Although differences in body composition parameters among African American (AA), Hispanic American (HA) and European American (EA) children are well documented, the factors underlying these differences are not completely understood. Environmental and genetic contributors have been evaluated as contributors to observed differences. This study evaluated the extent to which African or European ancestral genetic background influenced body composition and fat distribution in 301 peripubertal AA (n=107), HA (n=79) and EA (n=115) children aged 7–12.
Estimates of African admixture (AFADM) and European admixture (EUADM) were obtained for every subject using 142 ancestry informative DNA markers. Dual energy X-ray absorptiometry and computed tomography scanning were used to determine body composition and abdominal fat distribution, respectively. Multiple regression models were conducted to evaluate the contribution of admixture estimates to body composition and fat distribution.
Greater AFADM was associated with lower fat mass (P=0.0163), lower total abdominal adipose tissue (P=0.0006), lower intra-abdominal adipose tissue (P=0.0035), lower subcutaneous abdominal adipose tissue (P=0.0115) and higher bone mineral content (BMC) (P=0.0253), after adjusting for socio-economic status, sex, age, height, race/ethnicity and pubertal status. Greater EUADM was associated with lower lean mass (LM) (P=0.0056).
These results demonstrate that ancestral genetic background contributes to racial/ethnic differences in body composition above and beyond the effects of racial/ethnic classification and suggest a genetic contribution to total body fat accumulation, abdominal adiposity, LM and BMC.
European genetic admixture; race/ethnicity; abdominal adiposity; bone mineral content; lean mass
To examine the associations of antibiotic exposures during the first 2 years of life and the development of body mass over the first 7 years of life.
Longitudinal birth cohort study.
A total of 11532 children born at ≥2500 g in the Avon Longitudinal Study of Parents and Children (ALSPAC), a population-based study of children born in Avon, UK in 1991–1992.
Exposures to antibiotics during three different early-life time windows (<6 months, 6–14 months, 15–23 months), and indices of body mass at five time points (6 weeks, 10 months, 20 months, 38 months and 7 years).
Antibiotic exposure during the earliest time window (<6 months) was consistently associated with increased body mass (+0.105 and +0.083 s.d. unit, increase in weight-for-length Z-scores at 10 and 20 months, P<0.001 and P=0.001, respectively; body mass index (BMI) Z-score at 38 months +0.067 s.d. units, P=0.009; overweight OR 1.22 at 38 months, P=0.029) in multivariable, mixed-effect models controlling for known social and behavioral obesity risk factors. Exposure from 6 to 14 months showed no association with body mass, while exposure from 15 to 23 months was significantly associated with increased BMI Z-score at 7 years (+0.049 s.d. units, P=0.050). Exposures to non-antibiotic medications were not associated with body mass.
Exposure to antibiotics during the first 6 months of life is associated with consistent increases in body mass from 10 to 38 months. Exposures later in infancy (6–14 months, 15–23 months) are not consistently associated with increased body mass. Although effects of early exposures are modest at the individual level, they could have substantial consequences for population health. Given the prevalence of antibiotic exposures in infants, and in light of the growing concerns about childhood obesity, further studies are needed to isolate effects and define life-course implications for body mass and cardiovascular risks.
antibiotics; human microbiome; body mass; ALSPAC
There is emerging literature demonstrating a relationship between the timing of feeding and weight regulation in animals. However, whether the timing of food intake influences the success of a weight-loss diet in humans is unknown.
To evaluate the role of food-timing in weight-loss effectiveness in a sample of 420 individuals who followed a 20-week weight-loss treatment.
Participants (49.5% females; age [mean+/−SD]: 42±11 years; BMI: 31.4±5.4 kg/m2) were grouped in early-eaters and late-eaters, according to the timing of the main meal (lunch in this Mediterranean population). 51% of the subjects were early-eaters and 49% were late-eaters (lunch time before and after 3:00 PM, respectively), energy intake and expenditure, appetite hormones, CLOCK genotype, sleep duration and chronotype were studied.
Late lunch eaters lost less weight and displayed a slower weight-loss rate during the 20 weeks of treatment than early-eaters (P=0.002). Surprisingly, energy intake, dietary composition, estimated energy expenditure, appetite hormones and sleep duration was similar between both groups. Nevertheless, late-eaters were more evening-types, had less energetic breakfasts, and skipped breakfast more frequently that early-eaters (P<0.05). CLOCK rs4580704 SNP associated with the timing of the main meal (P=0.015) with a higher frequency of minor allele (C) carriers among the late-eaters (P=0.041). Neither sleep duration, nor CLOCK SNPs or Morning/Evening chronotype was independently associated with weight-loss (P>0.05).
