Obesity has a complicated metabolic pathology, and defining the underlying mechanisms of obesity requires integrative studies with molecular endpoints. Real time quantitative PCR (RT-qPCR) is a powerful tool that has been widely utilized. However, the importance of using carefully validated reference genes in RT-qPCR seems to be overlooked in obesity-related research. The objective of this study was to select a set of reference genes with stable expressions to be used for RT-qPCR normalization in rats under fasted vs. re-fed and chow vs. high fat diet (HFD) conditions.
Male Long-Evans rats were treated under four conditions, chow/fasted, chow/re-fed, HFD/fasted, and HFD/re-fed. Expression stabilities of the13 candidate reference genes were evaluated in the rat hypothalamus, duodenum, jejunum, and ileum using ReFinder software program. The optimal number of reference genes needed for RT-qPCR analyses was determined using geNorm.
Using geNorm analysis, we found that it was sufficient to use the two most stably expressed genes as references in RT-qPCR analyses for each tissue under specific experimental conditions. Unique subsets of reference genes out of the 13 candidate genes were identified, each of which is specific for one type of rat tissue (hypothalamus, duodenum, jejunum, or ileum) under a different combination of diet and feeding condition.
Our study demonstrates that gene expression levels of reference genes commonly used in obesity-related studies, such as ACTB, or RPS18, are altered by changes in acute or chronic energy status. These findings underline the importance of using reference genes that are stable in expression across experimental conditions when studying the rat hypothalamus and intestine, because these tissues play an integral role in regulation of energy homeostasis. It is our hope that this study will raise awareness among obesity researchers on the essential need for reference gene validation in gene expression studies.
Obesity; reference gene; hypothalamus; intestine; RT-qPCR; rat
The effects of fruits and vegetables in solid vs. beverage forms on human appetite and food intake acutely and over eight weeks, are unclear.
This 21-week, randomised, crossover study assessed appetitive ratings following the inclusion of fruits and vegetables, in solid and beverage form, into the habitual diet of healthy lean (n=15) and overweight/obese (n=19) adults with low customary consumption. The primary acute outcomes were satiation (amount of challenge meal consumed), satiety (latency of subsequent eating event), and dietary compensation after a 400 kcal fruit preload. Ratings of appetite were also obtained before and after 8 weeks of required increased fruit and vegetable consumption (20% estimated energy requirement).
Acutely, overweight/obese participants reported smaller reductions of hunger after consuming the fruit preload in beverage compared to solid form (preload × form × BMI effects, P=0.030). Participants also consumed significantly less of a challenge meal (in both gram and energy) after the ingestion of the solid fruit preload (P<0.005). However, the subsequent meal latency was not significantly different between the solid and the beverage fruit preloads. Total daily energy intake was significantly higher when the obese participants consumed the beverage fruit preload compared to the solid (P<0.001). Daily energy intake was markedly, but not significantly, higher among the lean with the beverage versus solid food-form. Hunger and fullness ratings remained stable when participants consumed fruits and vegetables in solid or beverage form for eight weeks each.
Acute post-ingestive appetitive responses were weaker following consumption of fruits in beverage versus solid food-forms. Consumption of beverage or solid fruit and vegetable food loads for 8 weeks did not chronically alter appetitive responses.
Solid; beverages; fruits; vegetables; appetite
Obesity is a major risk factor for several musculoskeletal conditions that are characterized by an imbalance of tissue remodeling. Adult stem cells are closely associated with the remodeling and potential repair of several mesodermally derived tissues such as fat, bone, and cartilage. We hypothesized that obesity would alter the frequency, proliferation, multipotency, and immunophenotype of adult stem cells from a variety of tissues.
Materials and Methods
Bone marrow-derived mesenchymal stem cells (MSCs), subcutaneous adipose-derived stem cells (sqASCs), and infrapatellar fat pad-derived stem cells (IFP cells) were isolated from lean and high-fat diet induced obese mice, and their cellular properties were examined. To test the hypothesis that changes in stem cell properties were due to the increased systemic levels of free fatty acids (FFAs), we further investigated the effects of FFAs on lean stem cells in vitro.
