Description

Formerly known as Obesity Research, Obesity is the official journal of The Obesity Society. Available in print and online, Obesity is dedicated to increasing knowledge, fostering research, and promoting better treatment for people with obesity and their loved ones. Obesity publishes important peer-reviewed research and cutting-edge reviews, commentaries, public health and medical developments.

Publisher details

Nature Publishing Group

Publications in this journal

• Effects of oral and gastric stimulation on appetite and energy intake.

  Authors: A Wijlens, A Erkner, E Alexander, M Mars, P A M Smeets, C de Graaf

  Obesity (Silver Spring, Md.).

  Appetite is regulated by many factors, including oro-sensory and gastric signals. There are many studies on contributions of and possible interaction between sensory and gastric stimulation, butAppetite is regulated by many factors, including oro-sensory and gastric signals. There are many studies on contributions of and possible interaction between sensory and gastric stimulation, but there are few studies in humans using simultaneous oral and gastric stimulation. We investigated the effect of simultaneous, but independently manipulated, oral and gastric stimulation on appetite ratings and energy intake. We hypothesized that compared with no stimulation, oral and gastric stimulation would equally and additively decrease appetite ratings and energy intake.Healthy men (n=26, 21±2 y, BMI 22±3 kg/m(2)) participated in a randomized cross-over trial with four experimental conditions and a control condition. Experimental conditions consisted of oral stimulation, with either 1 or 8 min modified sham feeding, and gastric stimulation, with either 100 or 800 mL intragastrically infused liquid (isocaloric, 99 kcal, 100 mL/min). The control condition consisted of no oral or gastric stimulation. Outcome measures were energy intake 30 minutes after the treatment and appetite ratings. Compared with the control condition, energy intake decreased significantly after the 8min/100mL (19% lower, P=0.001) and 8min/800mL conditions (15% lower, P=0.02), but not after the 1min/100mL (14% lower, P=0.06) and 1min/800mL conditions (10% lower, P=0.39). There was no interaction of oral and gastric stimulation on energy intake. Hunger and fullness differed across all conditions (P≤0.01).In conclusion, duration of oral exposure was at least as important in decreasing energy intake as gastric filling volume. Oral and gastric stimulation did not additively decrease energy intake. Longer oro-sensory stimulation, therefore, may be an important contributor to a lower energy intake.

• EVALUATION OF OXIDATIVE STRESS IN OVERWEIGHT SUBJECTS WITH OR WITHOUT METABOLIC SYNDROME.

  Authors: Danielle Venturini, Andréa N C Simão, Nicole A Scripes, Larissa D Bahls, Petrônio A S Melo, Francine M Belinetti, Marcell A B Lozovoy, Isaias Dichi

  Obesity (Silver Spring, Md.).

  Although oxidative stress is considered the underlying mechanism by which dysfunctional metabolism occurs in obese subjects, there are few studies on oxidative stress in overweight subjects. TheAlthough oxidative stress is considered the underlying mechanism by which dysfunctional metabolism occurs in obese subjects, there are few studies on oxidative stress in overweight subjects. The objective of this study was to verify the influence of metabolic syndrome (MetS) on oxidative stress and antioxidant defense in overweight subjects. There were 123 subjects (50 in the control group and 73 in the overweight group) chosen to participate in this cross-sectional study. The control group included 50 healthy individuals with a body mass index (BMI) between 20 and 24.9 kg/m(2) and without MetS. The overweight group included 73 subjects with a BMI between 25 and 29.9 kg/m(2). Overweight subjects were divided into two groups: with MetS (29 subjects) and without MetS (44 subjects). Control group and overweight group subjects without MetS showed no differences in oxidative stress parameters and total antioxidant capacity (TRAP). Overweight subjects with MetS had higher hydroperoxide concentrations measured by chemiluminescence compared to the control group (p < 0.05), higher hydroperoxide and hydrogen peroxide concentrations determined by ferrous oxidation-xylenol orange assay compared to overweight subjects without MetS (p < 0.001), and higher advanced oxidation protein product (AOPP) concentrations (p < 0.001) compared to the other groups. AOPP was directly correlated with uric acid concentrations. Overweight subjects with MetS had lower TRAP concentrations compared to the control group (p < 0.001). In conclusion, this study showed that overweight subjects with MetS, in contrast to overweight subjects without MetS, have a redox imbalance characterized by increased plasma oxidation and reduced antioxidant capacity.

• Brain response to food stimulation in obese, normal weight, and successful weight loss maintainers.

  Authors: Lawrence H Sweet, Jason J Hassenstab, Jeanne M McCaffery, Hollie A Raynor, Dale S Bond, Kathryn E Demos, Andreana P Haley, Ronald A Cohen, Angelo Del Parigi, Rena R Wing

  Obesity (Silver Spring, Md.).

  As many people struggle with maintenance of weight loss, the study of successful weight loss maintainers (SWLM) can yield important insights into factors contributing to weight loss maintenance.As many people struggle with maintenance of weight loss, the study of successful weight loss maintainers (SWLM) can yield important insights into factors contributing to weight loss maintenance. However, little research has examined how SWLM differ from people who are obese or normal weight (NW) in brain response to orosensory stimulation. The goal of this study was to determine if SWLM exhibit different brain responses to orosensory stimulation. Brain response to one-minute orosensory stimulation with a lemon lollipop was assessed using functional magnetic resonance imaging (FMRI) among 49 participants, including SWLM (n=17), NW (n=18) and obese (n=14) controls. Significant brain responses were observed in nine brain regions, including the bilateral insula, left inferior frontal gyrus, left putamen, and other sensory regions. All regions also exhibited significant attenuation of this response over one minute. The SWLM exhibited greater response compared to the other groups in all brain regions. Findings suggest that the response to orosensory stimulation peaks within 40 seconds and attenuates significantly between 40-60 seconds in regions associated with sensation, reward, and inhibitory control. Greater reactivity among the SWLM suggests that greater sensory reactivity to orosensory stimulation, increased anticipated reward, and subsequently greater inhibitory processing are associated with weight loss maintenance.