Eating late may influence the success of weight-loss therapy. Novel therapeutic strategies should incorporate not only the caloric intake and macronutrient distribution—as is classically done—but also the timing of food.
Timing of food intake; obesity; weight loss; dietary treatment; circadian
Primary care practitioners (PCPs) have been encouraged to screen all adults for obesity and to offer behavioral weight loss counseling to affected individuals. However, there is limited research and guidance on how to provide such intervention in primary care settings. This led the National Heart, Lung, and Blood Institute (NHLBI) in 2005 to issue a request for applications to investigate the management of obesity in routine clinical care. Three institutions were funded under a cooperative agreement to undertake the Practice-based Opportunities for Weight Reduction (POWER) trials. The present article reviews selected randomized controlled trials, published prior to the initiation of POWER, and then provides a detailed overview of the rationale, methods, and results of the POWER trial conducted at the University of Pennsylvania (POWER-UP). POWER-UP’s findings are briefly compared with those from the two other POWER Trials, conducted at Johns Hopkins University and Harvard University/Washington University. The methods of delivering behavioral weight loss counseling differed markedly across the three trials, as captured by an algorithm presented in the article. Delivery methods ranged from having medical assistants and PCPs from the practices provide counseling to using a commercially-available call center, coordinated with an interactive web-site. Evaluation of the efficacy of primary care-based weight loss interventions must be considered in light of costs, as discussed in relation to the recent treatment model proposed by the Centers for Medicare and Medicaid Services.
weight loss; behavioral weight loss counseling; lifestyle modification; primary care practice; cost-effectiveness
Data on the cost-effectiveness of the behavioral treatment of obesity are not conclusive. The cost-effectiveness of treatment in primary care settings is particularly relevant.
We conducted a within-trial cost-effectiveness analysis of a primary care-based obesity intervention. Study participants were randomized to: Usual Care (quarterly visits with their primary care provider); Brief Lifestyle Counseling (Brief LC; quarterly provider visits plus monthly weight loss counseling visits; or Enhanced Brief Lifestyle Counseling (Enhanced Brief LC; all above interventions, plus choice of meal replacements or weight loss medication). A health care payer perspective was used. Intervention costs were estimated from tracking data obtained prospectively. Quality adjusted life years (QALYs) were estimated with the EuroQol-5D. We estimated cost per kilogram-year of weight loss and cost per QALY.
Weight losses after 2 years were 1.7, 2.9, and 4.6 kg for Usual Care, Brief LC, and Enhanced Brief LC, respectively (p = 0.003 for comparison of Enhanced Brief LC vs. Usual Care). The incremental cost per kilogram-year lost was $292 for Enhanced Brief LC compared to Usual Care (95% CI $38 to $394). The incremental cost per QALY was $115,397, but the 95% CI were undefined. Comparison of short term cost per kg with published estimates of longer term cost per QALYs suggested that the intervention could be cost-effective over the long term (≥ 10 years).
A primary care intervention that included monthly counseling visits and a choice of meal replacements or weight loss medication could be a cost-effective treatment for obesity over the long term. However, additional studies are needed on the cost-effectiveness of behavioral treatment of obesity.
Obesity; Reducing Diet; Primary Care; Costs; Cost-Effectiveness
Depression has been associated with increased risk of cardiovascular disease (CVD). The inflammatory marker C-reactive protein (CRP) has also been identified as an independent predictor of short- and long-term CVD events. Inflammation may influence the relationship between depression and CVD.
The objective of this study was to investigate the association between symptoms of depression and high-sensitivity CRP (hs-CRP) in an obese clinical population. We also sought to determine whether this relationship was different in men and women, given prior reports of a gender effect.
Symptoms of depression and hs-CRP were measured in 390 participants enrolled in a weight loss intervention trial that was delivered in a primary care setting. Symptoms of depression were evaluated with the Patient Health Questionnaire-8 (PHQ-8), in which a score > 10 is consistent with major depression.
A total of 58 (15.2%) participants reported a PHQ-8 score ≥ 10. The median (interquartile range) hs-CRP concentration was significantly higher in participants with symptoms consistent with major depression [7.7 (4.2–13) mg/L] compared to those without depression [5.1 (3–9.7) mg/L; p<0.01]. Symptoms consistent with major depression were significantly associated with log-transformed hs-CRP concentrations in an analysis adjusted for age, gender, obesity class, and other metabolic variables (p=0.04). When interaction by gender was examined, this relationship remained significant in men (p<0.01) but not in women (p=0.32).