Obese mice showed a trend toward increased prevalence of MSCs and sqASCs in the stromal tissues. While no significant differences in cell proliferation were observed in vitro, the differentiation potential of all types of stem cells was altered by obesity. MSCs from obese mice demonstrated decreased adipogenic, osteogenic, and chondrogenic potential. Obese sqASCs and IFP cells showed increased adipogenic and osteogenic differentiation, but decreased chondrogenic ability. Obese MSCs also showed decreased CD105 and increased PDGFRα expression, consistent with decreased chondrogenic potential. FFA treatment of lean stem cells significantly altered their multipotency but did not completely recapitulate the properties of obese stem cells.
These findings support the hypothesis that obesity alters the properties of adult stem cells in a manner that depends on the cell source. These effects may be regulated in part by increased levels of FFAs, but may involve other obesity-associated cytokines. These findings contribute to our understanding of mesenchymal tissue remodeling with obesity, as well as the development of autologous stem cell therapies for obese patients.
Mesenchymal Stem Cells; MSC; ASC; Infrapatellar fat pad; Osteoarthritis; Obesity; High-fat diet; Free fatty acids; Cell therapy; Regeneration; Adipose tissue; Adipokines
Abdominal obesity predicts a wide range of adverse health outcomes. Over the past several decades, prevalence of abdominal obesity has increased markedly in industrialized countries like the U.S. No previous analyses, however, have evaluated whether there are birth cohort effects for abdominal obesity. Estimating cohort effects is necessary to forecast future health trends and understand past population-level trends.
This analysis evaluated whether there were birth cohort effects for abdominal obesity for the Silent Generation (born 1925-1945), children of the Great Depression; Baby Boomers (born 1946-1964); or Generation X (born 1965-1980). Cohort effects for prevalence of abdominal obesity were estimated using the median polish method with data collected from the National Health and Nutrition Examination Survey between 1988 and 2008. Respondents were aged 20-74 years.
After taking into account age effects and ubiquitous secular changes, the Silent Generation and Generation X had higher cohort-specific prevalence of abdominal obesity than the Baby Boomers. Effects were more pronounced in women than men.
This work presents a novel finding: evidence that the birth cohorts of the post-World War II Baby Boom appeared to have uniquely low cohort effects on abdominal obesity. The growing prosperity of the post-World-War II U.S. may have exposed the Baby Boom generation to lower levels of psychosocial and socioeconomic stress than previous or subsequent generations. By identifying factors associated with the Baby Boomers’ low cohort-specific sensitivity to the obesogenic environment, the obesity prevention community can identify early-life factors that can protect future generations from excess weight gain.
age-period-cohort; obesity; abdominal obesity; demography; sex differences; United States
With the increasing rates of obesity, many people diet in attempts to lose weight. Since weight loss is seldom maintained in a single effort, weight cycling is a common occurrence. Unfortunately, reports from clinical studies that have attempted to determine the effect of weight cycling on mortality are in disagreement, and to date, no controlled animal study has been performed to assess the impact of weight cycling on longevity. Therefore, our objective was to determine whether weight cycling altered lifespan in mice that experienced repeated weight gain and weight loss throughout their lives.
Male C57BL/6J mice were placed on one of three lifelong diets: a low fat (LF) diet, a high fat (HF) diet, or a cycled diet in which the mice alternated between 4 weeks on the LF diet and 4 weeks on the HF diet. Body weight, body composition, several blood parameters and lifespan were assessed.
Cycling between the HF and LF diet resulted in large fluctuations in body weight and fat mass. These gains and losses corresponded to significant increases and decreases, respectively, in leptin, resistin, GIP, IGF-1, glucose, insulin, and glucose tolerance. Surprisingly, weight cycled mice had no significant difference in lifespan (801±45 days) as compared to LF fed controls (828±74 days), despite being overweight and eating a HF diet for half of their lives. In contrast, the HF fed group experienced a significant decrease in lifespan (544±73days) compared to LF fed controls and cycled mice.
This is the first controlled mouse study to demonstrate the effect of lifelong weight cycling on longevity. The act of repeatedly gaining and losing weight, in itself, did not decrease lifespan and was more beneficial than remaining obese.
weight cycling; weight fluctuation; yo-yo dieting; weight loss; mortality; longevity
Patients with pseudohypoparathyroidism type 1a (PHP-1a) develop early-onset obesity. The abnormality in energy expenditure and/or energy intake responsible for this weight gain is unknown.
The aim of this study was to evaluate energy expenditure in children with PHP-1a compared with obese controls.
We studied 6 obese females with PHP-1a and 17 obese female controls. Patients were recruited from a single academic center.
