intervention period was 6 months. All exercise was supervised. The main outcomes were actual weight loss, predicted weight loss (exercise energy expenditure/ 7700 kcal per kg), compensation (actual minus predicted weight loss) and waist circumference. The study sample had a mean (SD) age 57.2 (6.3) years, BMI of 31.7 (3.8) kg/m2, and was 63.5% Caucasian. The adherence to the intervention was >99% in all exercise groups. The mean (95% CI) weight loss in the 4, 8 and 12 KKW groups was −1.4 (−2.0, −0.8), −2.1 (−2.9, −1.4) and −1.5 (−2.2, −0.8) kg, respectively. In the 4 and 8 KKW groups the actual weight loss closely matched the predicted weight loss of −1.0 and −2.0 kg, respectively, resulting in no significant compensation. In the 12 KKW group the actual weight loss was less than the predicted weight loss (−2.7 kg) resulting in 1.2 (0.5, 1.9) kg of compensation (P<0.05 compared to 4 and 8 KKW groups). All exercise groups had a significant reduction in waist circumference which was independent of changes in weight.
Conclusion
In this study of previously sedentary, overweight or obese, postmenopausal women we observed no difference in the actual and predicted weight loss with 4 and 8 KKW of exercise (72 and 136 minutes respectively), while the 12 KKW (194 minutes) produced only about half of the predicted weight loss. However, all exercise groups had a significant reduction in waist circumference which was independent of changes in weight.
Trial Registration
ClinicalTrials.gov NCT 00011193
doi:10.1371/journal.pone.0004515
PMCID: PMC2639700  PMID: 19223984
7.  Moderate Exercise Attenuates the Loss of Skeletal Muscle Mass That Occurs With Intentional Caloric Restriction–Induced Weight Loss in Older, Overweight to Obese Adults 
Background
Aging is associated with a loss of muscle mass and increased body fat. The effects of diet-induced weight loss on muscle mass in older adults are not clear.
Purpose
This study examined the effects of diet-induced weight loss, alone and in combination with moderate aerobic exercise, on skeletal muscle mass in older adults.
Methods
Twenty-nine overweight to obese (body mass index = 31.8 ± 3.3 kg/m2) older (67.2 ± 4.2 years) men (n = 13) and women (n = 16) completed a 4-month intervention consisting of diet-induced weight loss alone (WL; n = 11) or with exercise (WL/EX; n = 18). The WL intervention consisted of a low-fat, 500–1,000 kcal/d caloric restriction. The WL/EX intervention included the WL intervention with the addition of aerobic exercise, moderate-intensity walking, three to five times per week for 35–45 minutes per session. Whole-body dual-energy x-ray absorptiometry, thigh computed tomography (CT), and percutaneous muscle biopsy were performed to assess changes in skeletal muscle mass at the whole-body, regional, and cellular level, respectively.
Results
Mixed analysis of variance demonstrated that both groups had similar decreases in bodyweight (WL, −9.2% ± 1.0%; WL/EX, −9.1% ± 1.0%) and whole-body fat mass (WL, −16.5%, WL/EX, −20.7%). However, whole-body fat-free mass decreased significantly (p < .05) in WL (−4.3% ± 1.2%) but not in WL/EX (−1.1% ± 1.0%). Thigh muscle cross-sectional area by CT decreased in both groups (WL, −5.2% ± 1.1%; WL/EX, −3.0% ± 1.0%) and was not statistically different between groups. Type I muscle fiber area decreased in WL (−19.2% ± 7.9%, p = .01) but remained unchanged in WL/EX (3.4% ± 7.5%). Similar patterns were observed in type II fibers (WL, −16.6% ± 4.0%; WL/EX, −0.2% ± 6.5%).
Conclusion
Diet-induced weight loss significantly decreased muscle mass in older adults. However, the addition of moderate aerobic exercise to intentional weight loss attenuated the loss of muscle mass.
doi:10.1093/gerona/glp007
PMCID: PMC2800807  PMID: 19276190
Weight loss; Aerobic exercise; Obese; Muscle
8.  A randomized clinical trial of home-based exercise combined with a slight caloric restriction on obesity prevention among women 
Preventive medicine  2010;51(3-4):247-252.
Objective
The study investigated the effectiveness of home-based exercise combined with a slight caloric restriction on weight change during 12 months in non obese women.
Methods
A randomized clinical trial with a factorial design was conducted from 2003 to 2005. Two hundred three middle-aged women (Rio de Janeiro/Brazil), 25–45 years, were randomly assigned to one of two groups: control (CG) and home-based exercise (HB). The HB group received a booklet on aerobic exercise that could be practiced at home (3 times/week - 40 min/session), in low-moderate intensity, during 12 months. Both groups received dietary counseling aimed at a slight energy restriction of 100–300 calories per day.