Symptoms consistent with major depression were significantly associated with hs-CRP in men only, even after adjusting for age, obesity class, metabolic variables, and medications known to affect inflammation. This finding suggests that there are biologic differences between men and women that may modify the relationship between hs-CRP and depression. Further studies are needed to elucidate the biologic basis for these findings.
high-sensitivity C-reactive protein; depression; obesity; gender
To investigate the effects of three weight loss interventions on cardiometabolic risk factors including blood pressure, lipids, glucose, and markers of insulin resistance and inflammation. We also examined whether categories of incremental weight change conferred greater improvements on these parameters.
This 2-year trial was conducted in a primary care setting and included 390 obese participants who were randomly assigned to one of three interventions: 1) Usual Care [quarterly primary care provider (PCP) visits that included education about weight management]; 2) Brief Lifestyle Counseling (quarterly PCP visits plus monthly behavioral counseling provided by a trained auxiliary healthcare provider); or 3) Enhanced Brief Lifestyle Counseling (the same care as described for the previous intervention, plus weight loss medications or meal replacements). The primary outcome was change in cardiometabolic risk factors among groups.
At month 24, participants in Enhanced Brief Lifestyle Counseling lost significantly more weight than those in Usual Care (4.6 vs. 1.7 kg), with no other significant differences between groups. Enhanced Brief Lifestyle Counseling produced significantly greater improvements in HDL cholesterol and triglyceride levels at one or more assessments, compared with the other two interventions. Markers of insulin resistance also improved significantly more in this group throughout the 2 years. Collapsing across the three groups, greater weight loss was associated with greater improvements in triglycerides, HDL cholesterol, and markers of insulin resistance and inflammation at month 24, but was not significantly associated with reductions in blood pressure, total cholesterol, and LDL cholesterol at any time.
Enhanced Brief Lifestyle Counseling, which produced the largest weight loss, was generally associated with the greatest improvements in cardiovascular risk factors. These findings suggest that an intensive weight loss intervention, delivered in a primary care setting, can help obese individuals improve some cardiometabolic risk factors.
lifestyle intervention; weight loss; cardiometabolic risk factors; lipids; insulin resistance
This study investigated changes in quality of life in men and women who participated in a primary care-based weight loss intervention.
Participants were enrolled in a two-year randomized clinical trial (POWER-UP) conducted at the University of Pennsylvania and six affiliated primary care practices. Inclusion criteria included the presence of obesity (body mass index of 30–50 kg/m2) and at least two components of the metabolic syndrome.
Main Outcome Measures
Quality of life was assessed by three measures: Short Form (12) Health Survey (SF-12); Impact of Weight on Quality of Life-Lite (IWQOL-Lite); and the EuroQol-5D.
Six months after the onset of treatment, and with a mean weight loss of 3.9 ± .30 kg, participants reported significant improvements on all of the measures of interest with the exception of the Mental Component Score of the SF-12. These changes remained significantly improved from baseline at month 24, with the exception of the EuroQol-5D. Many of these improvements were correlated with the magnitude of weight loss and, for the most part, were consistent across gender and race.
Individuals with obesity and components of the metabolic syndrome reported significant improvements in most domains of quality of life with a modest weight loss of 3.7% of initial weight, achieved within the first 6 months of treatment. The majority of these improvements were maintained at month 24, when participants had lost 3.0% of their weight.
quality of life; obesity; lifestyle modification; weight loss
To examine changes in eating behaviors and physical activity, as well as predictors of weight loss success, in obese adults who participated in a 2-year behavioral weight loss intervention conducted in a primary care setting.
A longitudinal, randomized-controlled, multi-site trial.
390 obese (body mass index, 30 to 50 kg/m2) adults, ≥21 yr, in the Philadelphia region.
Participants were assigned to one of three interventions 1) Usual Care [Quarterly primary care provider (PCP) visits that included education on diet and exercise]; 2) Brief Lifestyle Counseling [quarterly PCP visits plus monthly Lifestyle Counseling (LC) sessions about behavioral weight control]; or 3) Enhanced Brief LC (the previous intervention with a choice of meal replacements or weight loss medication).
At month 24, participants in both Brief LC and Enhanced Brief LC reported significantly greater improvements in mean (±SE) dietary restraint than those in Usual Care (4.4±0.5, 4.8±0.5, and 2.8±0.5, respectively; both ps≤0.016). The percentage of calories from fat, along with fruit and vegetable consumption, did not differ significantly among the three groups. The Brief LC and Enhanced Brief LC groups both reported significantly greater energy expenditure (kcal/week) at month 24 than Usual Care (+593.4±175.9, +415.4±179.6, and −70.4±185.5, respectively; both ps≤0.037). The strongest predictor of weight loss at month 6 (partial R2=33.4%, p<0.0001) and at month 24 (partial R2=19.3%, p<0.001) was food records completed during the first 6 months. Participants who achieved a 5% weight loss at month 6 had 4.7 times greater odds of maintaining a 5% weight loss at month 24.
