Publications by authors named "Sylvia Santosa"

32 Publications

Putting ATM to BED: How Adipose Tissue Macrophages Are Affected by Bariatric Surgery, Exercise, and Dietary Fatty Acids.

Adv Nutr 2021 May 12. Epub 2021 May 12.

Department of Health, Kinesiology, and Applied Physiology, Concordia University, Montreal, Quebec, Canada.

With increasing adiposity in obesity, adipose tissue macrophages contribute to adipose tissue malfunction and increased circulating proinflammatory cytokines. The chronic low-grade inflammation that occurs in obesity ultimately gives rise to a state of metainflammation that increases the risk of metabolic disease. To date, only lifestyle and surgical interventions have been shown to be somewhat effective at reversing the negative consequences of obesity and restoring adipose tissue homeostasis. Exercise, dietary interventions, and bariatric surgery result in immunomodulation, and for some individuals their effects are significant with or without weight loss. Robust evidence suggests that these interventions reduce chronic inflammation, in part, by affecting macrophage infiltration and promoting a phenotypic switch from the M1- to M2-like macrophages. The purpose of this review is to discuss the impact of dietary fatty acids, exercise, and bariatric surgery on cellular characteristics affecting adipose tissue macrophage presence and phenotypes in obesity.
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http://dx.doi.org/10.1093/advances/nmab011DOI Listing
May 2021

Substrate Oxidation Is Altered by Obesity During Submaximal Cycling in Prepubertal and Early Pubertal Children: A Quality Study.

Pediatr Exerc Sci 2021 03 14;33(1):32-39. Epub 2021 Mar 14.

Sainte-Justine University Hospital Research Center.

Background: To examine substrate oxidation in prepubertal and early pubertal children as a function of body weight, body composition, and sex during an exhaustive cycling test.

Methods: This study included 320 children in prepubertal and early puberty (Tanner stage 1 or 2; n = 188 males) who completed a minimum of 4 stages (2-5 min/stage) of an adapted version of the McMaster exhaustive exercise protocol on an upright cycle ergometer. Substrate utilization, relative to individual VO2peak, was determined using VO2 and VCO2 data, obtained with breath-by-breath gas analysis during exercise.

Results: Both peak (mg/kg lean body mass·min) and submaximal lipid oxidation (mg/kg lean body mass·min) were highest (P < .01) in children with healthy weight (HW), then overweight, and lowest in obese (OB). Both females with HW (compared with males with HW) and females with OB (compared with males with OB) had higher (P < .01) peak and submaximal lipid oxidation. In children with OB, fat-free mass correlated positively (P < .01) with submaximal lipid oxidation (r = .50). In contrast, in children with HW and overweight, fat-free mass correlated positively (P < .01) with carbohydrate oxidation (r = .52 and r = .47, respectively).

Conclusion: Obesity during childhood may alter substrate oxidation during exercise. These results may have implications in the implementation of exercise programs in prepubertal or early puberty to control adiposity.
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http://dx.doi.org/10.1123/pes.2020-0059DOI Listing
March 2021

Association between rs174537 polymorphism and immune cell profiles in abdominal and femoral subcutaneous adipose tissue: an exploratory study in adults with obesity.

Adipocyte 2021 12;10(1):124-130

Department of Health, Kinesiology and Applied Physiology, Concordia University , Montreal, Canada.

Fatty acid desaturase 1 () polymorphisms alter fatty acid content in subcutaneous adipose tissue (SAT); however, existing evidence is limited and conflicting regarding the association between variants and SAT inflammatory status. To advance this area, we conducted an exploratory study to investigate whether the common rs174537 polymorphism in was associated with immune cell profiles in abdominal and femoral SAT in individuals with obesity. gene expression and immune cell profiles in SAT depots were assessed by qPCR and flow cytometry, respectively. Although gene expression was associated with genotype, no associations were observed with immune cell profiles in either depot. Our study provides additional evidence that rs174537 in has minimal impact on inflammatory status in obese SAT.
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http://dx.doi.org/10.1080/21623945.2021.1888470DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7894460PMC
December 2021

Sex Affects Regional Variations in Subcutaneous Adipose Tissue T Cells but not Macrophages in Adults with Obesity.

Obesity (Silver Spring) 2020 12 11;28(12):2310-2314. Epub 2020 Nov 11.

Department of Health, Kinesiology, and Applied Physiology, Concordia University, Montreal, Quebec, Canada.

Objective: The inflammatory environment in lower-body subcutaneous adipose tissue (SAT) has been largely unexplored. This study aimed to examine the effects of region (upper body vs. lower body) and sex on SAT immune cell profiles in young adults with obesity.

Methods: Abdominal (AB) and femoral (FEM) SAT was collected from 12 males (mean [SEM] age = 30.8 [1.4] years; mean [SEM] BMI = 34.1 [1.1] kg/m ) and 22 females (mean [SEM] age = 30.6 [0.6] years; mean [SEM] BMI = 34.0 [0.7] kg/m ) with obesity via needle aspiration. Flow cytometry was used to quantify macrophage (CD68+) and T-cell (CD3+) subpopulations in the stromovascular fraction of each SAT region.

Results: Females had a greater proportion of most T-cell types (CD3+CD4+CD45RA+, CD3+CD4+CD45RA-, and CD3+CD8+CD45RA+) in FEM compared with AB SAT, while males had similar proportions in both regions. Regardless of sex, the M1-like macrophage population (CD68+CD206-) was proportionally higher in AB SAT than in FEM SAT.

Conclusions: Results showed that T-cell populations vary by SAT region in females but not males. Both sexes, however, have proportionately more proinflammatory macrophages in upper-body than in lower-body SAT. It remains to be seen how these unique immune cell profiles in males and females with obesity contribute to adipose tissue inflammation and metabolic disease risk.
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http://dx.doi.org/10.1002/oby.23039DOI Listing
December 2020

Methodological considerations for the measurement of arterial stiffness using applanation tonometry.

J Hypertens 2021 Mar;39(3):428-436

Division of Experimental Medicine, Department of Medicine, McGill University.