Results
The HB experienced a greater weight loss in the first 6 months (−1.4 vs. −0.8 kg; p=0.04), but after 12 months there was no differences between groups (−1.1 vs. −1.0; p=0.20). Of the serum biochemical markers, HDL-cholesterol showed major change, with an increase at month 12 of 18.3 mg/dl in the HB compared to 9.5 in the CG (p<0.01).
Conclusion
Home-based exercise promoted greater weight reduction during the first six months after which no further benefits are observed. Continuous favorable changes in HDL-cholesterol after 1 year suggest that home-based exercise promote health benefits.
doi:10.1016/j.ypmed.2010.07.012
PMCID: PMC2939161  PMID: 20654643
9.  Dietary weight loss and exercise interventions effects on quality of life in overweight/obese postmenopausal women: a randomized controlled trial 
Background
Although lifestyle interventions targeting multiple lifestyle behaviors are more effective in preventing unhealthy weight gain and chronic diseases than intervening on a single behavior, few studies have compared individual and combined effects of diet and/or exercise interventions on health-related quality of life (HRQOL). In addition, the mechanisms of how these lifestyle interventions affect HRQOL are unknown. The primary aim of this study was to examine the individual and combined effects of dietary weight loss and/or exercise interventions on HRQOL and psychosocial factors (depression, anxiety, stress, social support). The secondary aim was to investigate predictors of changes in HRQOL.
Methods
This study was a randomized controlled trial. Overweight/obese postmenopausal women were randomly assigned to 12 months of dietary weight loss (n = 118), moderate-to-vigorous aerobic exercise (225 minutes/week, n = 117), combined diet and exercise (n = 117), or control (n = 87). Demographic, health and anthropometric information, aerobic fitness, HRQOL (SF-36), stress (Perceived Stress Scale), depression [Brief Symptom Inventory (BSI)-18], anxiety (BSI-18) and social support (Medical Outcome Study Social Support Survey) were assessed at baseline and 12 months. The 12-month changes in HRQOL and psychosocial factors were compared using analysis of covariance, adjusting for baseline scores. Multiple regression was used to assess predictors of changes in HRQOL.
Results
Twelve-month changes in HRQOL and psychosocial factors differed by intervention group. The combined diet + exercise group improved 4 aspects of HRQOL (physical functioning, role-physical, vitality, and mental health), and stress (p ≤ 0.01 vs. controls). The diet group increased vitality score (p < 0.01 vs. control), while HRQOL did not change differently in the exercise group compared with controls. However, regardless of intervention group, weight loss predicted increased physical functioning, role-physical, vitality, and mental health, while increased aerobic fitness predicted improved physical functioning. Positive changes in depression, stress, and social support were independently associated with increased HRQOL, after adjusting for changes in weight and aerobic fitness.
Conclusions
A combined diet and exercise intervention has positive effects on HRQOL and psychological health, which may be greater than that from exercise or diet alone. Improvements in weight, aerobic fitness and psychosocial factors may mediate intervention effects on HRQOL.
doi:10.1186/1479-5868-8-118
PMCID: PMC3215656  PMID: 22026966
health-related quality of life; exercise; dietary weight loss; postmenopausal women
10.  Effect of diet and exercise, alone or combined, on weight and body composition in overweight-to-obese post-menopausal women 
Obesity (Silver Spring, Md.)  2011;20(8):1628-1638.
Lifestyle interventions for weight loss are the cornerstone of obesity therapy, yet their optimal design is debated. This is particularly true for postmenopausal women; a population with a high prevalence of obesity yet towards whom fewer studies are targeted. We conducted a year-long, 4-arm randomized trial among 439 overweight-to-obese postmenopausal sedentary women to determine the effects of a calorie-reduced, low-fat diet (D), a moderate-intensity, facility-based aerobic exercise program (E), or the combination of both interventions (D+E), vs. a no-lifestyle-change control (C) on change in body weight and composition. The group-based dietary intervention had a weight-reduction goal of ≥10%, and the exercise intervention consisted of a gradual escalation to 45 min aerobic exercise 5 d/wk. Participants were predominantly non-Hispanic Whites (85%) with a mean age of 58.0±5.0 years, a mean BMI of 30.9±4.0 kg/m2 and an average of 47.8±4.4% body fat. Baseline and 12-month weight and adiposity measures were obtained by staff blinded to participants’ intervention assignment. 399 women completed the trial (91% retention). Using an intention-to-treat analysis, average weight loss at 12 months was −8.5% for the D group (P<0.0001 vs. C), −2.4% for the E group (P=0.03 vs. C), and −10.8% for the D+E group (P<0.0001 vs. C), while the C group experienced a non-significant −0.8% decrease. BMI, waist circumference, and % body fat were also similarly reduced. Among postmenopausal women, lifestyle change involving diet, exercise, or both combined over 1 year improves body weight and adiposity, with the greatest change arising from the combined intervention.