A behavioral weight loss intervention delivered in a primary care setting can result in significant weight loss, with corresponding improvements in eating restraint and energy expenditure. Moreover, completion of food records, along with weight loss at month 6, is a strong predictor of long-term weight loss.
lifestyle intervention; weight loss; Eating Inventory; food intake; physical activity
Perivascular adipose tissue may be associated with the amount of local atherosclerosis. We developed a novel and reproducible method to standardize volumetric quantification of periaortic adipose tissue by computed tomography (CT) and determined the association with anthropometric measures of obesity, and abdominal adipose tissue.
Measurements of adipose tissue were performed in a random subset of participants from the Framingham Heart Study (n=100) who underwent multidetector CT of the thorax (ECG triggering, 2.5 mm slice thickness) and the abdomen (helical CT acquisition, 2.5 mm slice thickness). Abdominal periaortic adipose tissue (AAT) was defined by a 5 mm cylindrical region of interest around the aortic wall; thoracic periaortic adipose tissue (TAT) was defined by anatomic landmarks. TAT and AAT were defined as any voxel between −195 HU to −45HU and volumes were measured using dedicated semiautomatic software. Measurement reproducibility and association with anthropometric measures of obesity, and abdominal adipose tissue were determined.
The intra- and inter-observer reproducibility for both AAT and TAT was excellent (ICC: 0.97, 0.97; 0.99, and 0.98, respectively). Similarly, the relative intra-and inter-observer difference was small for both AAT (−1.85±1.28% and 7.85±6.08%; respectively) and TAT (3.56±0.83% and −4.56±0.85%, respectively). Both AAT and TAT were highly correlated with visceral abdominal fat (r=0.65 and 0.77, p<0.0001 for both) and moderately correlated with subcutaneous abdominal fat (r=0.39 and 0.42, p<0.0001 and p=0.009), waist circumference (r=0.49 and 0.57, p<0.0001 for both), and body mass index (r=0.47 and 0.58, p<0.0001 for both).
Standardized semiautomatic CT-based volumetric quantification of periaortic adipose tissue is feasible and highly reproducible. Further investigation is warranted regarding associations of periaortic adipose tissue with other body fat deposits, cardiovascular risk factors, and clinical outcomes.
Adipose Tissue; Intra-Abdominal Fat; Tomography; Spiral Computed; Framingham Heart Study; Metabolic Risk Factors
Vitamin D deficiency has been consistently associated with obesity. However, it is unclear whether vitamin D deficiency is the cause or consequence of obesity. We investigated this question by evaluating the association between genetic variants in vitamin D metabolism pathway genes and obesity-related traits. Using directly genotyped and imputed data from a genome-wide association (GWA) study of 6,922 women aged 25–70 years, we examined the association of 198 SNPs in vitamin D pathway genes (CYP27A1, CYP27B1, CYP24A1, CYP2R1, GC, and VDR) with body mass index (BMI) and body weight. Per allele beta (β) estimates were calculated for this association using linear regression models, controlling for age, square of age, menopausal status, and sample sets. Overall, only two SNPs (rs2248359 in CYP24A1 and rs10832313 in CYP2R1) had a nominally significant association with BMI and weight (P=0.02 for both) with no variation observed by menopausal status, physical activity, or dietary energy intake. None of the SNPs examined in the VDR gene were associated with BMI or weight. Our findings suggest that common genetic variations in vitamin D pathway genes do not play a major role in obesity among Chinese women.
genetic variants; body mass index; body weight; obesity; vitamin D pathway; genome-wide association study; women; China
Although it is known that obesity increases the risk of endometrial cancer and is linked to higher mortality rates in the general population, the association between obesity and mortality among endometrial cancer survivors is unclear. We performed a medline search using exploded Mesh keywords ‘endometrial neoplasms/’ and (‘body mass index/’ or ‘obesity/’) and (‘survival analysis/’ or ‘mortality/’ or (survivor* or survival*).mp.). We also inspected bibliographies of relevant papers to identify related publications. Our search criteria yielded 74 studies, 12 of which met inclusion criteria. Four of the included studies reported a statistically or marginally significant association between obesity and higher all cause mortality among endometrial cancer survivors after multivariate adjustment. The suggestive association between body mass index and higher all cause mortality among women with endometrial cancer was comparable to the magnitude of association reported in prospective studies of healthy women. Of the five studies that examined progression-free survival and the two studies reporting on disease-specific mortality, none reported an association with obesity. Future studies are needed to understand disease-specific mortality, the importance of obesity-onset timing and whether mechanisms of obesity-related mortality in this population of women differ from those of the general population.
endometrial neoplasms; survivorship; mortality; body mass index
Low-density lipoprotein-related receptor protein 1 (LRP1) is a multi-functional endocytic receptor and signaling molecule that is expressed in adipose and the hypothalamus. Evidence for a role of LRP1 in adiposity is accumulating from animal and in vitro models, but data from human studies are limited. The study objectives were to evaluate (i) relationships between LRP1 genotype and anthropometric traits, and (ii) whether these relationships were modified by dietary fatty acids.