Introduction: Accurate comparisons of carotid--femoral pulse wave velocity (cfPWV) within and across studies require standardized procedures. Guidelines suggest reporting the average of at least two cfPWV measurements; if the difference exceeds 0.5 m/s, a third measurement should be taken, and the median reported. Another method involves repeating measurements until two values are within 0.5 m/s. However, in many studies, duplicate measurements are averaged irrespective of the difference between readings. We evaluated the impact of these methods on the reported cfPWV value.

Methods: Measurements of cfPWV (SphygmoCor) from five studies included individuals spanning a wide age range, with or without comorbid conditions, and pregnant women. In participants with at least three high-quality measurements, differences between the median value (MED) and the average of the first two cfPWV measurements (AVG1) and the average of two cfPWV measurements within 0.5 m/s (AVG2) were evaluated using paired t-tests and Bland--Altman plots.

Results: Participants' mean age was 50 ± 14 years and BMI was 28.0 ± 5.5 kg/m2 (N = 306, 79% women). The overall mean difference was -0.10 m/s (95% CI 0.17 to -0.04) between MED and AVG1, and 0.11 m/s (95% CI 0.05--0.17) between MED and AVG2. The absolute difference exceeded 0.5 m/s in 34% (MED-AVG1) and 22% (MED-AVG2) of participants, and 1 m/s in 8% of participants (both MED-AVG1 and MED-AVG2). Scatter around the bias line increased with higher mean cfPWV values.

Conclusion: Although the overall mean difference in cfPWV between protocols was not clinically relevant, large variation led to absolute differences exceeding 0.5 m/s in a large proportion of participants.
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http://dx.doi.org/10.1097/HJH.0000000000002665DOI Listing
March 2021

A reliable, reproducible flow cytometry protocol for immune cell quantification in human adipose tissue.

Anal Biochem 2021 01 11;613:113951. Epub 2020 Sep 11.

Department of Health, Kinesiology, and Applied Physiology, Concordia University, 7141 Sherbrooke St W, Montreal, QC, H4B 1R6, Canada; Metabolism, Obesity, Nutrition Lab, PERFORM Centre, Concordia University, 7200 Sherbrooke St W, Montreal, QC, H4B 1R6, Canada; Centre de Recherche - Axe Maladies Chroniques, Centre Intégré Universitaire de Santé et de Services Sociaux Du Nord-de-l'Ile-de-Montreal, Hôpital Du Sacré-Coeur de Montreal, 5400 Boul Gouin O, Montréal, QC, H4J 1C5, Canada. Electronic address:

The ability to accurately identify and quantify immune cell populations within adipose tissue is important in understanding the role of immune cells in metabolic disease risk. Flow cytometry is the gold standard method for immune cell quantification. However, quantification of immune cells from adipose tissue presents a number of challenges because of the complexities of working with an oily substance and the rapid deterioration of immune cell viability before analysis can be performed. Here we present a highly reproducible flow cytometry protocol for the quantification of immune cells in human adipose tissue, which overcomes these issues.
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http://dx.doi.org/10.1016/j.ab.2020.113951DOI Listing
January 2021

Acetyl-CoA Regulation, OXPHOS Integrity and Leptin Levels Are Different in Females With Childhood vs Adulthood Onset of Obesity.

Endocrinology 2020 11;161(11)

Department of Health, Kinesiology, and Applied Physiology, Concordia University, Montreal, Quebec, Canada.

Although childhood-onset obesity (CO) and adulthood-onset obesity (AO) are known to lead to distinctive clinical manifestations and disease risks, the fundamental differences between them are largely unclear. The aim of the current study is to investigate the fundamental differences between subcutaneous adipose tissue from CO and AO and to identify metabolic differences between abdominal (abSAT) and femoral subcutaneous adipose tissues (feSAT). Total and regional body composition was assessed using dual-energy x-ray absorptiometry (DXA) and computed tomography. Levels of acetyl-CoA, NAD+/NADH, acetyl-CoA network genes, mitochondrial complex abundance, H3 acetylation were determined in biopsied abSAT and feSAT. Serum leptin and adiponectin were measured. Our results showed that acetyl-CoA was higher in subcutaneous adipose tissue from subjects with AO compared with CO. Multiple linear regression revealed that ATP citrate lyase was the only main effect affecting the level of acetyl-CoA. Circulating leptin concentrations was higher in AO. The increased level of acetyl-CoA was strongly associated with histone H3 acetylation, LEP expression in adipose tissue, and circulating leptin in AO. NAD+/NADH was higher in CO; however, abundance of mitochondrial complexes, the complex II:complex V ratio, and the complex IV:complex V ratio were lower in CO, reflecting compromised mitochondrial function in subcutaneous adipose tissue from CO. Moreover, we identified differences in the level of acetyl-CoA and NAD+/NADH ratio between abSAT and feSAT, suggesting that these fat depots may possess different metabolic properties. The fundamental difference in the important metabolic intermediate acetyl-CoA between CO and AO may help us better understand the development of obesity and the pathogenesis of different obesity-related diseases in humans.
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http://dx.doi.org/10.1210/endocr/bqaa142DOI Listing
November 2020

Obesity and ageing: Two sides of the same coin.

Obes Rev 2020 04 5;21(4):e12991. Epub 2020 Feb 5.

Department of Health, Kinesiology, and Applied Physiology, Concordia University, Quebec, Montreal, Canada.

Conditions and comorbidities of obesity mirror those of ageing and age-related diseases. Obesity and ageing share a similar spectrum of phenotypes such as compromised genomic integrity, impaired mitochondrial function, accumulation of intracellular macromolecules, weakened immunity, shifts in tissue and body composition, and enhanced systemic inflammation. Moreover, it has been shown that obesity reduces life expectancy by 5.8 years in men and 7.1 years in women after the age of 40. Shorter life expectancy could be because obesity holistically accelerates ageing at multiple levels. Besides jeopardizing nuclear DNA and mitochondrial DNA integrity, obesity modifies the DNA methylation pattern, which is associated with epigenetic ageing in different tissues. Additionally, other signs of ageing are seen in individuals with obesity including telomere shortening, systemic inflammation, and functional declines. This review aims to show how obesity and ageing are "two sides of the same coin" through discussing how obesity predisposes an individual to age-related conditions, illness, and disease. We will further demonstrate how the mechanisms that perpetuate the early-onset of chronic diseases in obesity parallel those of ageing.
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http://dx.doi.org/10.1111/obr.12991DOI Listing
April 2020

Intra-Abdominal Adipose Tissue Quantification by Alternative Versus Reference Methods: A Systematic Review and Meta-Analysis.