Resting energy expenditure and thermogenic effect of a high fat meal were measured using whole room indirect calorimetry. Body composition was assessed using whole body dual energy x-ray absorptiometry. Fasting glucose, insulin and hemoglobin A1C were measured.
Children with PHP-1a had decreased resting energy expenditure compared with obese controls (P <0.01). After adjustment for fat free mass, the PHP-1a group’s resting energy expenditure was 346.4 kcals/day less than obese controls (95% CI [−585.5 to −106.9], P <0.01). The thermogenic effect of food, expressed as percent increase in postprandial energy expenditure over resting energy expenditure, was lower in PHP-1a patients than obese controls but did not reach statistical significance (absolute reduction of 5.9%, 95% CI [−12.2% to 0.3%], P = 0.06).
Our data indicate that children with PHP-1a have decreased resting energy expenditure compared with obese controls and that may contribute to the development of obesity in these children. These patients may also have abnormal diet-induced thermogenesis in response to a high fat meal. Understanding the causes of obesity in PHP-1a may allow for targeted nutritional or pharmacologic treatments in the future.
Pseudohypoparathyroidism; Obesity; Pediatrics; Energy Expenditure
To explore appetite-related hormones following stress in overweight individuals, and their interaction with Night Eating (NE) status.
We measured plasma cortisol and ghrelin concentrations, and recorded ratings of stress and hunger in response to a physiological laboratory stressor (Cold Pressor Test, CPT) in overweight women with (n=11; NE) and without (n=17; non-NE) night eating.
Following the CPT, cortisol (p < .001) and ghrelin (p < .05) levels increased, as did stress and hunger ratings (all p < .001), across all subjects (NE and non-NE). NE exhibited higher baseline cortisol (p < .05) levels than non-NE. NE also had greater cortisol area under the curve (AUC) than non-NE (p = .019), but not when controlling for baseline cortisol levels. Ghrelin baseline and AUC did not differ between groups. NE showed higher AUC stress (p < .05), even when controlling for baseline stress.
Overweight individuals showed increased cortisol, ghrelin, stress and hunger following a laboratory stressor, and there was some evidence for greater increases in cortisol and subjective stress among NE. The greater AUC cortisol in NE was due to higher baseline levels but the group difference in stress was in direct response to the CPT stressor. Our results support a role for cortisol and stress in Night Eating.
eating disorders; HPA axis; sleep; circadian; appetite hormones; gut peptides
A rat model of diet-induced obesity (DIO) was used to determine dopamine transporter (DAT) function, impulsivity and motivation as neurobehavioral outcomes and predictors of obesity.
To evaluate neurobehavioral alterations following the development of DIO induced by an 8-week high-fat diet (HF) exposure, striatal D2-receptor density, DAT function and expression, extracellular dopamine concentrations, impulsivity, and motivation for high- and low-fat reinforcers were determined. To determine predictors of DIO, neurobehavioral antecedents including impulsivity, motivation for high-fat reinforcers, DAT function and extracellular dopamine were evaluated before the 8-week HF exposure.
Striatal D2-receptor density was determined by in vitro kinetic analysis of [3H]raclopride binding. DAT function was determined using in vitro kinetic analysis of [3H]dopamine uptake, methamphetamine-evoked [3H]dopamine overflow and no-net flux in vivo microdialysis. DAT cell-surface expression was determined using biotinylation and western blotting. Impulsivity and food-motivated behavior were determined using a delay discounting task and progressive ratio schedule, respectively.
Relative to obesity-resistant (OR) rats, obesity-prone (OP) rats exhibited 18% greater body weight following an 8-week HF-diet exposure, 42% lower striatal D2-receptor density, 30% lower total DAT expression, 40% lower in vitro and in vivo DAT function, 45% greater extracellular dopamine and twofold greater methamphetamine-evoked [3H]dopamine overflow. OP rats exhibited higher motivation for food, and surprisingly, were less impulsive relative to OR rats. Impulsivity, in vivo DAT function and extracellular dopamine concentration did not predict DIO. Importantly, motivation for high-fat reinforcers predicted the development of DIO.
Human studies are limited by their ability to determine if impulsivity, motivation and DAT function are causes or consequences of DIO. The current animal model shows that motivation for high-fat food, but not impulsive behavior, predicts the development of obesity, whereas decreases in striatal DAT function are exhibited only after the development of obesity.
diet-induced obesity; dopamine transporter; impulsivity; motivation; striatum
Obesity is associated to high insulin and glucagon plasma levels. Enhanced β–cell function and β–cell expansion are responsible for insulin hypersecretion. It is unknown whether hyperglucagonemia is due to α-cell hypersecretion or to an increase in α-cell mass. In this study, we investigated the dynamics of the β-cell and α-cell function and mass in pancreas of obese normoglycemic baboons.