DESIGN AND METHODS
We conducted race/ethnic-specific meta-analyses using data from 14 studies of US and European whites and 4 of African Americans to evaluate associations of dietary fatty acids and LRP1 genotypes with body mass index (BMI), waist circumference and hip circumference, as well as interactions between dietary fatty acids and LRP1 genotypes. Seven single-nucleotide polymorphisms (SNPs) of LRP1 were evaluated in whites (N up to 42 000) and twelve SNPs in African Americans (N up to 5800).
After adjustment for age, sex and population substructure if relevant, for each one unit greater intake of percentage of energy from saturated fat (SFA), BMI was 0.104 kg m−2 greater, waist was 0.305 cm larger and hip was 0.168 cm larger (all P<0.0001). Other fatty acids were not associated with outcomes. The association of SFA with outcomes varied by genotype at rs2306692 (genotyped in four studies of whites), where the magnitude of the association of SFA intake with each outcome was greater per additional copy of the T allele: 0.107 kg m−2 greater for BMI (interaction P=0.0001), 0.267 cm for waist (interaction P=0.001) and 0.21 cm for hip (interaction P=0.001). No other significant interactions were observed.
Dietary SFA and LRP1 genotype may interactively influence anthropometric traits. Further exploration of this, and other diet x genotype interactions, may improve understanding of interindividual variability in the relationships of dietary factors with anthropometric traits.
low-density lipoprotein receptor-related protein 1; SNPs; saturated fatty acids; gene–diet interactions
The orexin peptides and their two receptors are involved in multiple physiological processes, including energy homeostasis, arousal, stress and reward. Higher signaling of the orexin peptides at the orexin receptors (OXR) protects against obesity, but it is less clear how their activation in different brain regions contributes to this behavioral output. This review summarizes the evidence available for a role of central OXR in energy homeostasis and their contribution to obesity. A detailed analysis of anatomical, cellular and behavioral evidence shows that modulation of energy homeostasis by the OXR is largely dependent upon anatomical and cellular context. It also shows that obesity resistance provided by activation of the OXR is distributed across multiple brain sites with site-specific actions. We suggest that understanding the role of the OXR in the development of obesity requires considering both specific mechanisms within brain regions and interactions of orexinergic input between multiple sites.
orexin; orexin receptors; hypothalamus; energy metabolism; diet-induced obesity; spontaneous physical activity
Obesity and shorter telomeres are commonly associated with elevated risk for age-related diseases and mortality. Whether telomere length (TL) may be associated with obesity or variations in adiposity is not well established. Therefore, we set out to test the hypothesis that TL may be a risk factor for increased adiposity using data from a large population-based cohort study.
Levels of adiposity were assessed in 6 ways (obesity status, body mass index or BMI, the percentage of body fat or % body fat, leptin, visceral and subcutaneous fat mass) in 2,721 elderly subjects (42% black and 58% white). Associations between TL measured in leukocytes at baseline and adiposity traits measured at baseline and 3 of these traits after 7 years of follow-up were tested using regression models adjusting for important covariates. Additionally, we look at weight changes and relative changes in BMI and % body fat between baseline and follow-up.
At baseline, TL was negatively associated with % body fat (β = −0.35 ± 0.09, p = 0.001) and subcutaneous fat (β = −2.66 ± 1.07, p = 0.01), and positively associated with leptin after adjusting for % body fat (β = 0.32 ± 0.14, p = 0.001), but not with obesity, BMI or visceral fat. Prospective analyses showed that longer TL was associated with positive percent change between baseline and 7-year follow-up for both BMI (β = 0.48 ± 0.20, p = 0.01) and % body fat (β = 0.42 ± 0.23, p = 0.05).
Our study suggests that shorter TL may be a risk factor for increased adiposity. Coupling with previous reports on their reversed roles, the relationship between adiposity and TL may be complicated and warrant more prospective studies.
Obesity; telomere length; adiposity; telomeres
Fatty liver disease (FLD) is characterized by increased intrahepatic triglyceride content with or without inflammation and is associated with obesity, and features of the metabolic syndrome. Several recent GWAS have reported an association between SNP rs738409 in the PNPLA3 gene and FLD. Liver attenuation (Hounsfield Units, HU) by computed tomography is a non-invasive measure of liver fat, with lower values of HU indicating higher liver fat content. Clinically, a liver attenuation (LA) value of ≤ 40 HU indicates moderate-to-severe hepatic steatosis.