Obesity (Silver Spring) 2019 07 27;27(7):1115-1122. Epub 2019 May 27.

Department of Health, Kinesiology and Applied Physiology, Concordia University, Montreal, Quebec, Canada.

Objective: This meta-analysis aimed to assess the agreement between intra-abdominal adipose tissue (IAAT) quantified by alternative methods and the reference standards, computed tomography (CT) and magnetic resonance imaging (MRI).

Methods: MEDLINE and EMBASE electronic databases were systematically searched to identify studies that quantified IAAT thickness, area, or volume by a comparator method and CT or MRI. Using an inverse variance weighted approach (random-effects model), the mean differences and 95% limits of agreement (LoA) were pooled between methods.

Results: The meta-analysis included 24 studies using four comparator methods. The pooled mean differences were -0.3 cm (95% LoA: -3.4 to 3.2 cm; P = 0.400) for ultrasound and -11.6 cm (95% LoA: -43.1 to 19.9 cm ; P = 0.004) for bioelectrical impedance analysis. Dual-energy x-ray absorptiometry (DXA) quantified both IAAT area and volume with mean differences of 8.1 cm (95% LoA: -98.9 to 115.1 cm ; P = 0.061) and 10 cm (95% LoA: -280 to 300 cm ; P = 0.808), respectively.

Conclusions: Ultrasound and DXA measure IAAT with minimal bias from CT or MRI, while bioelectrical impedance analysis systematically underestimates IAAT. However, with the exception of DXA for IAAT volume, the wide LoA caution against clinical or research use of the comparator methods and emphasize the need to optimize alternatives to the reference standards.
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http://dx.doi.org/10.1002/oby.22494DOI Listing
July 2019

Meeting fruit and vegetable consumption and physical activity recommendations among adolescents intending to lose weight.

Prev Med Rep 2019 Mar 28;13:11-15. Epub 2018 Oct 28.

Division of Nutrition, Physical Activity, and Obesity, National Center for Chronic Disease Prevention and Health Promotion, Centers for Disease Control and Prevention, Atlanta, GA, USA.

Two-thirds of adolescents who are overweight or have obesity report weight loss intentions. Most report using weight loss strategies consistent with expert recommendations for obesity prevention; however whether they meet recommended fruit and vegetable (F&V) intake and physical activity (PA) recommendations is unknown. We investigated whether weight loss attempts, and weight loss strategies were associated with meeting F&V and PA recommendations. Data were from the 2010 National Youth Physical Activity and Nutrition Study, which surveyed a cross-sectional, nationally representative sample of U.S. high school students. Analyses were restricted to overweight/obese students ( = 2841). Adjusted logistic regression models assessed the odds of meeting daily F&V and weekly PA recommendations after adjusting for grade, sex, race/ethnicity and perceived weight status. Compared to students who were overweight and were not currently intending to lose weight, students who were overweight and intending to lose weight were not more likely to meet F&V or PA. Among students with obesity, those who intended to lose weight were more likely than students who were not currently intending to lose weight to meet F&V recommendations (OR: 3.62, 95% CI: 1.70-7.73). Students who were overweight/obese and used F&V or PA for weight loss were significantly more likely to meet the corresponding recommendation than students intending to lose weight without specific strategies. Weight loss attempts alone do not affect the likelihood of meeting most expert recommendations. Public health efforts emphasizing recommended strategies for healthy eating and active living still need to be encouraged for overweight/obese youth.
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http://dx.doi.org/10.1016/j.pmedr.2018.10.021DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6240641PMC
March 2019

Regional adiposity and markers of inflammation in pre-school age children.

Sci Rep 2018 10 12;8(1):15204. Epub 2018 Oct 12.

Department of Health, Kinesiology, and Applied Physiology, Concordia University, Montreal, Quebec, Canada.

In adults, upper body fat partially increases metabolic disease risk through increasing systemic inflammation. Our objective was to determine if this relationship exists in preschool-aged children. A subset of children (n = 71, 35 males), 3.7 ± 1.0 y, were studied from n = 515 children recruited from randomly selected daycares in Montréal, QC. According to WHO charts for 2-5 y, 49 children were healthy weight (HW) and 21 were overweight (OW). Adiposity was determined through dual-energy x-ray absorptiometry. Blood concentrations of C-reactive protein (CRP) and tumour necrosis factor alpha (TNFα) were determined via enzyme-linked immunosorbent and multiplex assays, respectively. OW children had higher (p = 0.03) android:gynoid ratio 0.50 ± 0.09 compared to HW children 0.56 ± 0.12, indicating excess fat was predominantly stored in the abdominal depot. CRP was higher (p = 0.01) in OW children 1.45 ± 2.02 mg/L compared to HW 0.74 ± 1.38 mg/L. Percent fat was correlated with CRP (r = 0.32; p < 0.01) and TNFα (r = 0.25; p = 0.04) concentrations. CRP also correlated with android adiposity (r = 0.24; p = 0.04) and TNFα correlated with gynoid adiposity (r = 0.24; p = 0.04). We observed that greater adiposity is associated with higher systemic inflammation in pre-school aged children. Future longitudinal studies are needed to understand the long term consequences of excess total and regional body fat in young children.
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http://dx.doi.org/10.1038/s41598-018-33054-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6185945PMC
October 2018

Acute Testosterone Deficiency Alters Adipose Tissue Fatty Acid Storage.

J Clin Endocrinol Metab 2017 08;102(8):3056-3064

Endocrine Research Unit, Mayo Clinic, Rochester, Minnesota 55905.