• Improved arteriole-to-venule ratio of retinal vessels resulting from bariatric surgery.

  Authors: Alexander Lammert, Till Hasenberg, Caroline Kräupner, Peter Schnülle, Hans-Peter Hammes

  Obesity (Silver Spring, Md.).

  Obesity causes increased morbidity and mortality from metabolic and cardiovascular disease. We investigated the effect of bariatric surgery on endothelial dysfunction in retinal vessels as a markerObesity causes increased morbidity and mortality from metabolic and cardiovascular disease. We investigated the effect of bariatric surgery on endothelial dysfunction in retinal vessels as a marker of metabolic and cardiovascular risk in patients with obesity WHO III°.Thirty consecutive patients (19/11, w/m) were evaluated by anthropometry, lipid profile, and oral glucose tolerance test before and after bariatric surgery (Mannheim Obesity Study MOS; NCT 00770276). Risk stratification was performed by the presence of metabolic syndrome (MetS) according to ATP-III. Subclinical atherosclerosis was assessed by measurement of intima media thickness (IMT). Flicker light response of retinal vessels was used as measures of endothelial dysfunction (ED). We measured their arteriole-to-venule ratio (AVR) for evaluation of vascular pathology. After a median of 9 months following bariatric surgery, mean weight loss was 39.4 kg (37.3%). Remission of impaired glucose metabolism was achieved in 53.3% of affected patients. Dyslipidemia improved significantly (triglycerides -61.3 mg/dl, p<0.0001, total cholesterol - 28.2 mg/dl, p=0.002 and LDL-cholesterol were reduced -24.5 mg/dl, p=0.008). This resulted in a significant reduction of patients classified for MetS (27 vs. 9, p<0.0001). Adiponectin increased by 2.08 µg/l (p=0.032) and hs-CRP and sICAM decreased (-7.3 mg/l, p<0.0001 and -146.4 ng/ml, p=0.0006). AVR improved significantly (+0.04, p<0.0001), but neither Flicker light response nor IMT changed significantly. Retinal AVR is ameliorated after bariatric intervention. As an increased AVR results from either or both widening retinal arteriolar caliber and narrowing retinal venular caliber, an improvement in small vessel profile is evident 9 months after bariatric surgery.

• The Relation of Adiposity to Cognitive Control and Scholastic Achievement in Preadolescent Children.

  Authors: Keita Kamijo, Naiman A Khan, Matthew B Pontifex, Mark R Scudder, Eric S Drollette, Lauren B Raine, Ellen M Evans, Darla M Castelli, Charles H Hillman

  Obesity (Silver Spring, Md.).

  Adiposity may be negatively associated with cognitive function in children. However, the findings remain controversial, in part due to the multifaceted nature of cognition and perhaps the lack ofAdiposity may be negatively associated with cognitive function in children. However, the findings remain controversial, in part due to the multifaceted nature of cognition and perhaps the lack of accurate assessment of adiposity. The aim of this study was to clarify the relation of weight status to cognition in preadolescent children using a comprehensive assessment of cognitive control, academic achievement, and measures of adiposity. Preadolescent children between 7 and 9 years (n = 126) completed Go and NoGo tasks, as well as the Wide Range Achievement Test 3rd edition (WRAT3), which measures achievement in reading, spelling, and arithmetic. In addition to body mass index (BMI), fat mass was measured using dual X-ray absorptiometry (DXA). Data were analyzed with multiple regression analysis, controlling for confounding variables. Analyses revealed that BMI and fat mass measured via DXA were negatively associated with cognitive control, as children with higher BMI and fat mass exhibited poorer performance on the NoGo task requiring extensive amounts of inhibitory control. By contrast, no relation of weight status to performance was observed for the Go task requiring smaller amounts of cognitive control. Higher BMI and fat mass were also associated with lower academic achievement scores assessed on the WRAT3. These data suggest that adiposity is negatively and selectively associated with cognitive control in preadolescent children. Given that cognitive control has been implicated in academic achievement, the present study provides an empirical basis for the negative relationship between adiposity and scholastic performance.

• The microbiota of the gut in preschool children with normal and excessive body weight.

  Authors: Caroline L J Karlsson, Jenny Onnerfält, Jie Xu, Göran Molin, Siv Ahrné, Kristina Thorngren-Jerneck

  Obesity (Silver Spring, Md.).

  The aim of this study was to investigate the gut microbiota in preschool children with and without overweight and obesity. Twenty overweight or obese children and twenty children with body mass indexThe aim of this study was to investigate the gut microbiota in preschool children with and without overweight and obesity. Twenty overweight or obese children and twenty children with body mass index within the normal range (age: 4-5 years) were recruited from the south of Sweden. The gut microbiota was accessed by quantitative polymerase chain reactions and terminal restriction fragment length polymorphism and calprotectin was measured in faeces. Liver enzymes were quantified in obese/overweight children. The concentration of the Gram-negative family Enterobacteriaceae was significantly higher in the obese/overweight children (P=0.036) while levels of Desulfovibrio and Akkermansia muciniphila-like bacteria were significantly lower in the obese/overweight children (P=0.027 and P=0.030, respectively). No significant differences were found in content of Lactobacillus, Bifidobacterium or the Bacteroides fragilis group. The diversity of the dominating bacterial community tended to be less diverse in the obese/overweight group, but the difference was not statistically significant. Concentration of Bifidobacterium was inversely correlated to alanine aminotransferase in obese/overweight children. The faecal levels of calprotectin did not differ between the study groups. These findings indicate that the gut microbiota differed among preschool children with obesity/overweight compared with children with body mass index within the normal range.

• Associations of Testosterone and Sex Hormone Binding Globulin with Adipose Tissue Hormones in Midlife Women.

  Authors: R P Wildman, D Wang, I Fernandez, P Mancuso, N Santoro, P E Scherer, M R Sowers

  Obesity (Silver Spring, Md.).