We investigated whether missense rs738409 PNPLA3 interacted with abdominal visceral adipose tissue volume (cm3) to reduce liver attenuation (i.e. increased liver fat) in 1,019 European American men and 1,238 European American women from the Family Heart Study.
We used linear regression to test the additive effect of genotype, abdominal visceral adipose tissue (VAT), and their multiplicative interaction on LA adjusted for age, BMI, HDL-cholesterol, insulin resistance, serum triglycerides, abdominal subcutaneous adipose tissue, and alcohol intake.
In men and women combined, the interaction between each copy of the rs738409 variant allele (MAF 0.23) and 100cm3/150mm slice VAT decreased LA by 2.68±0.35 HU (p < 0.01). The interaction of 100cm3 VAT and the variant allele was associated with a greater decrease in LA in women than men (−4.8±0.6 and −2.2±0.5 HU, respectively).
The interaction between genotype and VAT volume suggest key differences in the role of PNPLA3 genotype in conjunction with abdominal VAT in liver fat accrual. The stronger association of the PNPLA3 genotype and liver fat in women suggests that women may be more sensitive to liver fat accumulation in the setting of increased visceral fat, compared to men. The presence of the PNPLA3 variant genotype, particularly in the context of high visceral adipose tissue content may play an important role in FLD.
Fatty liver disease; PNPLA3 locus; abdominal obesity; visceral obesity
Adipose tissue expansion during obesity is associated with a state of low-grade inflammation and an increase in macrophage infiltration, which predisposes to insulin resistance and vascular malfunction. Growing evidence suggests that vitamin D3 has immunoregulatory effects and adipose tissue could be a target for vitamin D3 action. Preadipocytes, one of the major cell types in adipose tissue, are actively involved in inflammatory processes.
This study investigated whether the active form of vitamin D3 (1,25(OH)2D3) affects the production of proinflammatory chemokines/cytokines and the monocyte recruitment by human preadipocytes.
Methods and Results
The secretion levels of MCP-1, IL-8 and IL-6 were significantly higher in preadipocytes than in differentiated adipocytes, suggesting that preadipocytes could be a major source of proinflammatory mediators. Cytokine profile analysis revealed that 1,25(OH)2D3 (10 nM) markedly reduced the release of MCP-1, IL-6 and IL-8 by preadipocytes. The involvement of NFκB signaling was shown by the upregulation of IκBα protein abundance by 1,25(OH)2D3 in preadipocytes. In addition, 1,25(OH)2D3 was able to decrease the migration of THP-1 monocytes. Treatment with proinflammatory stimuli, including macrophage conditioned (MC) medium, TNFα and IL-1β, led to a marked increase in protein release of MCP-1 and IL-6 by preadipocytes. Pretreatment with 1,25(OH)2D3 (10 nM and 100 nM) significantly decreased the stimulatory effects of MC medium, TNFα and IL-1β on MCP-1 expression and protein release, although the effect on stimulated release of IL-6 was less potent.
These results demonstrate that 1,25(OH)2D3 decreases the production of MCP-1 and other proinflammatory mediators by preadipocytes and reduces monocyte migration. Thus, vitamin D3 may protect against adipose tissue inflammation by disrupting the deleterious cycle of macrophage recruitment.
1,25-dihydroxyvitamin D3; preadipocytes; MCP-1; monocytes; inflammation; obesity
Obesity prevalence stabilized in the U.S. in the first decade of the 2000s. However, obesity prevalence may resume increasing if younger generations are more sensitive to the obesogenic environment than older generations.
We estimated cohort effects for obesity prevalence among young adults born in the 1980s. Using data collected from the National Health and Nutrition Examination Survey between 1971 and 2008, we calculated obesity for respondents aged between 2 and 74 years. We used the median polish approach to estimate smoothed age and period trends; residual non-linear deviations from age and period trends were regressed on cohort indicator variables to estimate birth cohort effects.
After taking into account age effects and ubiquitous secular changes, cohorts born in the 1980s had increased propensity to obesity versus those born in the late 1960s. The cohort effects were 1.18 [95% CI: 1.01, 1.07] and 1.21 [95% CI: 1.02, 1.09] for the 1979–1983 and 1984–1988 birth cohorts, respectively. The effects were especially pronounced in Black males and females but appeared absent in White males.
Our results indicate a generational divergence of obesity prevalence. Even if age-specific obesity prevalence stabilizes in those born before the 1980s, age-specific prevalence may continue to rise in the 1980s cohorts, culminating in record high obesity prevalence as this generation enters its ages of peak obesity prevalence.