Context: Although the long-term effects of testosterone on adipose tissue lipid metabolism in men have been defined, the short-term regulation of these effects is not well understood.

Objective: We examined the effects of acute testosterone withdrawal on subcutaneous abdominal and femoral adipose tissue fatty acid (FA) storage and cellular mechanisms.

Design: This was a prospective, randomized trial.

Setting: Mayo Clinic Clinical Research Unit.

Patients Or Participants: Thirty-two male volunteers ages 18 to 50 participated in these studies.

Interventions: Volunteers were randomized to receive (1) no treatment (control), (2) injections (7.5 mg) of Lupron®, or (3) Lupron and testosterone (L+T) replacement for 49 days, resulting in 4 weeks of sex steroid suppression in the Lupron group.

Main Outcome Measures: We measured body composition, fat cell size, adipose tissue meal FA and direct free FA storage, lipoprotein lipase (LPL), acyl coenzyme A synthetase (ACS), diacylglycerol acyltransferase activities, and CD36 content.

Results: Compared with control and L+T groups, acute testosterone deficiency resulted in greater femoral adipose tissue meal FA storage rates, fasting and fed LPL activity, and ACS activity.

Conclusions: These results suggest that in men, testosterone plays a tonic role in restraining FA storage in femoral adipose tissue via suppression of LPL and ACS activities. FA storage mechanisms in men appear sensitive to short-term changes in testosterone concentrations.
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http://dx.doi.org/10.1210/jc.2017-00757DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5546853PMC
August 2017

Factors associated with adipocyte size reduction after weight loss interventions for overweight and obesity: a systematic review and meta-regression.

Metabolism 2017 Feb 1;67:31-40. Epub 2016 Oct 1.

Department of Exercise Science, Concordia University, 7141 Sherbrooke St. W., Montreal, Quebec, Canada, H4B 1R6; Nutrition, Obesity and Metabolism Laboratory, PERFORM Centre, Concordia University, 7200 Sherbrooke St. W., Montreal, Quebec, Canada, H4B 1R6; Centre de Recherche - Axe Maladies Chroniques, Centre Intégré Universitaire de Santé et de Services Sociaux du Nord-de-l'Ile-de-Montréal, Hôpital du Sacré-Coeur de Montréal, 5400 Gouin Blvd. W., Montreal, Quebec, Canada, H4J 1C5. Electronic address:

Aims: Enlarged adipocytes are a prime feature of adipose tissue dysfunction, and may be an appropriate target to decrease disease risk in obesity. We aimed to assess the change in adipocyte size in response to lifestyle and surgical weight loss interventions for overweight or obesity; and to explore whether certain participant and intervention characteristics influence this response.

Methods: We systematically searched MEDLINE, EMBASE, CINAHL and Cochrane electronic databases to identify weight loss studies that quantified adipocyte size before and after the intervention. Using meta-regression analysis, we assessed the independent effects of weight loss, age, sex, adipocyte region, and intervention type (surgical vs. lifestyle) on adipocyte size reduction. We repeated the model as a sensitivity analysis including only the lifestyle interventions.

Results: Thirty-five studies met our eligibility criteria. In our main model, every 1.0% weight loss was associated with a 0.64% reduction in adipocyte size (p=0.003); and adipocytes from the upper body decreased 5% more in size than those in the lower body (p=0.009). These relationships were no longer significant when focusing only on lifestyle interventions. Moreover, age, sex and intervention type did not independently affect adipocyte size reduction in either model.

Conclusions: Weight loss in obese individuals is consistently associated with a decrease in adipocyte size that is more pronounced in upper-body adipocytes. It remains to be clarified how biological differences and intervention characteristics influence this relationship, and whether it corresponds with reductions in other aspects of adipose tissue dysfunction and disease risk.
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http://dx.doi.org/10.1016/j.metabol.2016.09.009DOI Listing
February 2017

Conjugated linoleic acid mitigates testosterone-related changes in body composition in male guinea pigs.

Nutr Res 2016 May 6;36(5):408-17. Epub 2016 Jan 6.

Department of Exercise Science, Concordia University, Montreal, QC H4B 1R6, Canada; Nutrition, Obesity and Metabolism Lab, PERFORM Centre, Concordia University, Montreal, QC H4B 1R6, Canada. Electronic address:

We hypothesize that conjugated linoleic acid (CLA) may be effective in preventing the changes in total and regional body composition and increases in interleukin (IL) 6 that occur as a result of hypogonadism. Male guinea pigs (n = 40, 70- to 72-week retired breeders) were block randomized by weight into 4 groups: (1) sham surgery (SHAM)/control (CTRL) diet, (2) SHAM/conjugated linoleic acid (CLA) diet (1%), (3) orchidectomy (ORX)/CTRL diet, and (4) ORX/CLA diet. Dual-energy x-ray absorptiometry scans were performed at baseline and week 16 to assess body composition. Serum IL-6 was analyzed using an enzyme-linked immune sorbent assay. Fatty acids (FAs) from visceral and subcutaneous adipose tissue were analyzed using gas chromatography. In ORX/CTRL guinea pigs, percent total body fat increased by 6.1%, and percent lean mass decreased by 6.7% over the 16-week treatment period, whereas no changes were observed for either parameter in ORX/CLA guinea pigs. Guinea pigs fed the CLA diet gained less percent total, upper, and lower body fat than those fed the CTRL diet regardless of surgical treatment. Regional adipose tissue FA composition was reflective of dietary FAs. Serum IL-6 concentrations were not different among groups. In this study, we observed that, in male guinea pigs, hypogonadism resulted in increased fat mass and decreased lean mass. In addition, CLA was effective in reducing gains in body fat and maintaining lean mass in both hypogonadal and intact guinea pigs.
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http://dx.doi.org/10.1016/j.nutres.2015.12.013DOI Listing
May 2016

Acute Female Hypogonadism Alters Adipose Tissue Fatty Acid Storage Factors and Chylomicronemia.