doi:10.1038/oby.2011.76
PMCID: PMC3406229  PMID: 21494229
Body weight; body composition; weight-reducing diet; exercise intervention; women
11.  Dilemmas in the process of weight reduction: Exploring how women experience training as a means of losing weight 
Patients diagnosed with obesity are usually offered group-based behavior interventions which include dietary advice and exercise programs. In particular, high-intensity training—combining weight lifting with aerobic exercising—has been proven effective for losing weight. Moreover, recent studies have shown that persons participating in high-intensity training are more likely to maintain their weight loss compared to persons with lower levels of physical activity. However, most of the research in the field has made use of quantitative methods focusing on the measurable effect of such interventions. Therefore, the aim of this study was to show how the training is experienced from a first-person perspective, namely the patients themselves. Our hope was to shed some new light on the process of weight loss that concerns more than the measurable “impacts” of the training. A qualitative approach was used based on interviews with five women selected from a primary healthcare clinic in Norway. Our results show that experiences of training are connected to the participants' general experience of being overweight. Both relationships to other people and earlier experiences are important for how the training is carried out and perceived. Five themes were identified supporting this line of argument: (1) the gaze of others; (2) a common ground; (3) dependence of close-follow up; (4) bodily discomfort as painful; and (5) aiming for results—an ambivalent experience. The results highlight the importance of finding the proper context and support for each patient's needs.
doi:10.3402/qhw.v5i2.5125
PMCID: PMC2875968  PMID: 20640017
Obesity; weight reduction; exercise; qualitative study; group treatment
12.  Effects of Different Doses of Physical Activity on C-Reactive Protein Among Women 
Elevated C-reactive protein (CRP) is associated with an increased risk of cardiovascular disease. Physical activity has been inversely associated with CRP. However, the clinical trials examining the effect of exercise training have produced conflicting results.
Purpose
The purpose of this study was to examine the influence an exercise training program on CRP in postmenopausal women.
Methods
Sedentary, overweight/obese, postmenopausal women with elevated systolic blood pressure (120.0 to 159.9 mm Hg) (N= 464) were randomized into 1 of 4 groups: a non-exercise control or 1 of 3 aerobic exercise groups; exercise energy expenditure of 4, 8, or 12 kcal/kg/week (KKW), for 6 months at a training intensity of 50% of peak VO2.
Results
Complete data was available of 421 participants and mean baseline CRP was 5.7 (5.5) mg/L with no significant differences across groups. While VO2 increased in a dose response manner, there were no significant changes in CRP in any of the exercise intervention groups compared to the control group. Change in fitness was not associated with change in CRP, whereas change in weight was significantly associated with change in CRP.
Conclusion
Despite increasing fitness, six months of aerobic exercise training did not improve CRP. However, improvements in CRP were associated with reductions in weight.
doi:10.1249/MSS.0b013e3181c03a2b
PMCID: PMC2891301  PMID: 19952829
exercise; inflammation; female; weight
13.  Effect of exercise training intensity on abdominal visceral fat and body composition 
The metabolic syndrome is a complex clustering of metabolic defects associated with physical inactivity, abdominal adiposity, and aging.
Purpose
To examine the effects of exercise training intensity on abdominal visceral fat (AVF) and body composition in obese women with the metabolic syndrome.
Methods
Twenty-seven middle-aged, obese women (mean ± SD; age: 51 ± 9 years and body mass index: 34 ± 6 kg/m2) with the metabolic syndrome completed one-of-three 16-week aerobic exercise interventions: (i) No Exercise Training (Control): Seven participants maintained their existing levels of physical activity, (ii) Low-Intensity Exercise Training (LIET): eleven participants exercised 5 days · week-1 at an intensity ≤ lactate threshold (LT) (iii) High-Intensity Exercise Training (HIET): nine participants exercised 3 days · week-1 at an intensity > LT and 2 days ·week-1 ≤ LT. Exercise time was adjusted to maintain caloric expenditure (400 kcal·session-1). Single-slice computed tomography scans obtained at the L4-L5 disc-space and mid-thigh were used to determine abdominal fat and thigh muscle cross-sectional areas. Percent body fat was assessed by air displacement plethysmography.
Results
HIET significantly reduced total abdominal fat (p<0.001), abdominal subcutaneous fat (p=0.034) and AVF (p=0.010). There were no significant changes observed in any of these parameters within the Control or LIET conditions.