Pancreatic β- and α-cell volumes were measured in 51 normoglycemic baboons divided into 6 groups according to overweight severity or duration. Islets morphometric parameters were correlated to overweight and to diverse metabolic and laboratory parameters.
Relative α-cell volume (RαV) and relative islet α-cell volume (RIαV) increased significantly with both overweight duration and severity. Conversely, in spite of the induction of insulin resistance, overweight produced only modest effects on relative β-cell volume (RβV) and relative islet β-cell volume (RIβV). Of note, RIβV did not increase neither with overweight duration nor with overweight severity, supposedly because of the concomitant, greater, increase in RIαV. Baboons' body weights correlated with serum levels of Interleukin-6 and Tumour Necrosis Factor-α soluble Receptors (IL-6sR and sTNF-R1), demonstrating that overweight induces abnormal activation of the signaling of two cytokines known to impact differently β- and α-cell viability and replication.
In conclusion, overweight and insulin resistance induce in baboons a significant increase in α-cell volumes (RαV, RIαV) while have minimal effects on the β-cells. This study suggests that an increase in the α-cell mass may precede the loss of β-cells and the transition to overt hyperglycemia and diabetes.
Obesity duration; obesity severity; α-cell volume; β-cells volume; pancreatic islet remodelling; insulin resistance
To investigate the role of toddlers’ self-regulation skills and temperament in predicting weight outcomes in preadolescence.
Participants for this study included 195 children (114 girls) obtained from three different cohorts participating in a larger ongoing longitudinal study. At 2 years of age, participants participated in several laboratory tasks designed to assess their self-regulation abilities, including emotion regulation, sustained attention, and delay of gratification, while parents filled out a temperament questionnaire to assess toddlers’ pleasure expression. Height and weight measures were collected when children were 4, 5, 7, and 10 years of age. Children also filled out a body image and eating questionnaire at the 10 year visit.
Self-regulation skills in toddlers were associated with both BMI development, pediatric obesity, and body image/eating concerns. The temperament dimension of pleasure was also associated with BMI development and pediatric obesity but not body image/eating concerns.
Self-regulation difficulties across domains as well as temperament based pleasure in toddlers represented significant individual risk factors for the development of pediatric obesity eight years later. Early self-regulation difficulties also contributed to body image and eating concerns that typically accompanied overweight children. The mechanisms by which early self-regulation skills and temperament based pleasure may contribute to the development of pediatric obesity and associated weight concerns are discussed.
pediatric obesity; BMI; body image; self-regulation; toddlerhood; preadolescence
To determine the association between accelerometry-derived sedentary behavior and body mass index (BMI) z-score in preschool children and to determine whether the association changed when applying three different accelerometry cutpoints for sedentary behavior.
DESIGN AND SUBJECTS
Cross-sectional design. Data came from two completed studies: Children’s Activity and Movement in Preschool Study (CHAMPS) and the Environmental Determinants of Physical Activity in Preschool Children (EDPAPC) study. Children ages 3 to 5 with complete data on sedentary behavior, BMI z-score, physical activity, and other covariates were included in the analyses (N = 263 in CHAMPS and N = 155 in EDPAPC). Accelerometry data were summarized as time spent in sedentary behavior (min/hr) using three different cutpoints developed specifically for preschool children (< 37.5, <200, and <373 counts/15 seconds). Linear mixed regression models were used to determine the association between time spent in sedentary behavior and BMI z-score; age, gender, race, parental education, preschools, and moderate-to-vigorous physical activity (MVPA) were included as covariates.
In both CHAMPS and EDPAPC study, no independent association between time spent in sedentary behavior and BMI z-score was observed after adjusting for MVPA. The observed null association between sedentary behavior and BMI z-score was maintained even with different sedentary behavior cutpoints.
Regardless of cutpoints used, accelerometry-derived sedentary behavior was not independently associated with BMI z-score in two independent samples of preschool children. Longitudinal studies addressing this research question are needed.