J Clin Endocrinol Metab 2016 05 22;101(5):2089-98. Epub 2016 Mar 22.

Endocrine Research Unit (S.S., M.D.J.), and Department of General Internal Medicine (S.L.B.), Mayo Clinic, Rochester, Minnesota 55905; and Department of Exercise Science (S.S.), and PERFORM Centre (S.S.) Concordia University, Montréal, Québec, Canada H4B 1R6.

Context: Chronic sex steroid deficiency has effects on adipose fatty acid (FA) storage mechanisms and fat oxidation, but the chronology of events are not well understood.

Objective: The objective of the study was to examine the acute effects of female sex steroid suppression on cellular mechanisms affecting abdominal and femoral subcutaneous adipose tissue FA storage.

Design: This study had a randomized, longitudinal, parallel study design.

Setting: The study was conducted at the Mayo Clinic Clinical Research Unit.

Participants: Thirty-eight nonsmoking premenopausal women aged 18-50 years participated in the study.

Intervention: The intervention included randomization to receive one of the following: 1) no treatment (control), 2) 3.75 mg of Lupron, or 3) 3.75 mg of Lupron and estrogen, but not progesterone, replacement for 49 days, resulting in at least 4 weeks of sex steroid suppression.

Main Outcome Measures: Body composition, fat cell size, postprandial chylomicron and nonchylomicron triglyceride concentrations, adipose tissue meal FA storage, direct free fatty acid storage, lipoprotein lipase, acyl CoA synthetase, and diacylglycerol acyltransferase activities, and CD36 content were measured.

Results: Compared with the control group, the fed state femoral lipoprotein lipase activity was reduced in women taking Lupron and those taking Lupron and estrogen replacement. In addition, we observed significantly greater postprandial chylomicronemia in the Lupron group than in the other two groups. There were no differences in overall fat storage and oxidation. Depending on the mode of data expression (per unit lipid vs per 1000 adipocytes), there were modest changes in acyl CoA synthetase, diacylglycerol acyltransferase, and CD36 in response to acute sex hormone suppression.

Conclusions: Our results suggest estrogen and progesterone may have different effects on the regulation of FA metabolism and that acute sex steroid deficiency in women does not alter fat storage and oxidation.
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http://dx.doi.org/10.1210/jc.2015-4065DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4870847PMC
May 2016

The Sexual Dimorphism of Lipid Kinetics in Humans.

Front Endocrinol (Lausanne) 2015 2;6:103. Epub 2015 Jul 2.

Endocrine Research Unit, Mayo Clinic , Rochester, MN , USA.

In addition to the obvious differences in body shape, there are substantial differences in lipid metabolism between men and women. These differences include how dietary fatty acids are handled, the secretion and clearance of very low-density lipoprotein-triglycerides, the release rates of free fatty acids (FFA) from adipose tissue relative to energy needs, and the removal of FFA from the circulation, including the storage of FFA into adipose tissue via the direct uptake process. We will review what is known about these processes and how they may contribute to the sexual dimorphism of body fat distribution.
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http://dx.doi.org/10.3389/fendo.2015.00103DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4489151PMC
July 2015

Effects of weight loss via high fat vs. low fat alternate day fasting diets on free fatty acid profiles.

Sci Rep 2015 Jan 5;5:7561. Epub 2015 Jan 5.

1] Department of Exercise Science, Concordia University, Montreal, QC, Canada [2] Nutrition, Obesity, and Metabolism Lab, PERFORM Centre, Concordia University, Montreal, QC, Canada.

Cardiovascular disease risk is associated with excess body weight and elevated plasma free fatty acid (FFA) concentrations. This study examines how an alternate-day fasting (ADF) diet high (HF) or low (LF) in fat affects plasma FFA profiles in the context of weight loss, and changes in body composition and lipid profiles. After a 2-week weight maintenance period, 29 women (BMI 30-39.9 kg/m(2)) 25-65 years old were randomized to an 8-week ADF-HF (45% fat) diet or an ADF-LF (25% fat) diet with 25% energy intake on fast days and ad libitum intake on feed days. Body weight, BMI and waist circumference were assessed weekly and body composition was measured using dual x-ray absorptiometry (DXA). Total and individual FFA and plasma lipid concentrations were measured before and after weight loss. Body weight, BMI, fat mass, total cholesterol, LDL-C and triglyceride concentrations decreased (P < 0.05) in both groups. Total FFA concentrations also decreased (P < 0.001). In the ADF-LF group, decreases were found in several more FFAs than in the ADF-HF group. In the ADF-HF group, FFA concentrations were positively correlated with waist circumference. Depending on the macronutrient composition of a diet, weight loss with an ADF diet decreases FFA concentrations through potentially different mechanisms.
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http://dx.doi.org/10.1038/srep07561DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5378987PMC
January 2015

Sex and sex steroids: impact on the kinetics of fatty acids underlying body shape.

Horm Mol Biol Clin Investig 2014 Oct;20(1):15-23

Adult humans have a remarkable sexual dimorphism in body shape. Men tend to store relatively more fat in the upper body whereas women store more fat in the lower body. We do not have a complete understanding of the mechanisms underlying these differences, but we know that people who preferentially store abdominal fat are at greater risk of metabolic disease. It is also known that the changes in sex steroid concentrations during puberty and again with advancing age are accompanied by changes in body fat distribution. The objective of this review is to describe what has been learned regarding the mechanisms underlying changes in regional body fat distribution that occur as a result of changes in sex hormones and to delineate effects of sex steroids in modulating body composition.
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http://dx.doi.org/10.1515/hmbci-2014-0029DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4348027PMC
October 2014

Adipocyte fatty acid storage factors enhance subcutaneous fat storage in postmenopausal women.

Diabetes 2013 Mar 3;62(3):775-82. Epub 2012 Dec 3.

Endocrine Research Unit, Mayo Clinic, Rochester, Minnesota, USA.