  Regulators of adipose tissue hormones remain incompletely understood, but may include sex hormones. As adipose tissue hormones have been shown to contribute to numerous metabolic and cardiovascularRegulators of adipose tissue hormones remain incompletely understood, but may include sex hormones. As adipose tissue hormones have been shown to contribute to numerous metabolic and cardiovascular disorders, understanding their regulation in midlife women is of clinical importance. Therefore, we assessed the associations between testosterone (T) and sex hormone binding globulin (SHBG) with leptin, high molecular weight (HMW) adiponectin, and the soluble form of the leptin receptor (sOB-R) in healthy midlife women. Cross-sectional analyses were performed using data from 1,881 midlife women (average age 52.6 (±2.7) years) attending the 6(th) Annual follow-up visit of the multiethnic Study of Women's Health Across the Nation. T was weakly negatively associated with both HMW adiponectin and sOB-R (r= -0.12 and r= -0.10, respectively; P <0.001 for both), and positively associated with leptin (r=0.17; P <0.001). SHBG was more strongly and positively associated with both HMW adiponectin and sOB-R (r=0.29 and r=0.24, respectively; P <0.001 for both), and more strongly and negatively associated with leptin (r= -0.27; P <0.001). Adjustment for fat mass, insulin resistance or waist circumference only partially diminished associations with HMW adiponectin and sOB-R, but attenuated associations with leptin. In conclusion, in these midlife women, lower SHBG values, and to a lesser extent, higher T levels, were associated with lower, or less favorable, levels of adiponectin and sOB-R, independent of fat mass. These data suggest that variation in these adipose hormones resulting from lower SHBG levels, and possibly, though less likely, greater androgenicity, may contribute to susceptibility for metabolic and cardiovascular outcomes during midlife in women.

• Association of Osteocalcin With Obesity, Insulin Resistance, and Cardiovascular Risk Factors in Young Adults.

  Authors: Lynda E Polgreen, David R Jacobs, Brandon M Nathan, Julia Steinberger, Antoinette Moran, Alan R Sinaiko

  Obesity (Silver Spring, Md.).

  Low levels of osteocalcin (OCN), an osteoblast-specific hormone, have recently been associated with insulin resistance (homeostasis model assessment-insulin resistance (HOMA-IR)) and obesity,Low levels of osteocalcin (OCN), an osteoblast-specific hormone, have recently been associated with insulin resistance (homeostasis model assessment-insulin resistance (HOMA-IR)) and obesity, particularly in older adults. The aim of this study was to determine whether low levels of OCN would be associated with insulin resistance, obesity, and greater cardiovascular (CV) risk in young adults just emerging from adolescence. Undercarboxylated OCN and carboxylated OCN levels were measured on stored serum samples (total OCN = undercarboxylated OCN + carboxylated OCN) on 137 participants (67 males) at mean age 18.6 years (range 17-22 years). Insulin resistance was measured by hyperinsulinemic-euglycemic clamp (M(lbm)). Multivariable regression analyses with ln(OCN) as the independent variable were adjusted for age, sex, ethnicity, and BMI as indicated. Total OCN was inversely related to BMI, waist circumference, systolic blood pressure (SBP), interleukin (IL)-6, and directly related to M(lbm); only SBP remained significant (with M(lbm) P = 0.0560) after further adjustment for BMI. Carboxylated OCN was inversely related to BMI, waist circumference, SBP, low-density lipoprotein cholesterol (LDL-C), and directly related to adiponectin; SBP and adiponectin remained significant after further adjustment for BMI. There were no significant associations with undercarboxylated OCN. In summary, most associations with OCN were mediated via BMI. However, the significant associations of OCN with SBP, obesity, and adiponectin and borderline with M(lbm), suggest a potential role for OCN in the development of insulin resistance and CV risk that becomes more apparent with aging into older adulthood.

• Using Facebook and Text Messaging to Deliver a Weight Loss Program to College Students.

  Authors: Melissa A Napolitano, Sharon Hayes, Gary G Bennett, Allison Ives, Gary D Foster

  Obesity (Silver Spring, Md.).

  Between 31-35% of the college-aged population is overweight or obese, yet few weight loss trials for this population have been conducted. This study examined the feasibility, acceptability, andBetween 31-35% of the college-aged population is overweight or obese, yet few weight loss trials for this population have been conducted. This study examined the feasibility, acceptability, and initial efficacy of a technology-based 8 week weight loss intervention among college students. Students (N = 52) were randomly assigned to one of three arms: Facebook (n = 17); Facebook Plus text messaging and personalized feedback (n = 18); Waiting List Control (n = 17), with assessments at 4 weeks and 8 weeks (post-treatment). Participants were 20.47 + 2.19 years old, 86.45 + 17.11 kg, with a BMI of 31.36 + 5.3 kg/m(2). Participants were primarily female (86.5%), and the sample was racially diverse (57.7% Caucasian, 30.8% African American, 5.8% Hispanic, 5.7% other races). The primary outcome was weight loss after 8 weeks (post-treatment); 96.0% of the participants completed this assessment. At 8 weeks, the Facebook Plus group had significantly greater weight loss (-2.4 + 2.5 kg) than the Facebook (-0.63 + 2.4 kg) and Waiting List (-0.24+2.6 kg) (both Ps < 0.05). Weight change at 8 weeks was not significantly different between the Facebook and Waiting List groups. Results show preliminary efficacy and acceptability of the two active intervention arms (97.0% found the program helpful, 81.3% found the videos/handouts helpful, and 100% would recommend the program to others). Results indicate the potential for an innovative weight loss intervention that uses technology platforms (Facebook and text messaging) that are frequently used and already integrated into the cultural life of college students.

• The Effects of Overfeeding on Spontaneous Physical Activity in Obesity Prone and Obesity Resistant Humans.

  Authors: Stacy L Schmidt, Kristin A Harmon, Teresa A Sharp, Elizabeth H Kealey, Daniel H Bessesen

  Obesity (Silver Spring, Md.).