Conclusions
The present data indicate that body composition changes are affected by intensity of exercise training with HIET more effective for reducing total abdominal fat, subcutaneous abdominal fat and AVF in obese women with the metabolic syndrome.
doi:10.1249/MSS.0b013e3181801d40
PMCID: PMC2730190  PMID: 18845966
Physical Activity; Weight Loss; Metabolic Syndrome; Diabetes; Cardiovascular; Human
14.  Comparison of effects of diet versus exercise weight loss regimens on LDL and HDL particle size in obese adults 
Background
Obesity is associated with an atherogenic lipid profile characterized by a predominance of small LDL and HDL particles. Weight loss, by dietary restriction or exercise, increases LDL particle size. Whether these interventions can augment HDL size in conjunction with LDL size remains unknown.
Objective
This study compared the effects of alternate day fasting (ADF), calorie restriction (CR), and endurance exercise on LDL and HDL particle size in overweight and obese subjects.
Methods
In a 12-week parallel-arm trial, adult subjects (n = 60) were randomized to 1 of 4 groups: 1) ADF (75% energy restriction for 24-h alternated with ad libitum feeding for 24-h), 2) CR (25% energy restriction every day), 3) exercise (moderate intensity training 3 x/week), or 4) control.
Results
Body weight was reduced (P < 0.001) by ADF, CR, and exercise (5.2 ± 1.1%, 5.0 ± 1.4%, 5.1 ± 0.9%, respectively). Plasma LDL cholesterol decreased (P < 0.05) with ADF (10 ± 4%) and CR (8 ± 4%), whereas HDL cholesterol increased (P < 0.05) with exercise (16 ± 5%). Integrated LDL particle size was augmented (P = 0.01) by ADF and CR. The proportion of small LDL particles decreased (P = 0.04) with ADF only, and the proportion of large HDL particles increased (P = 0.03) with exercise only.
Conclusion
These results indicate that dietary restriction increases LDL particle size, while endurance training augments HDL particle size, with minimal weight loss. None of these interventions concomitantly increased both LDL and HDL particle size, however.
doi:10.1186/1476-511X-10-119
PMCID: PMC3150311  PMID: 21767400
Calorie restriction; alternate day fasting; endurance exercise; weight loss; LDL particle size; HDL particle size; cholesterol; obese adults
15.  Little evidence of systemic and adipose tissue inflammation in overweight individuals† 
Context: The effect of weight loss by diet alone or diet in conjunction with exercise on low-grade inflammation in non-obese (overweight) individuals is not known. Objective: Test the hypothesis that 24 weeks of moderate calorie restriction (CR; 25%) by diet only or with aerobic exercise would reduce markers of systemic inflammation and attenuate inflammation gene expression in subcutaneous adipose tissue. Design: Randomized controlled trial. Setting: Institutional Research Center. Participants: Thirty-five overweight (body mass index: 27.8 ± 0.7 kg/m2) but otherwise healthy participants (16M/19F) completed the study. Intervention: Participants were randomized to either CR (25% reduction in energy intake, n = 12), caloric restriction + exercise (CR + EX: 12.5% reduction in energy intake + 12.5% increase in exercise energy expenditure, n = 12), or control (healthy weight-maintenance diet, n = 11) for 6 months. Main outcome measures: Fasting serum markers of inflammation [leptin, highly sensitive C-reactive protein (hsCRP), interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-α), adiponectin] and inflammation-related genes [CD68, IL-6, TNF-α, macrophage migration inhibitory factor (MIF), monocyte chemoattractant protein-1 (MCP-1), adiponectin, plasminogen activator inhibitor-1 (PAI-1)] in subcutaneous adipose tissue. Results: CR and CR + EX lost similar amounts of body weight (–10 ± 1%), fat mass (–24 ± 3%), visceral fat (–27 ± 3%), and had increased insulin sensitivity (CR: 40 ± 20%, CR + EX: 66 ± 22%). Leptin was significantly decreased from baseline (p < 0.001) in both groups however TNF-α and IL-6 were not changed. hsCRP was decreased in CR + EX. There was no change in the expression of genes involved in macrophage infiltration (CD68, MIF MCP-1, PAI-1) or inflammation (IL-6, TNF-α, adiponectin) in either CR or CR + EX. Conclusion: A 10% weight loss with a 25% CR diet alone or with exercise did not impact markers of systemic inflammation or the expression of inflammation-related adipose genes in overweight individuals.
doi:10.3389/fgene.2012.00058
PMCID: PMC3329711  PMID: 22529850
caloric restriction; inflammation; subcutaneous fat; exercise; aging; immune function
16.  Dietary Weight-Loss and Exercise Effects on Insulin Resistance in Postmenopausal Women 
Background
Comprehensive lifestyle interventions are effective in preventing diabetes and restoring glucose regulation; however, the key stimulus for change has not been identified and effects in older individuals are not established. The aim of the study was to investigate the independent and combined effects of dietary weight-loss and exercise on insulin sensitivity and restoration of normal fasting glucose in mid-aged and older women.
Design
Four-arm RCT, conducted between 2005 and 2009 and data analyzed in 2010.