Increases in weight have been associated with corresponding increases in insulin resistance in postmenopausal women. Although estrogen has significant impact on body fat and body fat distribution, the cellular mechanisms that influence this process are not yet known. We measured adipose tissue fatty acid (FA) storage and FA storage factors in 12 premenopausal and 11 postmenopausal women matched for age and body composition. Postmenopausal women had lower postprandial FA oxidation (indirect calorimetry), greater meal FA, and direct free FA (FFA) storage than premenopausal women, including two-fold greater meal FA storage in the femoral depot. The fed/fasted activities of adipose tissue lipoprotein lipase were not significantly different between premenopausal and postmenopausal women. In contrast, adipocyte acyl-CoA synthetase and diacylglycerol acyltransferase activities in postmenopausal women were significantly upregulated and were positively correlated with direct FFA storage rates. These findings suggest that the propensity for subcutaneous adipose tissue FA storage is increased in postmenopausal women, more so from changes in adipocyte FA storage factors than from adipose tissue lipoprotein lipase activity. Our results suggest that female sex steroids, most likely estrogen, have important effects on adipose tissue FA storage and FA oxidation that could promote fat gain in postmenopausal women.
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http://dx.doi.org/10.2337/db12-0912DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3581212PMC
March 2013

Effects of male hypogonadism on regional adipose tissue fatty acid storage and lipogenic proteins.

PLoS One 2012 20;7(2):e31473. Epub 2012 Feb 20.

Endocrine Research Unit, Mayo Clinic, Rochester, Minnesota, United States of America.

Testosterone has long been known to affect body fat distribution, although the underlying mechanisms remain elusive. We investigated the effects of chronic hypogonadism in men on adipose tissue fatty acid (FA) storage and FA storage factors. Twelve men with chronic hypogonadism and 13 control men matched for age and body composition: 1) underwent measures of body composition with dual energy x-ray absorptiometry and an abdominal CT scan; 2) consumed an experimental meal containing [(3)H]triolein to determine the fate of meal FA (biopsy-measured adipose storage vs. oxidation); 3) received infusions of [U-(13)C]palmitate and [1-(14)C]palmitate to measure rates of direct free (F)FA storage (adipose biopsies). Adipose tissue lipoprotein lipase, acyl-CoA synthetase (ACS), and diacylglycerol acetyl-transferase (DGAT) activities, as well as, CD36 content were measured to understand the mechanism by which alterations in fat storage occur in response to testosterone deficiency. Results of the study showed that hypogonadal men stored a greater proportion of both dietary FA and FFA in lower body subcutaneous fat than did eugonadal men (both p<0.05). Femoral adipose tissue ACS activity was significantly greater in hypogonadal than eugonadal men, whereas CD36 and DGAT were not different between the two groups. The relationships between these proteins and FA storage varied somewhat between the two groups. We conclude that chronic effects of testosterone deficiency has effects on leg adipose tissue ACS activity which may relate to greater lower body FA storage. These results provide further insight into the role of androgens in body fat distribution and adipose tissue metabolism in humans.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0031473PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3282778PMC
June 2012

Effects of estrogen and testosterone on resting energy expenditure in older men.

Obesity (Silver Spring) 2010 Dec 6;18(12):2392-4. Epub 2010 May 6.

Endocrine Research Unit, Mayo Clinic, Rochester, Minnesota, USA.

The mechanisms by which sex hormones cause changes in body composition are unclear. Sex steroid deficiency might directly reduce energy expenditure/fat oxidation and thereby predispose to increased body fat. Alternatively, sex steroid deficiency could result in lean tissue loss and thus reduced energy expenditure. Our objective was to examine the independent and combined effects of acute testosterone and estrogen withdrawal on respiratory exchange ratio (RER) and resting energy expenditure (REE) in men. The objective of the study was to examine the independent and combined effects of acute estrogen and testosterone withdrawal on RER and REE in men. A total of 54 men aged 50-80 years, BMI range of 17-35 kg/m(2) underwent a 3-week eugonadal run-in hormone-treatment period involving suppression of endogenous sex steroids using letrozole and leuprolide acetate (Lupron) while sex steroid concentrations were maintained with transdermal testosterone (T) and estradiol (E). A second Lupron injection was then given and participants were randomized to one of the following four 3-week treatment groups: group A (-T, -E), group B (-T, +E), group C (+T, -E), and group D (+T, +E). REE and RER were measured via indirect calorimetry before and after the 3-week treatment period. Three-week suppression and/or repletion of estrogen or testosterone did not produce changes in RER or REE within or between groups. We conclude that abrupt changes in sex steroids does not change resting substrate oxidation, indicating that changes that can be observed after more prolonged periods of deficiency are most likely due to direct effects of sex steroids on body composition.
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http://dx.doi.org/10.1038/oby.2010.98DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2919597PMC
December 2010

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

Am J Clin Nutr 2008 Oct;88(4):1134-41

Endocrine Research Unit, Mayo Clinic, Rochester, MN 55905, USA.

Background: Regional differences in meal fat storage may explain the preservation of fat accumulation in obese persons.

Objective: The objective was to determine whether meal fatty acid (FA) metabolism differs by sex and obesity phenotypes before and after weight loss.

Design: A [(3)H]triolein-containing meal was given to trace meal FA oxidation ((3)H(2)O generation) and adipose tissue uptake (abdominal subcutaneous and gluteal biopsy samples) in 13 upper-body obese (UOb) men, 9 UOb women, and 8 lower-body obese (LOb) women (study 1). Dual-energy X-ray absorptiometry and abdominal computed tomography were used to measure fat distribution. The subjects participated in a diet and exercise weight-loss program, after which 23 subjects returned for an identical study (study 2).

Results: In study 1, the storage of meal FA (mg meal fat/g adipose lipid) was greater in gluteal than in abdominal fat (P = 0.022) in LOb women, but not in UOb women or UOb men. UOb men stored a lesser percentage of meal FAs in both upper- and lower-body subcutaneous fat than did the LOb and UOb women (P = 0.001 and P = 0.044, respectively). The participants who returned for study 2 had lost 14.1 +/- 1.1 kg. Changes in the uptake of meal FAs followed a pattern indicative of obesity phenotype maintenance by group. The uptake of meal FAs increased in upper-body subcutaneous fat (P = 0.028) in weight-reduced UOb women and UOb men (P = 0.046) and decreased in lower-body fat (P = 0.025) in UOb men.