Age factors; Obesity; Young adult; Developmental origins; Epidemiology; Models; statistical
The inverse relationship between adiposity and high-density lipoprotein (HDL) cholesterol is well established, however, we believe that its usual representation lacks an important dimension. The purpose of this study is to test whether the relationship depends upon past weight history in addition to current weight.
Physician-supplied medical data were compared to questionnaires from a national cross-sectional survey.
6847 men who ran between zero and 171 km per week.
Self-reported current weight, greatest lifetime weight and body circumferences were compared to physician-supplied data for plasma concentrations of HDL cholesterol, low-density lipoprotein (LDL) cholesterol, and triglycerides.
Current HDL-cholesterol levels were greatest in those runners with the greatest weight loss since their maximum lifetime weight and the greatest reductions in circumference of their waist, hip, and chest since their maximum weight. Plasma levels of triglycerides, LDL-cholesterol, and total cholesterol/HDL-cholesterol were also significantly lower for runners showing the greatest decreases in total and regional adiposity since their maximum weight. The results remained significant when adjusted for current body mass index and running mileage.
These results suggest that the lipoprotein concentrations of runners are in part dependent upon whether the current weight is relatively high or low within the historical range of weights experienced by the individual.
Exercise; running; physical activity; high-density lipoproteins; low-density lipoproteins; adiposity; weight set-point
Introduction and Objectives
The frequency of copper deficiency and clinical manifestations following roux-en-y gastric bypass (RYGB) surgery is not yet clear. Objectives were to determine the prevalence and incidence of copper deficiency in patients who have undergone RYGB.
Design and Methods
We sought to determine the number of RYGB patients undergoing medical and nutritional follow-up visits at the Emory Bariatric Center who experienced copper deficiency and associated hematological and neurological complaints (n = 136). Separately, in patients followed longitudinally before and during 6 and 24 months following RYGB surgery, we obtained measures of copper status (n = 16). Systemic blood cell counts and measures of copper, zinc and ceruloplasmin were determined using standardized assays in reference laboratories including atomic absorption spectrometry and immunoassays.
Thirteen patients were identified to have copper deficiency suggesting a prevalence of copper deficiency of 9.6%, and the majority of these had concomitant complications including anemia, leukopenia and various neuro-muscular abnormalities. In the longitudinal study, plasma copper concentrations and ceruloplasmin activity decreased over 6 and 24 months following surgery, respectively (P<0.05), but plasma zinc concentrations did not change. A simultaneous decrease in white blood cells was observed (P<0.05). The incidence of copper deficiency in these subjects was determined to be 18.8%.
The prevalence and incidence of copper deficiency following RYGB surgery was determined to be 9.6% and 18.8%, respectively, with many patients experiencing mild-to-moderate symptoms. Given that copper deficiency can lead to serious and irreversible complications if untreated, frequent monitoring of the copper status of RYGB patients is warranted.
copper deficiency; bariatric surgery; nutritional complications
The intake of a Western diet enriched in animal fat has been shown to be a major risk factor for Type 2 diabetes and obesity. Previous rodent studies have indicated that these conditions may be triggered by the accumulation of the sphingolipid ceramide in insulin-sensitive tissues. However, data are lacking in this regard from both humans and non-human primates.
Here we have investigated the relationship between plasma ceramides and metabolic syndrome in Rhesus macaques fed a high-fat and high-fructose (HFFD) ‘western’ diet.
We investigated this relationship in cohorts of monkeys fed a HFFD for a period of 8 months to 5 years. Animals were classified as control, pre-diabetic or diabetic based on fasting plasma parameters and insulin sensitivity.
HFFD treatment produced significant increases in body weight and body fat and also resulted in a decline in insulin sensitivity. In parallel to the reduction in insulin sensitivity, significant increases in both plasma ceramide and dihydroceramide levels were observed, which further increased as animals progressed to the diabetic state. Plasma levels of the rare sphingolipid C18:0 deoxysphinganine, a marker of increased metabolic flux through serine palmitoyl transferase (SPT), were also elevated in both pre- and diabetic animals. Furthermore, plasma serine levels were significantly elevated in diabetic monkeys, which may indicate a shift in SPT substrate selectivity from serine to alanine or glycine. In contrast, branch chain amino acids were unchanged in pre-diabetic non-human primates, and only plasma valine levels were elevated in diabetic animals.
Together, these data indicate that HFFD induces de novo synthesis of ceramides in non-human primates, and that increased production of plasma ceramides is significantly correlated with the decline in insulin sensitivity.
ceramide; insulin resistance; rhesus monkey
Diets high in fat are implicated in the development and maintenance of obesity, and obese individuals display greater preferences for high-fat foods than do their lean counterparts. Weight-reduction bariatric surgery is associated with changes in food choice. In particular, after Roux-en-Y Gastric Bypass (RYGB), humans and rodents select or prefer foods which are lower in fat content. We asked whether a bariatric surgical procedure limited to the stomach, Vertical Sleeve Gastrectomy (VSG), causes a similar reduction of fat intake/preference.