  Despite living in an environment that promotes weight gain in many individuals, some individuals maintain a thin phenotype while self-reporting expending little or no effort to control their weight.Despite living in an environment that promotes weight gain in many individuals, some individuals maintain a thin phenotype while self-reporting expending little or no effort to control their weight. When compared to obesity prone (OP) individuals, we wondered if obesity resistant (OR) individuals would have higher levels of spontaneous physical activity (SPA) or respond to short-term overfeeding by increasing their level of SPA in a manner that could potentially limit future weight gain. SPA was measured in fifty-five subjects (23 OP, 32 OR) using a novel physical activity monitoring system (PAMS) that measured body position and movement while subjects were awake for 6 days, either in a controlled eucaloric condition or during 3 days of overfeeding (1.4 x basal energy) and for the subsequent 3 days (ad libitum recovery period). Pedometers were also used before and during use of the PAMS to provide an independent measure of SPA. SPA was quantified by the PAMS as fraction of recording time spent lying, sitting or in an upright posture. Accelerometry, measured while subjects were in an upright posture, was used to categorize time spent in different levels of movement (standing, walking slowly, quickly, etc.). There were no differences in SPA between groups when examined across all study periods (p>0.05). However, 3 days following overfeeding, OP subjects significantly decreased the amount of time they spent walking (-2.0% of time, p=0.03), while OR subjects maintained their walking (+0.2%, p>0.05). The principle findings of this study are that increased levels of SPA either during eucaloric feeding or following short term overfeeding likely do not significantly contribute to obesity resistance while a decrease in SPA following overfeeding may contribute to future weight gain in individuals prone to obesity.

• BODY COMPOSITION AT 6 MONTHS OF LIFE:COMPARISON OF AIR-DISPLACEMENT PLETHYSMOGRAPHY AND DUAL ENERGY X-RAY ABSORPTIOMETRY.

  Authors: David A Fields, Ellen W Demerath, Angelo Pietrobelli, Paula C Chandler-Laney

  Obesity (Silver Spring, Md.).

  Body composition assessment during infancy is important because it is a critical period for obesity risk development, thus valid tools are needed to accurately, precisely, and quickly determine bothBody composition assessment during infancy is important because it is a critical period for obesity risk development, thus valid tools are needed to accurately, precisely, and quickly determine both fat and fat-free mass.The purpose of this study was to compare body composition estimates using dual-energy x-ray absorptiometry (DXA) and air displacement plethysmography (ADP) atsix-month old.We assessed the agreement between whole body composition using DXA and ADP in 84 full-term average-for-gestational-age boys and girls usingDXA (Lunar iDXAv11-30.062; Infant whole body analysis enCore 2007 software, GE, Fairfield, CT) and ADP (Infant Body Composition System v3.1.0, COSMED USA, Inc., Concord, CA). Although the correlations between DXA and ADP for %fat (r = 0.925), absolute fat mass (r = 0.969), and absolute fat-free mass (r = 0.945) were all significant, body composition estimates by DXA were greater for both %fat (31.1 ± 3.6% vs. 26.7± 4.7%; P< 0.001) and absolute fat mass (2,284± 449vs. 1,921± 492grams; P< 0.001), and lowerfor fat-free mass (5,022± 532 vs. 5,188± 508grams; P< 0.001) vs. ADP.Inter-method differences in %fatdecreased with increasingadiposity and differences in fat-free mass decreased with increasing infant age. Estimates of body composition determined by DXA and ADP at six- months of age were highly correlated, but did differ significantly. Additional work is required to identify the technical basis for these rather large inter-method differences in infant body composition.

• Sexual Functioning and Obesity: A Review.

  Authors: Ronette L Kolotkin, Christie Zunker, Truls Ostbye

  Obesity (Silver Spring, Md.).

  We review the literature on the relationship between obesity and sexual functioning. Eleven population-basedstudies, 20 cross-sectional non-population-based studies,and16weight loss studies areWe review the literature on the relationship between obesity and sexual functioning. Eleven population-basedstudies, 20 cross-sectional non-population-based studies,and16weight loss studies are reviewed.The consistency of findings suggests that the relationship between obesity and reduced sexual functioning is robust, despite diverse methods, instruments, and settings.In most population-based studies, erectile dysfunction (ED) is more common among obese men than among men of recommended weight. Studies of patients in clinical settings often include individuals with higher degrees of obesity, with most studies showing a relationship between obesity and lower levels of sexual functioning, especially ED. The few studies that include both gendersgenerally report more problems among women. Most studies of patients with comorbidities associated with obesity also find an association between obesity and reducedsexual functioning.Mostweight loss studies demonstrate improvement in sexual functioningconcurrent with weight reduction despite varying study designs, weight loss methods, and follow-up periods. We recommend that future studies (1) investigate differences and similarities between men and women with respect to obesity and sexual functioning, (2) use instruments that go beyond the assessment of sexual dysfunction to include additional concepts such as sexual satisfaction, interest, and arousal and, (3) assess how and the degree to which obese individuals are affected by sexual difficulties. Given the high prevalence of obesity and the inverse association between body mass and sexual functioning, we also recommend that sexual functioning should be more fully addressed by clinicians, both in general practice and in weight loss programs.

• Upregulation of plasma insulin-like growth factor binding protein 2 levelsafter biliopancreatic diversion in humans.

  Authors: Zhuo Li, Julie Martin, Paul Poirier, Sarah-Maude Caron-Cantin, Frédéric-Simon Hould, Simon Marceau, Picard Marceau, Frédéric Picard

  Obesity (Silver Spring, Md.).