Conclusion: The differences in meal FA trafficking by obesity phenotype suggest that meal FA storage may play a role in regulating body fat distribution in obese persons.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2599905PMC
http://dx.doi.org/10.1093/ajcn/88.4.1134DOI Listing
October 2008

Why are we shaped differently, and why does it matter?

Am J Physiol Endocrinol Metab 2008 Sep 20;295(3):E531-5. Epub 2008 May 20.

Mayo Clinic, Rochester, MN 55905, USA.

Body fat distribution is an important predictor of metabolic abnormalities in obese humans. Dysregulation of free fatty acid (FFA) release, especially from upper body subcutaneous adipose tissue, appears to contribute substantially to these metabolic disturbances. Why different individuals preferentially store fat in upper vs. lower body subcutaneous fat or subcutaneous vs. visceral fat is not completely understood. Current evidence suggests that defects in regional lipolysis are not the cause of net fat retention in larger fat depots. Regional variations in the storage of fatty acids, both meal derived and direct reuptake, and storage of circulating FFAs that may help to explain why some depots expand at the expense of others have been reported. We review the quantitative data on regional lipolysis, meal, and FFA storage in adults to provide an overview of fat balance differences in adults with different fat distribution patterns.
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http://dx.doi.org/10.1152/ajpendo.90357.2008DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2536731PMC
September 2008

Moderate weight loss: a self-directed protocol for women.

Can J Diet Pract Res 2008 ;69(1):23-7

School of Dietetics and Human Nutrition, McGill University, Ste-Anne-de-Bellevue, QC.

This innovative, self-directed diet and physical activity program was designed to achieve moderate weight loss in women. Thirty-five overweight or obese hyperlipidemic women completed a 20-week weight loss study. The weight loss intervention consisted of a 20% decrease in energy intake through diet and a 10% increase in energy expenditure through physical activity. The diet consisted of 50-60% carbohydrates, 20% protein, and 20-30% fat. A personal trainer prescribed physical activity regimens. A progress-tracking system and monthly group sessions were used to maintain participant motivation throughout the weight loss period. Participants lost an average of 11.7 +/- 2.5 kg (p<0.001). The pattern of weight loss was linear (p<0.001) throughout the study period. Average weight loss per week was 0.59 +/- 0.55 kg. This 20-week program, combining a structured self-selected diet and independent preplanned physical activity with motivational strategies, resulted in weight loss comparable to that observed in more controlled interventions. The lower cost, ease of use, and outcome success make this approach potentially useful in a clinical setting.
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http://dx.doi.org/10.3148/69.1.2008.23DOI Listing
May 2008

Single nucleotide polymorphisms in ABCG5 and ABCG8 are associated with changes in cholesterol metabolism during weight loss.

J Lipid Res 2007 Dec 7;48(12):2607-13. Epub 2007 Sep 7.

School of Dietetics and Human Nutrition, McGill University, Ste-Anne-de-Bellevue, Québec, Canada.

The purpose of this study was to examine whether changes in cholesterol metabolism after weight loss were affected by single nucleotide polymorphisms (SNPs) in ABCG5 and ABCG8 genes. Thirty-five hypercholesterolemic women lost 11.7 +/- 2.5 kg (P < 0.001). Cholesterol kinetics were assessed using stable isotope techniques. TaqMan PCR was used to detect SNPs in ABCG5/G8. Homozygous Q604E variants in ABCG5 had larger (P < 0.05) reductions in cholesterol absorption and greater increases (P < 0.05) in synthesis in contrast to heterozygous and homozygous wild-type carriers. Heterozygous C54Y carriers had smaller declines (P = 0.047) in synthesis compared with homozygous variant individuals. The presence of at least one Y54 variant was associated with higher (P = 0.042) post-weight-loss synthesis compared with carriers of the C54 genotype. The direction of the results is consistent with cross-sectional studies on the effects of Q604E and C54Y polymorphisms on plasma cholesterol. SNPs in ABCG5/G8 were found to be associated with the response of cholesterol metabolism to weight loss. The evidence for associations between SNPs in ABCG5/G8 and various parameters of cholesterol metabolism indicates the potential effectiveness of establishing genetic screening tools to determine optimal lipid-lowering treatment routes for individuals during weight reduction.
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http://dx.doi.org/10.1194/jlr.M600452-JLR200DOI Listing
December 2007

An investigation of hormone and lipid associations after weight loss in women.

J Am Coll Nutr 2007 Jun;26(3):250-8

School of Dietetics and Human Nutrition, McGill University, Montreal, Canada.

Objective: The objectives of this study were to determine 1) whether the extent of weight loss is predictive of the degree of changes in hormone and lipid levels; 2) the interactions between energy regulating hormones after weight loss through an energy deficit/exercise protocol diet and exercise; 3) whether initial metabolic parameters are indicative of the extent of weight loss.

Methods: Thirty-five hyperlipidemic females (BMI 28-39 kg/m2) 35-60 years old participated in a six month weight loss trial. Weight loss resulted from a diet and exercise program that when combined produced a 30% energy deficit. Fasting plasma taken during 2 wk stabilization periods at the beginning and end of the study was analysed for lipids, hormone and glucose levels.

Results: Average weight loss was 11.7 +/- 2.5 kg (p < 0.0001). TC, LDL-C, and triacylglycerols decreased 9.3 +/- 9.5% (p < 0.0001), 7.4 +/- 12.2% (p < 0.001), and 26.8 +/- 19.6% (p < 0.05), respectively, while HDL-C increased (p < 0.05) by 8.2 +/- 16.3%. Leptin levels declined (p < 0.001) 48.9 +/- 16.0% and ghrelin levels rose (p < 0.001) 21.2 +/- 26.7%. While overall levels of adiponectin did not differ, individual values changed such that weight loss predicted increases in adiponectin levels. Though initial weight did not predict weight loss, baseline lipid and insulin levels positively predicted weight loss.