Accelerometer; preschool; sedentary behavior; BMI
The expanding overweight and obesity epidemic notwithstanding, little is known about their long-term effect on health-related quality of life (HRQoL). The main objective of this study was to investigate whether overweight (body mass index [BMI] 25–<30 kg/m2) and obese (BMI ≥ 30 kg/m2) young adults have poorer HRQoL 20 years later.
The authors studied 3014 participants in the Coronary Artery Risk Development in Young Adults (CARDIA) study, a longitudinal, community-dwelling, biracial cohort from four cities. BMI was measured at baseline and 20 years later. HRQoL was assessed via the physical component summary (PCS) and the mental component summary (MCS) scores of the Medical Outcomes Study 12-Item Short Form Health Survey at year 20. Higher PCS or MCS scores indicate better HRQoL.
Mean year 20 PCS score was 52.2 for normal weight participants at baseline, 50.3 for overweight, and 46.4 for obese (P-trend <0.001). This relation persisted after adjustment for baseline demographics, general health, and physical and behavioral risk factors and after further adjustment for 20-year changes in risk factors. No association was observed for MCS scores (P-trend 0.43).
Overweight and obesity in early adulthood are adversely associated with self-reported physical HRQoL, but not mental HRQoL 20 years later.
Previous data indicate a rapidly increasing prevalence of obesity and overweight among English children and an emerging socioeconomic gradient in prevalence. The main aim of this study was to update prevalence trends among school-age children and assess the changing socioeconomic gradient.
A series of nationally representative household-based health surveys conducted between 1997 and 2007 in England.
15,271 white children (7880 boys) aged 5 to 10 years with measured height and weight.
Height and weight were directly measured by trained fieldworkers. Overweight (including obesity) and obesity prevalence were calculated using the international body mass index cut-offs. Socioeconomic position (SEP) score was a composite score based on income and social class. Multiple linear regression assessed the prevalence odds with time point (1997/8, 2000/1, 2002/3, 2004/5, 2006/7) as the main exposure. Linear interaction terms of time by SEP were also tested for.
There are signs that the overweight and obesity trend has levelled off from 2002/3 to 2006/7. The odds ratio (OR) for overweight in 2006/7 compared to 2002/3 was 0.99 (95% CI 0.88 to 1.11) and for obesity OR = 1.06 (0.86 to 1.29). The socioeconomic gradient has increased in recent years, particularly 2006/7. Compared to 1997/8, the 2006/7 age and sex-adjusted OR for overweight was 1.88 (1.52 to 2.33) in low SEP, 1.25 (1.04 to 1.50) in middle SEP, and 1.13 (0.86 to 1.48) in high SEP children.
Childhood obesity and overweight prevalence among school-age children in England has stabilised in recent years, but children from lower socio-economic strata have not benefited from this trend. There is an urgent need to reduce socio-economic disparities in childhood overweight and obesity.
Obesity; overweight; children; trends; England; socioeconomic status; socioeconomic position; income
The skeletal muscle of obese humans is characterized by an inability to appropriately respond to alterations in substrate availability. The purpose of the current study was to determine if this metabolic inflexibility with obesity is retained in mitochondria of human skeletal muscle cells raised in culture (HSkMC) and to identify potential mechanisms involved.
Mitochondrial respiration was measured in permeabilized myotubes cultured from lean and obese individuals before and after a 24 h lipid incubation.
Mitochondrial respiration (State 3) in the presence of lipid substrate (palmitoyl carnitine) increased by almost 2-fold after lipid incubation in HSkMC from lean, but not obese subjects, indicative of metabolic inflexibility with obesity. The 24 h lipid incubation increased mitochondrial DNA (mtDNA) copy number in HSkMC from lean subjects by +16% (P<0.05); conversely, mtDNA copy number decreased in myotubes cultured from obese individuals (−13%, P=0.06). When respiration data were normalized to mtDNA copy number and other indices of mitochondrial content (COX-IV protein content and CS activity), the significant treatment effects of lipid incubationpersisted in the lean subjects, suggesting concomitant alterations in mitochondrial function; no similar adjustment was evident in HSkMC from obese individuals.
These data indicate that the skeletal muscle of obese individuals inherently lacks metabolic flexibility in response to lipid exposure, which consists of an inability to increase mitochondrial respiration in the presence of lipid substrate and perhaps by an inability to induce mitochondrial proliferation.
Skeletal Muscle; Lipid Oxidation; Mitochondria
Considerable evidence suggests that the time of day at which calories are consumed markedly impacts body weight gain and adiposity. However, a precise quantification of energy balance parameters during controlled animal studies enforcing time-of-day-restricted feeding is currently lacking in the absence of direct human interaction.