Setting/participants
439 inactive, overweight/obese postmenopausal women. Interventions: Women were assigned to: dietary weight loss (n=118), exercise (n=117), exercise+diet (n=117), or control (n=87). The diet intervention was a group-based reduced-calorie program with a 10% weight-loss goal. The exercise intervention was 45 min/day, 5 days/week of moderate-to-vigorous intensity aerobic activity.
Main outcome measures
12-month change in serum insulin, C-peptide, fasting glucose, and whole body insulin resistance (HOMA-IR).
Results
A significant improvement in HOMA-IR was detected in the diet (−24%, p<0.001) and exercise+ diet (−26%, p<0.001) groups, but not in the exercise (−9%, p=0.22) group compared to controls (−2%); these effects were similar in middle-aged (50–60 years) and older women (aged 60–75 years). Among those with impaired fasting glucose (5.6–6.9 mmol/L) at baseline (n=143; 33%), the odds (95% CI) of regressing to normal fasting glucose after adjusting for weight loss and baseline levels were: 2.5 (0.8, 8.4), 2.76 (0.8, 10.0), and 3.1 (1.0, 9.9) in the diet, exercise+diet, and exercise group, respectively, compared to controls.
Conclusions
Dietary weight loss, with or without exercise, significantly improved insulin resistance. Older women derived as much benefit as did the younger postmenopausal women.
doi:10.1016/j.amepre.2011.06.042
PMCID: PMC3185302  PMID: 21961463
17.  Adiposity changes after a 1-year aerobic exercise intervention among postmenopausal women: a randomized controlled trial 
Objective:
We examined the effects of an aerobic exercise intervention on adiposity outcomes that may be involved in the association between physical activity and breast cancer risk.
Design:
This study was a two-centre, two-armed, randomized controlled trial. The 1-year-long exercise intervention included 45 min of moderate-to-vigorous aerobic exercise five times per week, with at least three of the sessions being facility based. The control group was asked not to change their activity and both groups were asked not to change their diet.
Subjects:
A total of 320 postmenopausal, sedentary, normal weight-to-obese women aged 50–74 years who were cancer-free, nondiabetic and nonhormone replacement therapy users were included in this study.
Measurements:
Anthropometric measurements of height, weight and waist and hip circumferences; dual energy X-ray absorptiometry measurements of total body fat; and computerized tomography measurements of abdominal adiposity were carried out.
Results:
Women in the exercise group exercised a mean of 3.6 days (s.d.=1.3) per week and 178.5 min (s.d.=76.1) per week. Changes in all measures of adiposity favored exercisers relative to controls (P<0.001). The mean difference between groups was: −1.8 kg for body weight; −2.0 kg for total body fat; −14.9 cm2 for intra-abdominal fat area; and −24.1 cm2 for subcutaneous abdominal fat area. A linear trend of greater body fat loss with increasing volume of exercise was also observed.
Conclusion:
A 1-year aerobic exercise program consistent with current public health guidelines resulted in reduced adiposity levels in previously sedentary postmenopausal women at higher risk of breast cancer.
doi:10.1038/ijo.2010.147
PMCID: PMC3061001  PMID: 20820172
clinical trial; exercise; body weight; breast neoplasms; biological mechanisms
18.  Weight Regain is Related to Decreases in Physical Activity During Weight Loss 
Purpose
To examine whether adaptations in physical activity energy expenditure (PAEE) and resting metabolic rate (RMR) during weight loss were associated with future weight regain in overweight/obese, older women.
Research Methods and Procedures
Thirty-four overweight/obese (BMI=25–40 kg/m2), postmenopausal women underwent a 20-week weight loss intervention of hypocaloric diet with (low- or high-intensity) or without treadmill walking (weekly caloric deficit was ~11760 kJ), with a subsequent 12-month follow-up. RMR (via indirect calorimetry), PAEE (by RT3 accelerometer) and body composition (by DXA) were measured before and after intervention. Body weight and self-reported information on physical activity were collected after intervention, and at 6- and 12-months following intervention.
Results
The intervention resulted in decreases in body weight, lean mass, fat mass, percent body fat, RMR, and PAEE (p < 0.001 for all). Weight regain was 2.9 ± 3.3 kg (−3.1 to +9.2 kg) at 6- months and 5.2 ± 5.0 kg (−2.3 to +21.7 kg) at 12-months following intervention. The amount of weight regained after 6- and 12-months was inversely associated with decreases in PAEE during the weight loss intervention (r= −0.521, p = 0.002 and r= −0.404, p = 0.018, respectively), such that women with larger declines in PAEE during weight loss experienced greater weight regain during follow-up. Weight regain was not associated with changes in RMR during intervention or with self-reported physical activity during follow-up.