Conclusion: Initial metabolic parameters may be predictors of weight loss. Beneficial effects of weight loss as achieved through diet and exercise on measured parameters indicate moderate weight loss reduces key risk factors of cardiovascular disease in overweight individuals.
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http://dx.doi.org/10.1080/07315724.2007.10719608DOI Listing
June 2007

Validation of hand-held bioelectrical impedance analysis with magnetic resonance imaging for the assessment of body composition in overweight women.

Am J Hum Biol 2007 May-Jun;19(3):429-33

School of Dietetics and Human Nutrition, McGill University, Québec, Canada.

Methods of assessing body composition suitable for use in clinical trials should be accurate, reliable, and easy to perform. One such technique routinely implemented is hand-held bioelectrical impedance analysis (BIA). The validity of this method, however, in body composition assessment of overweight women is not known. The aim of this study was to validate the hand-held BIA technique with magnetic resonance imaging (MRI) for the assessment of body composition in overweight women. Fat mass, percent fat mass, fat-free mass, and percent fat-free mass values estimated by hand-held BIA were compared to those measured by MRI. Thirty-one Caucasian women (50.1 +/- 8.2 years, body mass index of 26.9 +/- 3.1 kg/m(2)) participated in the study. BIA measurements were highly reproducible (technical error (TE) was 0.06 +/- 0.07 kg for fat mass and 0.08 +/- 0.11% for percent fat mass), but were significantly different (P < 0.0001) for each body composition parameter when compared to MRI. BIA underestimated fat mass by 2.3 +/- 3.3 kg and percent fat mass by 5.6 +/- 3.9%. Likewise, BIA overestimated fat free mass by 7.4 +/- 2.7 kg and percent fat free mass by 5.6 +/- 3.2%. No relationship between the bias and the mean of the two measurements was noted suggesting that bias is not related to measurement size. Although hand-held BIA gives reproducible findings, the bias noted for all body composition parameters puts into question the validity of this regional impedance device for use in clinical trials in overweight women.
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http://dx.doi.org/10.1002/ajhb.20609DOI Listing
June 2007

Physiological and therapeutic factors affecting cholesterol metabolism: does a reciprocal relationship between cholesterol absorption and synthesis really exist?

Life Sci 2007 Jan 17;80(6):505-14. Epub 2006 Oct 17.

School of Dietetics and Human Nutrition, McGill University, Montreal, Quebec, Canada.

Cholesterol absorption and synthesis contribute to maintaining cholesterol homeostasis. Several physiological and therapeutic factors affect cholesterol homeostasis, including: genetics, circadian rhythm, body weight, plant sterols, ezetimibe, and statin therapy. The present objective is to determine the main vector, i.e. cholesterol absorption or synthesis, affected by each of these factors, and to examine whether an alteration in one vector is linked to a reciprocal change in the other. Current techniques used to assess cholesterol absorption and synthesis are also reviewed. Review of physiological factors affecting cholesterol metabolism suggest a reciprocal relationship between these two vectors. Carriers of the E2 isoform of apolipoprotein E and ATP binding cassette (ABC) G8 19H (exon 1 mutation) show a decrease in cholesterol absorption accompanied by a corresponding increase in synthesis. Circadian rhythm affects cholesterol synthesis, however, its effect on absorption has yet to be established. Obese subjects show an increase in cholesterol synthesis with a subsequent decrease in cholesterol absorption. Weight loss down regulates cholesterol synthesis, but has little or no effect on absorption. In the case of therapeutic factors, plant sterols and stanols inhibit cholesterol absorption, which results in a compensatory increase in synthesis. Ezetimibe also decreases intestinal absorption, while reciprocally increasing synthesis. Statin therapy down regulates synthesis, which is accompanied by a rise in absorption. These findings suggest that a change in one vector, fairly consistently, results in a compensatory and opposing change in the other. An understanding of this reciprocal relationship between cholesterol absorption and synthesis may allow for the development of more effective interventions for dyslipidemic disorders.
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http://dx.doi.org/10.1016/j.lfs.2006.10.006DOI Listing
January 2007

Effect of weight loss resulting from a combined low-fat diet/exercise regimen on low-density lipoprotein particle size and distribution in obese women.

Metabolism 2006 Oct;55(10):1302-7

School of Dietetics and Human Nutrition, McGill University, Montreal, Quebec, Canada, H9X 3V9.

Weight loss resulting from diet interventions has been shown to favorably affect low-density lipoprotein (LDL) particle size and distribution, and, hence, decrease cardiovascular disease risk. However, the effect of a dietary weight loss strategy when combined with exercise, on LDL electrophoretic characteristics, has yet to be tested. This study examined the effect of a weight loss intervention that combined a low-fat diet with moderate endurance training, on LDL particle size and distribution in obese women. Thirty obese, hypercholesterolemic women participated in a controlled longitudinal weight loss trial, which consisted of (1) a 2-week pre-stabilization phase, (2) a 20-week weight loss phase, and (3) a 2-week post-stabilization phase. Weight reduction resulted from a low-fat diet (<30% fat, 50%-60% carbohydrate, 20% protein) combined with an endurance training program (>40 minutes moderate training, 3 times per week). Mean weight loss was 14.8% (P < .01) of initial body weight. Total, LDL cholesterol, and triacylglycerol concentrations decreased (P < .01) by 8.9%, 7.5%, and 27.1%, respectively, whereas high-density lipoprotein cholesterol concentrations increased (P < .01) by 9.9%. No significant differences were noted for LDL peak or integrated particle size. The relative proportion of small, medium, and large particles was not significantly different posttreatment. Estimated cholesterol concentrations in large- and medium-sized LDL particles decreased (P < .05) by 15.3% and 5.9%, respectively, as a result of weight loss. No effect was noted for estimated cholesterol concentrations in small size LDL particles. In conclusion, these findings suggest that weight loss, resulting from a low-fat diet/exercise program, has only a minimal effect on LDL particle size and distribution.
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http://dx.doi.org/10.1016/j.metabol.2006.05.014DOI Listing
October 2006