The purpose of the present study was therefore to quantify the effects of restricted feeding during the light (sleep) phase in a fully-automated, computer-controlled comprehensive laboratory animal monitoring system (CLAMS) designed to modulate food access in a time-of-day-dependent manner. Energy balance, gene expression (within metabolically-relevant tissues), humoral factors, and body weight were assessed.
We report that relative to mice fed only during the dark (active) phase, light (sleep) phase fed mice: 1) consume a large meal upon initiation of food availability; 2) consume greater total calories per day; 3) exhibit a higher RER (indicative of decreased reliance on lipid/fatty acid oxidation); 4) exhibit tissue-specific alterations in the phases and amplitudes of circadian clock and metabolic genes in metabolically active tissues (greatest phase differences observed in the liver, and diminution of amplitudes in epididymal fat, gastrocnemius muscle, and heart); 5) exhibit diminished amplitude in humoral factor diurnal variations (e.g., corticosterone); and 6) exhibit greater weight gain within 9 days of restricted feeding.
Collectively, these data suggest that weight gain following light (sleep) phase restricted feeding is associated with significant alterations in energy balance, as well as dyssynchrony between metabolically active organs.
Body Weight; Chronobiology; Energy Balance; Gene Expression; Metabolism
The directional and temporal nature of relationships between overweight and obesity and hysterectomy with or without oophorectomy is not well understood. Overweight and obesity may be both a risk factor for the indications for these surgeries and a possible consequence of the procedure. We used prospective data to examine whether body mass index (BMI) increased more following hysterectomy with and without bilateral oophorectomy compared to natural menopause among middle-aged women.
BMI was assessed annually for up to 10 years in the Study of Women’s Health Across the Nation (SWAN (n=1962). Piecewise linear mixed growth models were used to examine changes in BMI before and after natural menopause, hysterectomy with ovarian conservation, and hysterectomy with bilateral oophorectomy. Covariates included education, race/ethnicity, menopausal status, physical activity, self-rated health, hormone therapy use, antidepressant use, and age the visit prior to the final menstrual period (FMP; for natural menopause) or surgery (for hysterectomy/oophorectomy).
By visit 10, 1780 (90.6%) women reached natural menopause, 106 (5.5%) reported hysterectomy with bilateral oophorectomy, and 76 (3.9%) reported hysterectomy with ovarian conservation. In fully adjusted models, BMI increased for all women from baseline to FMP or surgery (annual rate of change=.19 kg/m2 per year), with no significant differences in BMI change between groups. BMI also increased for all women following FMP, but increased more rapidly in women following hysterectomy with bilateral oophorectomy (annual rate of change=.21 kg/m2 per year) as compared to following natural menopause (annual rate of change=.08 kg/m2 per year, p=.03).
In this prospective examination, hysterectomy with bilateral oophorectomy was associated with greater increases in BMI in the years following surgery than following hysterectomy with ovarian conservation or natural menopause. This suggests that accelerated weight gain follows bilateral oophorectomy among women in midlife, which may increase risk for obesity-related chronic diseases.
menopause; oophorectomy; BMI; women’s health
To assess whether sleep apnea severity has an independent relationship with leptin levels in blood after adjusting for different measures of obesity and whether the relationship between OSA severity and leptin levels differs depending on obesity level.
Cross-sectional study of 452 untreated obstructive sleep apnea (OSA) patients (377 males and 75 females), in the Icelandic Sleep Apnea Cohort (ISAC), age 54.3±10.6 (mean±SD), BMI 32.7±5.3 kg/m2 and apnea-hypopnea index (AHI) 40.2 ± 16.1 events/hour. A sleep study and magnetic resonance imaging of abdominal visceral and subcutaneous fat volume were performed as well as fasting serum morning leptin levels measured.
Leptin levels were more highly correlated with body mass index (BMI), total abdominal and subcutaneous fat volume than visceral fat volume per se. No relationship was found between sleep apnea severity and leptin levels, assessed within three BMI groups (BMI<30, BMI 30–35 and BMI>35 kg/m2). In a multiple linear regression model, adjusted for gender, BMI explained 38.7% of the variance in leptin levels, gender explained 21.2% but OSA severity did not have a significant role and no interaction was found between OSA severity and BMI on leptin levels. However, hypertension had a significant effect on the interaction between OSA severity and obesity (p=0.04). In post-hoc analysis for nonhypertensive OSA subjects (n=249), the association between leptin levels and OSA severity explained a minor but significant variance (3.2%) in leptin levels. This relationship was greatest for nonobese nonhypertensive subjects (significant interaction with obesity level). No relationship of OSA severity and leptin levels was found for hypertensive subjects (n=199).
