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1.  Role of Skeletal Muscle Mitochondrial Density on Exercise-Stimulated Lipid Oxidation 
Obesity (Silver Spring, Md.)  2011;20(7):1387-1393.
Reduced skeletal muscle mitochondrial density is proposed to lead to impaired muscle lipid oxidation and increased lipid accumulation in sedentary individuals. We assessed exercise-stimulated lipid oxidation by imposing a prolonged moderate-intensity exercise in men with variable skeletal muscle mitochondrial density as measured by citrate synthase (CS) activity. After a 2-day isoenergetic high-fat diet, lipid oxidation was measured before and during exercise (650 kcal at 50% VO2 max) in 20 healthy men with either high (HI-CS = 24 ± 1; mean ± s.e.) or low (LO-CS = 17 ± 1 nmol/min/mg protein) muscle CS activity. Vastus lateralis muscle biopsies were obtained before and immediately after exercise. Respiratory exchange data and blood samples were collected at rest and throughout the exercise. HI-CS subjects had higher VO2 max (50 ± 1 vs. 44 ± 2 ml/kg fat free mass/min; P = 0.01), lower fasting respiratory quotient (RQ) (0.81 ± 0.01 vs. 0.85 ± 0.01; P = 0.04) and higher ex vivo muscle palmitate oxidation (866 ± 168 vs. 482 ± 78 nmol/h/mg muscle; P = 0.05) compared to LO-CS individuals. However, whole-body exercise-stimulated lipid oxidation (20 ± 2 g vs. 19 ± 1 g; P = 0.65) and plasma glucose, lactate, insulin, and catecholamine responses were similar between the two groups. In conclusion, in response to the same energy demand during a moderate prolonged exercise bout, reliance on lipid oxidation was similar in individuals with high and low skeletal muscle mitochondrial density. This data suggests that decreased muscle mitochondrial density may not necessarily impair reliance on lipid oxidation over the course of the day since it was normal under a high-lipid oxidative demand condition. Twenty-four-hour lipid oxidation and its relationship with mitochondrial density need to be assessed.
PMCID: PMC4104481  PMID: 21681225
2.  Validity of weight loss to estimate improvement in body composition in individuals attending a wellness center 
Obesity (Silver Spring, Md.)  2011;19(11):2274-2279.
The accuracy of weight loss in estimating successful changes in body composition (BC), namely fat mass loss, is not known and was addressed in our study.
To assess the correlation between change in body weight and change in fat mass (FM), fat % and fat-free mass (FFM), 465 participants (41% male; 41±13years), who met the criteria for weight change at a wellness center, underwent air-displacement plethysmography. Body weight and BC were measured at the same time. We categorized the change in body weight, FM and FFM as an increase if there was >1 kg gain, a decrease if there was >1 kg loss and no change if the difference was ≤ 1 kg. We estimated the diagnostic performance of weight change to identify improvement in BC. After a median time of 132 days, 255 people who lost >1 kg of weight, 216(84.7%) had lost >1 kg of FM, but 69(27.1%) had lost >1 kg of FFM. Of the 143 people with no weight change, 42(29.4%) had actually lost >1kg of FM. Of the 67 who gained >1 kg of weight at follow-up, in 23(34.3%) this was due to an increase in FFM but not in FM. Weight change had a NPV of 73%. Mean weight change was 2.4 kg.
Our results indicate that favorable improvements in BC may go undetected in almost 1/3 of people whose weight remains the same and in 1/3 of people who gain weight after attending a wellness center. These results underscore the potential role of BC measurements in people attempting lifestyle changes.
PMCID: PMC4103167  PMID: 21566566
3.  Gestational Weight Gain and Neonatal Adiposity in the Hyperglycemia and Adverse Pregnancy Outcome Study-North American Region 
Obesity (Silver Spring, Md.)  2014;22(7):1731-1738.
To examine the associations between gestational weight gain (GWG) exceeding Institute of Medicine (IOM) guidelines and neonatal adiposity in the five North American field centers of the Hyperglycemia and Adverse Pregnancy Outcome study.
GWG was categorized as less than, within, or greater than 2009 IOM guidelines. Birthweight, body fat percentage, cord serum C-peptide, and sum of neonatal flank, subscapular, and triceps skin fold thicknesses were dichotomized as >90th percentile or ≤90th percentile obtained by quantile regression. Logistic regression analysis was used.
Of the 5297 participants, 11.6% gained less, 31.9% gained within, and 56.5% gained more than the recommendation. With adjustment for glucose tolerance levels, normal and overweight women who gained more than the recommendation had increased odds of delivering infants with sum of skin folds >90th percentile (OR =1.75 and 4.77, respectively) and percentage body fat >90th percentile (OR =2.41 and 2.59, respectively), and normal weight and obese women who gained more than the recommendation had increased odds of delivering infants with birthweight >90th percentile (OR =2.80 and 1.93, respectively) compared to women who gained within the recommendation.