  The biliopancreatic diversion surgery with duodenal switch (BPD-DS) is a surgical procedure that not only induces significant weight loss, but also promotes remission of diabetes. However, theThe biliopancreatic diversion surgery with duodenal switch (BPD-DS) is a surgical procedure that not only induces significant weight loss, but also promotes remission of diabetes. However, the mechanism responsible for this insulin-potentiating effect (both on sensitivity and production) is not yet clearly understood. The insulin-like growth factor (IGF) binding protein 2 (IGFBP-2) is a 36 kDa circulating protein that has been recently suggested to modulate insulin sensitization and fat accumulation. In humans, a low circulating concentration of IGFBP-2 has been associated with obesity and insulin resistance. We thus tested the hypothesis that BPD-DS would trigger an increase in IGFBP-2 levels. Plasma IGFBP-2 was quantified by ELISA in 77 severely obese men and women before and up to 1 year after BPD-DS surgery. Baseline IGFBP-2 levels were 159 ± 17 ng/mL. Plasma IGFBP-2 levels increased significantly as soon as 24 h after BPD-DS surgery and were further augmented at both 6 months and one year after the surgery, reaching 748 ± 65 ng/mL. Changes in IGFBP-2 concentrations were significantly and negatively associated with blood glucose, insulin, triglycerides, and total cholesterol levels. The present findings suggest that the rise in IGFBP-2 levels is associated with the improvements in glucose and lipid metabolism in the short and long term after BPD-DS. The mechanisms for the augmentation in IGFBP-2 after BPD-DS and its contribution to insulin sensitization remain to be elucidated.

• Short-term Lenalidomide (Revlimid) Administration Ameliorates Cardiomyocyte Contractile Dysfunction in ob/ob Obese Mice.

  Authors: Linlin Li, Yinan Hua, Maolong Dong, Quan Li, Derek T Smith, Ming Yuan, Kyla R Jones, Jun Ren

  Obesity (Silver Spring, Md.).

  Lenalidomide is a potent immunomodulatory agent capable of downregulating proinflammatory cytokines such as TNF-α and up-regulating anti-inflammatory cytokines. Lenalidomide has been shown to elicitLenalidomide is a potent immunomodulatory agent capable of downregulating proinflammatory cytokines such as TNF-α and up-regulating anti-inflammatory cytokines. Lenalidomide has been shown to elicit cardiovascular effects although its impact on cardiac function remains obscure. This study was designed to examine the effect of lenalidomide on cardiac contractile function in ob/ob obese mice. C57BL lean and ob/ob obese mice were given lenalidomide (50 mg/kg/d, p.o.) for 3 days. Body fat composition was assessed by dual energy X-ray absorptiometry. Cardiomyocyte contractile and intracellular Ca(2+) properties were evaluated. Expression of TNF-α, IL-6, Fas, Fas ligand (FasL), the short-chain fatty acid receptor GPR41, the NFКB regulator IКB, ER stress, the apoptotic protein markers Bax, Bcl-2, Caspase-8, tBid, cytosolic cytochrome C and Caspase-12, and the stress signaling molecules p38 and ERK were evaluated by western blot. ob/ob mice displayed elevated serum TNF-α and IL-6 levels, fat composition and glucose intolerance, the effects of which except glucose intolerance and fat composition were attenuated by lenalidomide. Cardiomyocytes from ob/ob mice exhibited depressed peak shortening and maximal velocity of shortening/relengthening, prolonged time-to-peak shortening and time-to-90% relengthening as well as intracellular Ca(2+) mishandling, which were ablated by lenalidomide. Western blot analysis revealed elevated levels of TNF-α, IL-6, Fas, Bip, Bax, Caspase-8, tBid, cleaved Caspase-3 Caspase-12, cytochrome C, phosphorylation of p38 and ERK in ob/ob mouse hearts, the effects of which with the exception of Bip, Bax and Caspase-12 were alleviated by lenalidomide. Taken together, these data suggest that lenalidomide is protective against obesity-induced cardiomyopathy possibly through antagonism of cytokine/Fas-induced activation of stress signaling and apoptosis.

• Adherence to Behavioral Targets and Treatment Attendance during a Pediatric Weight Control Trial(¥).

  Authors: Kelly R Theim, Meghan M Sinton, Andrea B Goldschmidt, Dorothy J Van Buren, Angela Celio Doyle, Brian E Saelens, Richard I Stein, Leonard H Epstein, Denise E Wilfley

  Obesity (Silver Spring, Md.).

  Better weight loss outcomes are achieved in adults and youth who adhere to obesity treatment regimens (i.e., session attendance and prescribed changes in weight control behaviors). However, moreBetter weight loss outcomes are achieved in adults and youth who adhere to obesity treatment regimens (i.e., session attendance and prescribed changes in weight control behaviors). However, more research is needed regarding children's adherence to a range of behaviors relevant for weight maintenance over long-term follow-up. Overweight children (N=101, aged 7-12 years), along with an overweight parent, participated in a 20-week family-based behavioral weight loss treatment (FBT) and were then assigned to either a behaviorally-focused or socially-focused 16-week weight maintenance treatment (MT). Treatment attendance and child and parent adherence (i.e., reported use of skills targeted within treatment) were examined in relation to child percent overweight change from baseline to post-FBT, post-MT, and 2-year follow-up. Higher attendance predicted better child weight outcomes at post-MT, but not at 2-year follow-up. Adherence to self-regulatory skills/goal-setting skills predicted child weight outcomes at 2-year follow-up among the behaviorally-focused MT group. Future research is needed to examine mediators of change within family-based weight control interventions, including behavioral and socially-based targets. Incorporating self-regulatory weight maintenance skills into a comprehensive MT may maximize children's sustained weight control.

• Bright Start: Description and main outcomes from a group-randomized obesity prevention trial in American Indian children.

  Authors: Mary Story, Peter J Hannan, Jayne A Fulkerson, Bonnie Holy Rock, Mary Smyth, Chrisa Arcan, John H Himes

  Obesity (Silver Spring, Md.).