Obesity and gender are the dominant determinants of leptin levels. OSA severity is not related to leptin levels except to a minor degree in nonhypertensive nonobese OSA subjects.
Obstructive sleep apnea; leptin; visceral fat; subcutaneous fat; obesity; hypertension
High-fat diets result in increased body weight. However, this is not uniform and determining the factors that make some animals or individual more susceptible to this diet-induced weight gain is a critical research question. The expansion of white adipose tissue (WAT) associated with weight gain requires high rates of angiogenesis to support the expanding tissue mass. We hypothesized that diet-induced obese (DIO) mice have a greater capacity for WAT angiogenesis and remodeling than diet-resistant (DR) mice at a young age, prior to age or diet-induced obesity.
We measured body weight and body composition by NMR. We compared the expression of genes related to lipid metabolism, angiogenesis and inflammation by RT-qPCR and PCR arrays. WAT morphology and distribution of adipocyte size were analyzed. The level of hypoxia and vascular density was assessed by immunohistochemistry in WAT of young mice.
C57Bl/6 mice were DIO and FVB/N mice DR after 8 weeks on a low fat diet or high fat diet (HFD). However, C57Bl/6 mice had lower body weight, lower adiposity, smaller adipocytes and decreased leptin and lipogenic genes expression in AT than FVB/N mice at 9 weeks of age on a chow diet. Despite having smaller adipocytes, the level of hypoxia and the expression of pro-angiogenesis genes were higher in WAT of young C57Bl/6 mice than young FVB/N mice. In addition, expression of genes related to macrophages and their recruitment, and to proinflammatory cytokines, was significantly higher in WAT of young C57Bl/6 mice than young FVB/N mice.
These data suggest that the potential for WAT remodeling in early period of growth is higher in C57Bl/6 mice as compared to FVB/N mice and we hypothesize that it may contribute to the increased susceptibility to DIO of C57Bl/6 mice.
adipose tissue; angiogenesis; inflammation; hypoxia; diet-induced obesity; diet-resistant; body weight; high-fat diet
The pathogenesis of obesity remains incompletely understood. Drosophila have conserved neuroendocrine and digestion systems with human and become an excellent system for studying energy homeostasis. Here, we reported a novel obesity Drosophila model, in which expression of human protein, synphilin-1 (SP1), in neurons fosters positive energy balance.
SUBJECTS AND METHODS
To further understand the actions of SP1 in energy balance control, the upstream activation sequence UAS/GAL4 system was used to generate human SP1 transgenic Drosophila. We characterized a human SP1 transgenic Drosophila by assessing SP1 expression, fat lipid deposition, food intake and fly locomotor activity to determine the major behavioral changes and their consequences in the development of the obesity-like phenotype.
Overexpression of SP1 in neurons, but not peripheral cells, increased the body weight of flies compared with that of non-transgenic controls. SP1 increased food intake but did not affect locomotor activity. SP1 increased the levels of triacylglycerol, and the size of fat body cells and lipid droplets, indicating that SP1 increased lipid-fat disposition. Survival studies showed that SP1 transgenic flies were more resistant to food deprivation. SP1 regulated lipin gene expression that may participate in SP1-induced fat deposition and starvation resistance.
These studies demonstrate that SP1 expression affects energy homeostasis in ways that enhance positive energy balance and provide a useful obesity model for future pathogenesis and therapeutic studies.