Conclusion
This study demonstrates that, while both RMR and PAEE decreased during weight loss in postmenopausal women, maintaining high levels of daily physical activity during weight loss may be important to mitigate weight regain after weight loss.
doi:10.1249/MSS.0b013e31817d8176
PMCID: PMC2797708  PMID: 18799988
energy expenditure; resting metabolic rate; weight loss intervention; hypocaloric diet
19.  Addition of Aerobic Exercise to a Weight Loss Program Increases BMD, with an Associated Reduction in Inflammation in Overweight Postmenopausal Women 
Calcified tissue international  2009;84(4):257-265.
Increased inflammation and weight loss are associated with a reduction in bone mineral density (BMD). Aerobic exercise may minimize the loss of bone and weight loss may contribute to a decrease in cytokines. We tested the hypothesis that aerobic exercise in combination with a weight loss program would decrease circulating concentrations of inflammatory markers, thus mediating changes in BMD. This was a nonrandomized controlled trial. Eighty-six overweight and obese postmenopausal women (50–70 years of age; BMI, 25–40 kg/m2) participated in a weight loss (WL; n = 40) or weight loss plus walking (WL + AEX; n = 46) program. Outcome measures included BMD and bone mineral content of the femoral neck and lumbar spine measured by dual energy X-ray absorptiometry, interleukin-6, tumor necrosis factor-α, soluble receptors of IL-6, and TNF-α (sTNFR1 and sTNFR2; receptors in a subset of the population), VO2 max, fat mass, and lean mass. Weight decreased in the WL (p < 0.001) and WL + AEX (p < 0.001) groups. VO2 max increased (p < 0.001) after WL + AEX. There was a 2% increase in femoral neck BMD in the WL + AEX group (p = 0.001), which was significantly different from the WL group. The change in sTNFR1 was significantly associated with the change in femoral neck BMD (p < 0.05). The change in VO2 max was an independent predictor of the change in femoral neck BMD. Our findings suggest that the addition of aerobic exercise is recommended to decrease inflammation and increase BMD during weight loss in overweight postmenopausal women.
doi:10.1007/s00223-009-9232-z
PMCID: PMC2926800  PMID: 19280097
Aging; Cytokines; Inflammation; Exercise; Weight loss
20.  Randomised, controlled walking trials in postmenopausal women: the minimum dose to improve aerobic fitness? 
Background: The American College of Sports Medicine recommends 20–60 minutes of aerobic exercise three to five days a week at an intensity of 40/50–85% of maximal aerobic power (VO2MAX) reserve, expending a total of 700–2000 kcal (2.93–8.36 MJ) a week to improve aerobic power and body composition.
Objective: To ascertain the minimum effective dose of exercise.
Methods: Voluntary, healthy, non-obese, sedentary, postmenopausal women (n = 121), 48–63 years of age, were randomised to four low dose walking groups or a control group; 116 subjects completed the study. The exercise groups walked five days a week for 24 weeks with the following intensity (% of VO2MAX) and energy expenditure (kcal/week): group W1, 55%/1500 kcal; group W2, 45%/1500 kcal; group W3, 55%/1000 kcal; group W4, 45%/1000 kcal. VO2MAX was measured in a direct maximal treadmill test. Submaximal aerobic fitness was estimated as heart rates at submaximal work levels corresponding to 65% and 75% of the baseline VO2MAX. The body mass index (BMI) was calculated and percentage of body fat (F%) estimated from skinfolds.
Results: The net change (the differences between changes in each exercise group and the control group) in VO2MAX was 2.9 ml/min/kg (95% confidence interval (CI) 1.5 to 4.2) in group W1, 2.6 ml/min/kg (95% CI 1.3 to 4.0) in group W2, 2.4 ml/min/kg (95% CI 0.9 to 3.8) in group W3, and 2.2 ml/min/kg (95% CI 0.8 to 3.5) in group W4. The heart rates in standard submaximal work decreased 4 to 8 beats/min in all the groups. There was no change in BMI, but the F% decreased by about 1% unit in all the groups.
Conclusions: Walking (for 24 weeks) at moderate intensity 45% to 55% of VO2MAX, with a total weekly energy expenditure of 1000–1500 kcal, improves VO2MAX and body composition of previously sedentary, non-obese, postmenopausal women. This dose of exercise apparently approaches the minimum effective dose.
doi:10.1136/bjsm.36.3.189
PMCID: PMC1724503  PMID: 12055113
21.  Effects of caloric restriction with varying energy density and aerobic exercise on weight change and satiety in young female adults 
Nutrition Research and Practice  2010;4(5):414-420.