  The aim of the Bright Start study was to develop and test the effectiveness of a school environment intervention, supplemented with family involvement, to reduce excessive weight gain by increasingThe aim of the Bright Start study was to develop and test the effectiveness of a school environment intervention, supplemented with family involvement, to reduce excessive weight gain by increasing physical activity and healthy eating practices among kindergarten and first grade American Indian children. Bright Start was a group-randomized, school-based trial involving 454 children attending 14 schools on the Pine Ridge Reservation in South Dakota. Children were followed from the beginning of their kindergarten year through the end of first grade. Main outcome variables were mean BMI, mean percent body fat, and prevalence of overweight/obese children. The goals of the intervention were to: increase physical activity at school to at least 60 min/day; modify school meals and snacks; and involve families in making behavioral and environmental changes at home. At baseline, 32% of boys and 25% of girls were overweight/obese. While the intervention was not associated with statistically significant change in mean levels of BMI, BMI-Z, skinfolds or percentage body fat, the intervention was associated with a statistically significant net decrease of 10% in the prevalence of overweight. Intervention children experienced a 13.4% incidence of overweight, while the control children experienced a corresponding incidence of 24.8%; a difference of -11.4% (p=0.033). The intervention significantly reduced parent reported mean child intakes of sugar-sweetened beverages, whole milk and chocolate milk. Changes in duration of school physical activity were not significant. Because obesity is the most daunting health challenge facing American Indian children today, more intervention research is needed to identify effective approaches.

• Ski overexpression in skeletal muscle modulates genetic programs that control susceptibility to diet-induced obesity and insulin signaling.

  Authors: Marianne Diaz, Nick Martel, Rebecca L Fitzsimmons, Natalie A Eriksson, Gary Cowin, Gethin Thomas, Kim-Anh Lê Cao, George E O Muscat, Gary M Leong

  Obesity (Silver Spring, Md.).

  Transgenic (Tg) mice overexpressing chicken Ski (c-Ski) have marked decrease in adipose mass with skeletal muscle hypertrophy. Recent evidence indicates a role for c-Ski in lipogenesis and energyTransgenic (Tg) mice overexpressing chicken Ski (c-Ski) have marked decrease in adipose mass with skeletal muscle hypertrophy. Recent evidence indicates a role for c-Ski in lipogenesis and energy expenditure. In the present study wild type (WT) and c-Ski mice were challenged on a high fat (HF) diet to determine if c-Ski mice were resistant to diet-induced obesity. During the HF feeding WT mice gained significantly more weight than chow-fed animals, whilst c-Ski mice were partially resistant to the effects of the HF diet on weight. Body composition analysis confirmed the decreased adipose mass in c-Ski mice compared to WT mice. c-Ski mice possess a similar metabolic rate and level of food consumption to WT littermates, despite lower activity levels and on chow diet show mild glucose intolerance relative to WT littermates. On HF diet, glucose tolerance surprisingly remained unchanged in c-Ski mice, while it worsened in WT mice. Skeletal muscle of c-Ski mice exhibit impaired insulin-stimulated Akt phosphorylation and glucose uptake. In concordance, gene expression profiling of skeletal muscle of chow and HF-fed mice indicated that Ski suppresses gene expression associated with insulin signaling and glucose uptake and alters gene pathways involved in myogenesis and adipogenesis. In conclusion, c-Ski mice are partially resistant to diet-induced obesity and display aberrant insulin signaling and glucose homeostasis which is associated with alterations in gene expression that inhibit lipogenesis and insulin signaling. These results suggest Ski plays a major role in skeletal muscle metabolism and adipogenesis and hence influences risk of obesity and diabetes.

• Predictors of Attendance in a Practical Clinical Trial of TwoPediatric Weight Management Interventions.

  Authors: Cd Jensen, Bs Aylward, Rg Steele

  Obesity (Silver Spring, Md.).

  The objective of this study was to evaluate demographic and psychosocial predictors of attendance in a family-based behavioral weight management clinical trial. Ninety-three children and adolescentsThe objective of this study was to evaluate demographic and psychosocial predictors of attendance in a family-based behavioral weight management clinical trial. Ninety-three children and adolescents ages 7-17 (M age = 11.59, SD = 2.6) who were either overweight or obese (M BMI percentile = 98.2) and their parents received either a ten-session behavioral treatment or a three-session brief family intervention in the context of a randomized clinical trial.(10) Psychosocial and anthropometric measures were obtained prior to enrollment and at the end of ten weeks for both treatment groups. Univariate linear regression and hierarchical multiple regression analyses were used to identify predictors of attendance to treatment from an a priori set of hypothesized predictors. Three variables demonstrated significant associations with the dependent variable, percent of treatment sessions attended. Specifically, distance from participant's home to treatment site, lower gross family income, and youth self-report of depressive symptoms were each associated with lower percent attendance (all ps<.05) These results corroborate (i.e., income, depressive symptoms) and expand (i.e., distance from treatment site) previous reports in the literature of potential barriers to effective treatment for pediatric obesity, and suggest the need for research on treatment delivery methods that could increase participation among low-income families (e.g., eHealth, mHealth options). Depressive symptoms could represent an additional barrier to treatment attendance, suggesting that assessment and treatment for these symptoms may be appropriate prior to commencing weight management treatment.

• Diet composition and activity level of at risk and metabolically healthy obese American adults.

  Authors: Arlene L Hankinson, Martha L Daviglus, Linda Van Horn, Queenie Chan, Ian Brown, Elaine Holmes, Paul Elliott, Jeremiah Stamler

  Obesity (Silver Spring, Md.).

  Obesity often clusters with other major cardiovascular disease risk factors, yet a subset of the obese appears to be protected from these risks. Two obesity phenotypes are described, 1)Obesity often clusters with other major cardiovascular disease risk factors, yet a subset of the obese appears to be protected from these risks. Two obesity phenotypes are described, 1) "metabolically healthy" obese, broadly defined as body mass index (BMI) ≥ 30 kg/m(2) and favorable levels of blood pressure, lipids, and glucose; and 2) "at risk" obese, BMI ≥ 30 with unfavorable levels of these risk factors. More than 30% of obese American adults are metabolically healthy. Diet and activity determinants of obesity phenotypes are unclear. We hypothesized that metabolically healthy obese have more favorable behavioral factors, including less adverse diet composition and higher activity levels than at risk obese in the multi-ethnic group of 775 obese American adults ages 40-59 years from the International Population Study on Macro/Micronutrients and Blood Pressure (INTERMAP) cohort. In gender stratified analyses, mean values for diet composition and activity behavior variables, adjusted for age, race, and education, were compared between metabolically healthy and at risk obese. Nearly 1 in 5 (149/775, or 19%) of obese American INTERMAP participants were classified as metabolically healthy obese. Diet composition and most activity behaviors were similar between obesity phenotypes, although metabolically healthy obese women reported higher sleep duration than at risk obese women. These results do not support hypotheses that diet composition and/or physical activity account for the absence of cardiometabolic abnormalities in metabolically healthy obese.