Synphilin-1; fat disposition; transgenic Drosophila; lipin
Humans have an innate requirement for sleep that is intrinsically governed by circadian and endocrine systems. More recently, reduced sleep duration has gained significant attention for its possible contribution to metabolic dysfunction. Significant evidence suggests that reduced sleep duration may elevate the risk for impaired glucose functioning, insulin resistance and type 2 diabetes. However, to date, few studies have determined the implications of reduced sleep duration with regard to glucose control during pregnancy. With the high prevalence of overweight and obesity in women of reproductive age, the occurrence of gestational diabetes mellitus (GDM) is increasing. GDM results in elevated risk of maternal and fetal complications, as well as increased risk of type 2 diabetes postpartum. Infants born to women with GDM also carry a life-long risk of obesity and type 2 diabetes. The impact of reduced sleep on glucose management during pregnancy has not yet been fully assessed and a paucity of literature currently exits. Herein, we review the association between reduced sleep and impaired carbohydrate metabolism and propose how reduced sleep during pregnancy may result in further dysfunction of the carbohydrate axis. A particular focus will be given to sleep-disordered breathing, as well as GDM-complicated pregnancies. Putative mechanisms of action by which reduced sleep may adversely affect maternal and infant outcomes are also discussed. Finally, we will outline important research questions that need to be addressed.
sleep; sleep-disordered breathing; pregnancy; gestational diabetes
We aimed to investigate whether vitamin D supplementation modulates peripheral blood mononuclear cell telomerase activity in overweight African Americans.
A double blind, randomized, and placebo-controlled clinical trial (#NCT01141192) was recently conducted.
Subjects and methods
African American adults were randomly assigned to either the placebo, or the vitamin D group (60,000 IU/month [equivalent to ~2,000 IU/day] oral vitamin D3 supplementation). Fresh peripheral blood mononuclear cells (PBMC) were collected from 37 subjects (18 in the placebo group and 19 in the vitamin D group) both at baseline and 16 weeks. PBMC telomerase activity was measured by the telomeric repeat amplification protocol.
Serum 25 hydroxyvitamin D levels increased from 40.7±15.7 nmol/L at baseline to 48.1±17.5 nmol/L at posttest (p=0.004) in the placebo group, and from 35.4±11.3 nmol/L at baseline to 103.7±31.5 nmol/L posttests (p<0.0001) in the vitamin D group. In the vitamin D group, PBMC telomerase activity increased by 19.2% from baseline (1.56±0.29 AU) to posttest (1.86±0.42 AU, p<0.0001). The significance persisted after controlling for age, sex and body mass index (p=0.039). PBMC telomerase activity in the placebo group did not change from baseline (1.43±0.26 AU) to posttest (1.46±0.27 AU, p=0.157).
Vitamin D supplementation significantly increased PBMC telomerase activity in overweight African Americans. Our data suggest that vitamin D may improve telomere maintenance and prevent cell senescence and counteract obesity-induced acceleration of cellular aging.
vitamin D supplementation; telomerase activity; 25(OH)D; obesity; African Americans
All available treatments directed towards obesity and obesity-related complications are associated with suboptimal effectiveness/invasiveness ratios. Pharmacological, behavioral and lifestyle modification treatments are the least invasive, but also the least effective options, leading to modest weight loss that is difficult to maintain long-term. Gastrointestinal weight loss surgery (GIWLS) is the most effective, leading to >60–70% of excess body weight loss, but also the most invasive treatment available. Sleeve gastrectomy (SGx) and Roux-en-Y gastric bypass (RYGB) are the two most commonly performed GIWLS procedures. The fundamental anatomic difference between SGx and RYGB is that in the former procedure, only the anatomy of the stomach is altered, without surgical reconfiguration of the intestine. Therefore, comparing these two operations provides a unique opportunity to study the ways that different parts of the gastrointestinal (GI) tract contribute to the regulation of physiological processes, such as the regulation of body weight, food intake and metabolism.
To explore the physiologic mechanisms of the two procedures, we used rodent models of SGx and RYGB to study the effects of these procedures on body weight, food intake and metabolic function.
Both SGx and RYGB induced a significant weight loss that was sustained over the entire study period. SGx-induced weight loss was slightly lower compared with that observed after RYGB. SGx-induced weight loss primarily resulted from a substantial decrease in food intake and a small increase in locomotor activity. In contrast, rats that underwent RYGB exhibited a substantial increase in non-activity-related (resting) energy expenditure and a modest decrease in nutrient absorption. Additionally, while SGx-treated animals retained their preoperative food preferences, RYGB-treated rats experienced a significant alteration in their food preferences.
These results indicate a fundamental difference in the mechanisms of weight loss between SGx and RYGB, suggesting that the manipulation of different parts of the GI tract may lead to different physiologic effects. Understanding the differences in the physiologic mechanisms of action of these effective treatment options could help us develop less invasive new treatments against obesity and obesity-related complications.
gastric bypass; metabolism; metabolic surgery; energy expenditure; animal models; sleeve gastrectomy
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