Research Design and Methods
Rats received VSG or Sham surgery or remained surgically naïve, and were assessed for food preference using three diet-choice paradigms. Using progressive-ratio and conditioned taste aversion paradigms, we further asked whether surgically-induced changes in food choice are secondary to changes in the reward value of food and/or to the formation of a food aversion. Finally, food choice was compared between VSG and RYGB-operated rats.
VSG rats decreased their intake of dietary fat, and shifted their preference toward lower caloric-density foods. This change in food choice was not associated with changes in motivated responding on a progressive-ratio schedule for either a fat or a carbohydrate food reinforcer. When VSG and RYGB were compared directly, both procedures caused comparable changes in food choice. The conditioned taste aversion paradigm revealed that VSG rats form an aversion to an intra-gastric oil administration whereas RYGB rats do not.
VSG and RYGB, two anatomically-distinct bariatric procedures, produce similar changes in food choice.
Bariatric Surgery; Roux-en-Y Gastric Bypass; Macronutrient; Food Reward
To investigate the influence of adiposity on patterns of sex hormones across the menstrual cycle among regularly menstruating women.
The BioCycle Study followed 239 healthy women for 1–2 menstrual cycles, with up to 8 visits per cycle timed using fertility monitors.
Serum estradiol (E2), progesterone, luteinizing hormone (LH), follicle-stimulating hormone (FSH), and sex hormone binding globulin (SHBG) were measured at each visit. Adiposity was measured by anthropometry and by dual energy x-ray absorptiometry. Differences in hormonal patterns by adiposity measures were estimated using nonlinear mixed models, which allow for comparisons in overall mean levels, amplitude (i.e. lowest to highest level within each cycle), and shifts in timing of peaks while adjusting for age, race, energy intake, and physical activity.
Compared to normal weight women (n=154), obese women (BMI≥30 kg/m2, n=25) averaged lower levels of progesterone (−15%, P=0.003), LH (−17%, P=0.01), FSH (−23%, P=0.001) and higher free E2 (+22%, p=0.001) across the cycle. To lesser magnitudes, overweight women (BMI: 25–30, n=60) also exhibited differences in the same directions for mean levels of free E2, FSH, and LH. Obese women experienced greater changes in amplitude of LH (9%, p=0.002), and FSH (8%, p=0.004), but no differences were observed among overweight women. Higher central adiposity by top compared to bottom tertile of trunk-to-leg fat ratio by DXA was associated with lower total E2 (−14%, p=0.005) and FSH (−15%, p=0.001). Peaks in FSH and LH occurred later (~0.5 day) in the cycle among women with greater central adiposity.
Greater total and central adiposity were associated with changes in mean hormone levels. The greater amplitudes observed among obese women suggest compensatory mechanisms at work to maintain hormonal homeostasis. Central adiposity may be more important in influencing timing of hormonal peaks than total adiposity.
adiposity; body mass index; body composition; sex hormones; menstrual cycle; progesterone; estradiol
Stress is associated with increased intake of palatable foods and with weight gain, particularly in overweight women. Stress, food, and body mass index (BMI) have been separately shown to impact amygdala activity. However, it is not known whether stress influences amygdala responses to palatable foods, and whether this response is associated with chronic stress or BMI.
Fourteen overweight and obese women participated in a functional magnetic resonance imaging (fMRI) scan as they consumed a palatable milkshake during script-driven autobiographical guided imagery of stressful and neutral-relaxing scenarios.
We report that a network including insula, somatomotor mouth area, ventral striatum, and thalamus responds to milkshake receipt, but none of these areas are impacted by stress. In contrast, while the left amygdala responds to milkshake irrespective of condition, the right amygdala responds to milkshake only under stressful conditions. Moreover, this right amygdala response is positively associated with basal cortisol levels, an objective measure of chronic stress. We also found a positive relationship between BMI and stress related increased response to milkshake in the orbitofrontal cortex.
These results demonstrate that acute stress potentiates response to food in the right amygdala and orbitofrontal cortex as a function of chronic stress and body weight, respectively. This suggests that the influence of acute stress in potentiating amygdala and OFC responses to food is dependent upon individual factors like BMI and chronic stress. We conclude that BMI and chronic stress play a significant role in brain response to food and in stress-related eating.
Stress potentiates brain response to food in obese with chronic stress; Risk factors for obesity; Obesity and the brain; neuroimaging