• Allergen-induced Bone Marrow Eosinophilopoiesis and Airways Eosinophilic Inflammation in Leptin-deficient ob/ob Mice.

  Authors: Leticia Lintomen, Marina Ciarallo Calixto, André Schenka, Edson Antunes

  Obesity (Silver Spring, Md.).

  Asthma and obesity are growing epidemics in the world. It is well-established that obesity worsens the asthma outcomes. High-fat diet-induced obesity in mice exacerbates the pulmonary eosinophilicAsthma and obesity are growing epidemics in the world. It is well-established that obesity worsens the asthma outcomes. High-fat diet-induced obesity in mice exacerbates the pulmonary eosinophilic inflammation. We have used wild type (WT) and ob/ob mice to further explore the mechanisms by which obesity aggravates the pulmonary eosinophilic inflammation. The eosinophil (EO) number in BAL fluid, lung tissue, blood and bone marrow were evaluated at 24, 48 and 72 h after ovalbumin (OVA) challenge in sensitized mice. The basal EO number (PBS-instilled mice) in lung tissue was about of 3.5-fold greater in ob/ob compared with WT mice. OVA challenge in ob/ob mice promoted an EO accumulation into the lung that was accompanied by a lower emigration to airways lumen (BAL fluid) in comparison with WT mice. OVA challenge also markedly elevated the number of mature and immature EO in bone marrow of ob/ob mice at 24 h compared with WT group. Blood EO at 48 h was markedly greater in ob/ob mice. TNF-α and IL-10 levels in BAL fluid were significantly higher in ob/ob mice, whereas no changes for IL-5 and eotaxin were found. The IL-6 levels were significantly lower in ob/ob mice. In conclusion, OVA challenge in ob/ob obese mice potentiates eosinophilopoiesis and promotes an accumulation of EO into the lung tissue, delaying their transit to airways lumen. The longer EO remain into the lung tissue is likely to contribute, at least in part, to the asthma worsened by obesity.

• Effects of sleep restriction on glucose control and insulin secretion during diet-induced weight loss.

  Authors: A V Nedeltcheva, J G Imperial, P D Penev

  Obesity (Silver Spring, Md.).

  Insufficient sleep is associated with changes in glucose tolerance, insulin secretion, and insulin action. Despite widespread use of weight-loss diets for metabolic risk reduction, the effects ofInsufficient sleep is associated with changes in glucose tolerance, insulin secretion, and insulin action. Despite widespread use of weight-loss diets for metabolic risk reduction, the effects of insufficient sleep on glucose regulation in overweight dieters are not known. To examine the consequences of recurrent sleep restriction on 24-hour blood glucose control during diet-induced weight loss, 10 overweight and obese adults (3F/7M; mean [SD] age 41 [5] y; BMI 27.4 [2.0] kg/m(2)) completed two 14-day treatments with hypocaloric diet and 8.5 or 5.5-h nighttime sleep opportunity in random order 7 [3] months apart. Oral and intravenous glucose tolerance test (IVGTT) data, fasting lipids and free-fatty acids (FFA), and 24-hour blood glucose, insulin, C-peptide, and counter-regulatory hormone measurements were collected after each treatment. Participants had comparable weight loss (1.0 [0.3] BMI units) during each treatment. Bedtime restriction reduced sleep by 131 [30] min/day. Recurrent sleep curtailment decreased 24-hour serum insulin concentrations (i.e. enhanced 24-hour insulin economy) without changes in oral glucose tolerance and 24-hour glucose control. This was accompanied by a decline in fasting blood glucose, increased fasting FFA which suppressed normally following glucose ingestion, and lower total and LDL cholesterol concentrations. Sleep-loss-related changes in counter-regulatory hormone secretion during the IVGTT limited the utility of the test in this study. In conclusion, sleep restriction enhanced 24-hour insulin economy without compromising glucose homeostasis in overweight individuals placed on a balanced hypocaloric diet. The changes in fasting blood glucose, insulin, lipid and FFA concentrations in sleep-restricted dieters resembled the pattern of human metabolic adaptation to reduced carbohydrate availability.

• Sympathetic denervation of one white fat depot changes norepinephrine content and turnover in intact white and brown fat depots.

  Authors: Ruth B S Harris

  Obesity (Silver Spring, Md.).

  It is well established that the sympathetic nervous system regulates adipocyte metabolism and recently it has been reported that sensory afferents from white fat overlap anatomically with sympatheticIt is well established that the sympathetic nervous system regulates adipocyte metabolism and recently it has been reported that sensory afferents from white fat overlap anatomically with sympathetic efferents to white fat. The studies described here characterize the response of intact fat pads to selective sympathectomy (local 6-hydroxydopamine injections) of inguinal (ING) or epididymal (EPI) fat in male NIH Swiss mice and provide in vivo evidence for communication between individual white and brown fat depots. The contralateral ING pad, both EPI pads, perirenal and mesenteric pads were significantly enlarged four weeks after denervating one ING pad, but only intrascapular brown fat (IBAT) increased when both ING pads were denervated. Denervation of one or both EPI pad had no effect on fat depot weights. In an additional experiment, NE turnover was inhibited in ING, retroperitoneal, mesenteric and IBAT two days after denervation of both EPI or of both ING pads. NE content was reduced to 10-30% of control values in all fat depots. There was no relation between early changes in NE turnover and fat pad weight 4 weeks after denervation, even though the reduction in NE content of intact fat pads was maintained. These data demonstrate that there is communication among individual fat pads, presumably through central integration of activity of sensory afferent and sympathetic efferent fibers,that changes sympathetic drive to white adipose tissue in a unified manner. In specific situations, removal of sympathetic efferents to one pad induces a compensatory enlargement of other intact depots.