This study examines the combined effects of caloric restriction on body composition, blood lipid, and satiety in slightly overweight women by varying food density and aerobic exercise. Twenty-three women were randomly assigned to one of two groups for a four-week weight management program: the high-energy density diet plus exercise (HDE: n = 12, 22 ± 2 yrs, 65 ± 7 kg, 164 ± 5 cm, 35 ± 4 % fat) and low-energy density diet plus exercise (LDE: n = 11, 22 ± 1 yrs, 67 ± 7 kg, 161 ± 2 cm, 35 ± 4 % fat) groups. Subjects maintained a low-calorie diet (1,500 kcal/day) during the program. Isocaloric (483 ± 26 for HDE, 487 ± 27 kcal for LDE) but different weight (365 ± 68 for HDE, 814 ± 202 g for LDE) of lunch was provided. After lunch, they biked at 60% of maximum capacity for 40 minutes, five times per week. The hunger level was scaled (1: extremely hungry; 9: extremely full) at 17:30 each day. Before and after the program, the subjects' physical characteristics were measured, and fasting blood samples were drawn. The daily energy intake was 1,551 ± 259 for HDE and 1,404 ± 150 kcal for LDE (P > 0.05). After four weeks, the subjects' weights and % fat decreased for both LDE (-1.9 kg and -1.5%, P < 0.05) and HDE (-1.6 kg and -1.4%, respectively, P < 0.05). The hunger level was significantly higher for HDE (2.46 ± 0.28) than for LDE (3.10 ± 0.26) (P < 0.05). The results suggest that a low-energy density diet is more likely to be tolerated than a high-energy density diet for a weight management program combining a low-calorie diet and exercise, mainly because of a reduced hunger sensation.
doi:10.4162/nrp.2010.4.5.414
PMCID: PMC2981725  PMID: 21103088
Low calorie diet; weight management; energy density; satiety
22.  Weight Bias and Weight Loss Treatment Outcomes in Treatment-Seeking Adults 
Background
Few studies have explored the relationship between weight bias and weight loss treatment outcomes.
Purpose
This investigation examined the relationship between implicit and explicit weight bias and (a) program attrition, (b) weight loss, (c) self-monitoring adherence, (d) daily exercise levels and overall caloric expenditure, (e) daily caloric intake, and (f) daily caloric deficit among overweight/obese treatment-seeking adults.
Methods
Forty-six overweight/obese adults (body mass index≥27 kg/m2) participating in an 18-week, stepped-care, behavioral weight loss program completed implicit and explicit measures of weight bias. Participants were instructed to self-monitor and electronically report daily energy intake, exercise, and energy expenditure.
Results
Greater weight bias was associated with inconsistent self-monitoring, greater caloric intake, lower energy expenditure and exercise, creation of a smaller caloric deficit, higher program attrition, as well as less weight loss during the self-help phase of the stepped-care treatment.
Conclusions
Weight bias may interfere with overweight/obese treatment-seeking adults' ability to achieve optimal health.
doi:10.1007/s12160-009-9109-4
PMCID: PMC3538814  PMID: 19548044
Weight loss; Obesity; Stigma; Self-monitoring; Exercise; Caloric intake
23.  The effect of 12 weeks of aerobic, resistance or combination exercise training on cardiovascular risk factors in the overweight and obese in a randomized trial 
BMC Public Health  2012;12:704.
Background
Evidence suggests that exercise training improves CVD risk factors. However, it is unclear whether health benefits are limited to aerobic training or if other exercise modalities such as resistance training or a combination are as effective or more effective in the overweight and obese. The aim of this study is to investigate whether 12 weeks of moderate-intensity aerobic, resistance, or combined exercise training would induce and sustain improvements in cardiovascular risk profile, weight and fat loss in overweight and obese adults compared to no exercise.
Methods
Twelve-week randomized parallel design examining the effects of different exercise regimes on fasting measures of lipids, glucose and insulin and changes in body weight, fat mass and dietary intake. Participants were randomized to either: Group 1 (Control, n = 16); Group 2 (Aerobic, n = 15); Group 3 (Resistance, n = 16); Group 4 (Combination, n = 17). Data was analysed using General Linear Model to assess the effects of the groups after adjusting for baseline values. Within-group data was analyzed with the paired t-test and between-group effects using post hoc comparisons.
Results
Significant improvements in body weight (−1.6%, p = 0.044) for the Combination group compared to Control and Resistance groups and total body fat compared to Control (−4.4%, p = 0.003) and Resistance (−3%, p = 0.041). Significant improvements in body fat percentage (−2.6%, p = 0.008), abdominal fat percentage (−2.8%, p = 0.034) and cardio-respiratory fitness (13.3%, p = 0.006) were seen in the Combination group compared to Control. Levels of ApoB48 were 32% lower in the Resistance group compared to Control (p = 0.04).
Conclusion
A 12-week training program comprising of resistance or combination exercise, at moderate-intensity for 30 min, five days/week resulted in improvements in the cardiovascular risk profile in overweight and obese participants compared to no exercise. From our observations, combination exercise gave greater benefits for weight loss, fat loss and cardio-respiratory fitness than aerobic and resistance training modalities. Therefore, combination exercise training should be recommended for overweight and obese adults in National Physical Activity Guidelines.