• Neighborhood health-promoting resources and obesity risk (the Multi-Ethnic Study of Atherosclerosis).

  Authors: Amy H Auchincloss, Mahasin S Mujahid, Mingwu Shen, Erin D Michos, Melicia C Whitt-Glover, Ana V Diez Roux

  Obesity (Silver Spring, Md.).

  While behavioral change is necessary to reverse the obesity epidemic, it can be difficult to achieve and sustain in unsupportive residential environments. This study hypothesized that environmentalWhile behavioral change is necessary to reverse the obesity epidemic, it can be difficult to achieve and sustain in unsupportive residential environments. This study hypothesized that environmental resources supporting walking and a healthy diet are associated with reduced obesity incidence. Data came from 4008 adults aged 45-84 at baseline who participated in a neighborhood ancillary study of the Multi-Ethnic Study of Atherosclerosis. Participants were enrolled at 6 study sites at baseline (2000-2002) and neighborhood scales were derived from a supplementary survey that asked community residents to rate availability of healthy foods and walking environments for a one-mile buffer area. Obesity was defined as body mass index (BMI) >=30 kg/m(2). Associations between incident obesity and neighborhood exposure were examined using proportional hazards and generalized linear regression. Among 4008 non-obese participants, 406 new obesity cases occurred during 5 years of follow-up. Neighborhood healthy food environment was associated with 10% lower obesity incidence per standard deviation increase neighborhood score. The association persisted after adjustment for baseline BMI and individual level covariates (HR 0.88, 95% CI: 0.79, 0.97), and for correlated features of the walking environment but confidence intervals widened to include the null (HR 0.89, 95% CI: 0.77, 1.03). Associations between neighborhood walking environment and lower obesity were weaker and did not persist after adjustment for correlated neighborhood healthy eating amenities (HR 0.98, 95% CI 0.84, 1.15). Altering the residential environment so that healthier behaviors and lifestyles can be easily chosen may be a pre-condition for sustaining existing healthy behaviors and for adopting new healthy behaviors.

• Overweight in adolescence is related to increased risk of future urothelial cancer.

  Authors: Adi Leiba, Jeremy D Kark, Arnon Afek, Zohar Levi, Micha Barchana, Dorit Tzur, Estela Derazne, Asaf Vivante, Ari Shamiss

  Obesity (Silver Spring, Md.).

  Obesity has been linked to various malignancies, but a clear relation of overweight with urothelial cancer has not been established. We assessed the association between adolescent obesity and futureObesity has been linked to various malignancies, but a clear relation of overweight with urothelial cancer has not been established. We assessed the association between adolescent obesity and future risk for urothelial cancer. Medical data on 1,110,835 Israeli adolescents examined for fitness for military duty between 1967 and 2005 were linked to the National Cancer Registry in this nationwide population-based cohort study. We used Cox proportional hazards modeling to estimate the covariate-adjusted hazard ratio (HR) for urothelial cancer associated with body-mass index (BMI) measured at age 17. The mean follow up of 17.6±10.8 years reflected 19,576,635 person years, during which 661 examinees developed urothelial cancer of the bladder, ureter or renal pelvis. BMI ≥ 85th standard percentile in adolescence significantly predicted increased risk of urothelial cancer with a HR (adjusted for year of birth, education and religiosity) of 1.42 (95% confidence interval (CI), 1.13 to 1.77, p=0.002). Similar results were observed using the ≥25 kg/m(2) definition of overweight [HR = 1.36 (95% CI, 1.08 to 1.72), p=0.008]. Incidence of urothelial cancer was significantly lower in the more educated and among those who attended religious schools.Overweight in adolescence is related to increased risk of future urothelial cancer. In view of the growing incidence of both urothelial cancer and adolescent obesity, our study suggests an avenue for possible prevention of urothelial cancer.

• Placental Weight Mediates the Effects of Prenatal Factors on Fetal Growth: the Extent Differs by Preterm Status.

  Authors: Fengxiu Ouyang, Margaret Parker, Sandra Cerda, Colleen Pearson, Lingling Fu, Matthew W Gillman, Barry Zuckerman, Xiaobin Wang

  Obesity (Silver Spring, Md.).

  Elevated pre-pregnancy body mass index (BMI), excessive gestational weight gain (GWG), and gestational diabetes (GDM) are known determinants of fetal growth. The role of placental weight is unclear.Elevated pre-pregnancy body mass index (BMI), excessive gestational weight gain (GWG), and gestational diabetes (GDM) are known determinants of fetal growth. The role of placental weight is unclear. We aimed to examine the extent to which placental weight mediates the associations of pre-pregnancy BMI, GWG, and GDM with birthweight-for-gestational age, and whether the relationships differ by preterm status. We examined 1035 mother-infant pairs at birth from the Boston Birth Cohort. Data were collected by questionnaire and clinical measures. Placentas were weighed without membranes or umbilical cords. We performed sequential models excluding and including placental weight, stratified by preterm status. We found that 21% of mothers were obese, 42% had excessive GWG, and 5% had GDM. 41% were preterm. Among term births, after adjustment for sex, gestational age, maternal age, race, parity, education, smoking and stress during pregnancy, birthweight-for-gestational age z-score was 0.55 (0.30, 0.80) units higher for pre-pregnancy obesity vs. normal weight. It was 0.34 (0.13, 0.55) higher for excessive vs. adequate GWG, 0.67 (0.24, 1.10) for GDM vs. no DM, with additional adjustment for pre-pregnancy BMI. Adding placental weight to the models attenuated the estimates for pre-pregnancy obesity by 20%, excessive GWG by 32%, and GDM by 21%. Among preterm infants, GDM was associated with 0.67 (0.34, 1.00) higher birthweight-for-gestational age z-score, but pre-pregnancy obesity and excessive GWG were not. Attenuation by placental weight was 36% for GDM. These results suggest that placental weight partially mediates the effects of pre-pregnancy obesity, GDM and excessive GWG on fetal growth among term infants.

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