This clinical trial was registered with the Australian New Zealand Clinical Trials Registry (ANZCTR), registration number: ACTRN12609000684224.
doi:10.1186/1471-2458-12-704
PMCID: PMC3487794  PMID: 23006411
Obesity; Overweight; Cardiovascular risk factors; Exercise training
24.  Effects of ground and joint reaction force exercise on lumbar spine and femoral neck bone mineral density in postmenopausal women: a meta-analysis of randomized controlled trials 
Background
Low bone mineral density (BMD) and subsequent fractures are a major public health problem in postmenopausal women. The purpose of this study was to use the aggregate data meta-analytic approach to examine the effects of ground (for example, walking) and/or joint reaction (for example, strength training) exercise on femoral neck (FN) and lumbar spine (LS) BMD in postmenopausal women.
Methods
The a priori inclusion criteria were: (1) randomized controlled trials, (2) exercise intervention ≥ 24 weeks, (3) comparative control group, (4) postmenopausal women, (5) participants not regularly active, i.e., less than 150 minutes of moderate intensity (3.0 to 5.9 metabolic equivalents) weight bearing endurance activity per week, less than 75 minutes of vigorous intensity (> 6.0 metabolic equivalents) weight bearing endurance activity per week, resistance training < 2 times per week, (6) published and unpublished studies in any language since January 1, 1989, (7) BMD data available at the FN and/or LS. Studies were located by searching six electronic databases, cross-referencing, hand searching and expert review. Dual selection of studies and data abstraction were performed. Hedge’s standardized effect size (g) was calculated for each FN and LS BMD result and pooled using random-effects models. Z-score alpha values, 95%confidence intervals (CI) and number-needed-to-treat (NNT) were calculated for pooled results. Heterogeneity was examined using Q and I2. Mixed-effects ANOVA and simple meta-regression were used to examine changes in FN and LS BMD according to selected categorical and continuous variables. Statistical significance was set at an alpha value ≤0.05 and a trend at >0.05 to ≤ 0.10.
Results
Small, statistically significant exercise minus control group improvements were found for both FN (28 g’s, 1632 participants, g = 0.288, 95% CI = 0.102, 0.474, p = 0.002, Q = 90.5, p < 0.0001, I2 = 70.1%, NNT = 6) and LS (28 g’s, 1504 participants, g = 0.179, 95% CI = −0.003, 0.361, p = 0.05, Q = 77.7, p < 0.0001, I2 = 65.3%, NNT = 6) BMD. Clinically, it was estimated that the overall changes in FN and LS would reduce the 20-year relative risk of osteoporotic fracture at any site by approximately 11% and 10%, respectively. None of the mixed-effects ANOVA analyses were statistically significant. Statistically significant, or a trend for statistically significant, associations were observed for changes in FN and LS BMD and 20 different predictors.
Conclusions
The overall findings suggest that exercise may result in clinically relevant benefits to FN and LS BMD in postmenopausal women. Several of the observed associations appear worthy of further investigation in well-designed randomized controlled trials.
doi:10.1186/1471-2474-13-177
PMCID: PMC3489866  PMID: 22992273
Exercise; Bone; Osteoporosis; Women; Postmenopausal; Aging; Meta-analysis; Systematic review
25.  Low Calorie Dieting Increases Cortisol 
Psychosomatic medicine  2010;72(4):357-364.
Objective
Prior research has demonstrated that dieting, or the restriction of caloric intake, does not lead to long-term weight loss. This study tested the hypothesis that dieting is ineffective because it increases chronic psychological stress and cortisol production – two factors that are known to cause weight gain. Further, this study examined the respective roles of the two main behaviors that comprise dieting – monitoring one’s caloric intake and restricting one’s caloric intake – on psychological and biological stress indicators.
Methods
In a 2 (monitoring vs. not) × 2 (restricting vs. not) fully crossed, controlled experiment, 121 female participants were randomly assigned to one of four dietary interventions for three weeks. The monitoring + restricting condition tracked their caloric intake and restricted their caloric intake (1200 kcal/day); the monitoring only condition tracked their caloric intake but ate normally; the restricting only condition was provided 1200 kcal/day of food but did not track their calories, and the control group ate normally and did not track their intake. Before and after the interventions, participants completed measures of perceived stress and two days of diurnal saliva sampling to test for cortisol.
Results
Restricting calories increased the total output of cortisol, and monitoring calories increased perceived stress.
Conclusions
Dieting may be deleterious to psychological well-being and biological functioning, and changes in clinical recommendations may be in order.
doi:10.1097/PSY.0b013e3181d9523c
PMCID: PMC2895000  PMID: 20368473
Dieting; stress; cortisol

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