This analysis showed independent associations between exceeding IOM GWG recommendations and neonatal adiposity in normal and overweight women, controlling for glucose tolerance levels.
PMCID: PMC4100536  PMID: 24634400
4.  The association of pericardial fat with calcified coronary plaque 
Obesity (Silver Spring, Md.)  2008;16(8):1914-1919.
Pericardial fat has a higher secretion of inflammatory cytokines than subcutaneous fat. Cytokines released from pericardial fat around coronary arteries may act locally on the adjacent cells.
We examined the relationship between pericardial fat and calcified coronary plaque.
Participants in the community-based Multi-Ethnic Study of Atherosclerosis underwent a computed tomography scan for the assessment of calcified coronary plaque in 2001/02. We measured the volume of pericardial fat using these scans in 159 whites and blacks without symptomatic coronary heart disease from Forsyth County, NC, aged 55–74 years.
Calcified coronary plaque was observed in 91 participants (57%). After adjusting for height, a one standard deviation increment in pericardial fat was associated with an increased odds of calcified coronary plaque (odds ratio (95% confidence interval): 1.92 (1.27, 2.90)). With further adjustment of other cardiovascular factors, pericardial fat was still significantly associated with calcified coronary plaque. This relationship did not differ by gender and ethnicity. On the other hand, body mass index and height-adjusted waist circumference were not associated with calcified coronary plaque.
Pericardial fat is independently associated with calcified coronary plaque.
PMCID: PMC4098129  PMID: 18535554
coronary heart disease; body mass index; waist circumference
5.  Ascent to Altitude as a Weight Loss Method: The Good and Bad of Hypoxia Inducible Factor Activation 
Obesity (Silver Spring, Md.)  2013;22(2):311-317.
Given the epidemic of obesity worldwide there is a need for more novel and effective weight loss methods. Altitude is well known to be associated with weight loss and has actually been used as a method of weight reduction in obese subjects. This review demonstrates the critical role of hypoxia inducible factor (HIF) in bringing about the reduction in appetite and increase in energy expenditure characteristic of hypobaric hypoxia
Design and methods
A MEDLINE search of English language articles through February 2013 identified publications associating altitude or hypobaric hypoxia with key words to include hypoxia inducible factor, weight loss, appetite, basal metabolic rate, leptin, cellular energetics, and obesity. The data from these articles were synthesized to formulate a unique and novel mechanism by which HIF activation leads to alterations in appetite, basal metabolic rate, and reductions in body adiposity.
A synthesis of previously published literature revealed mechanisms by which altitude induces activation of HIF, thereby suggesting this transcription factor regulates changes in cellular metabolism/energetics, activation of the central nervous system, as well as peripheral pathways leading to reductions in food intake and increases in energy expenditure.
Here we present a unifying hypothesis suggesting that activation of HIF under conditions of altitude potentially leads to metabolic benefits that are dose dependent, gender and genetic specific, and results in adverse effects if the exposure is extreme.
PMCID: PMC4091035  PMID: 23625659
6.  Relation of Misperception of Healthy Weight to Obesity in Urban Black Men 
Obesity (Silver Spring, Md.)  2009;18(7):1318-1322.
This study examined the relation between misperception of healthy weight and obesity, as well as moderators of this relation, in a sample of middle-aged black men. Survey data from 404 mostly immigrant, black males living in greater New York City were collected as part of a larger randomized controlled trial. Data included measures of health status, BMI, perceived healthy weight, and misperception of healthy weight. Misperception of healthy weight was more frequent among obese men (90.2%) than nonobese men (48.7%) (P < 0.001). Mean level of misperception was also significantly higher in obese men than nonobese men (P < 0.001). Health status moderated the relation between misperception of healthy weight and obesity: obese men who felt healthy or who had fewer comorbid conditions had greater misperception of healthy weight than obese men who felt unhealthy or had relatively more comorbid conditions (P < 0.01). Our findings demonstrate that misperception of healthy weight discriminates between obese and nonobese black men, and the magnitude of this relation is exacerbated in obese men who are relatively healthy. Future studies should determine the prevalence of misperception of healthy weight in more diverse populations and identify potential mediators of the relation between misperception of healthy weight and obesity.
PMCID: PMC4089869  PMID: 19876006
7.  Racial Differences in Nonalcoholic Fatty Liver Disease in the U.S. Population 
Obesity (Silver Spring, Md.)  2013;22(1):292-299.
To characterize the prevalence of Non-Alcoholic Fatty Liver Disease (NAFLD) by race in a nationally representative sample of the U.S. population and to investigate potential explanatory factors for racial disparities.
Cross-sectional study of 4,037 non-Hispanic white, 2,746 non-Hispanic black, and 2,892 Mexican-American adults in the Third National Health and Nutrition Examination Survey. NAFLD was defined using ultrasound and with elevated aminotransferases.
Age-adjusted prevalence of NAFLD was highest in Mexican-Americans (21.2%), followed by non-Hispanic whites (12.5%), and was lowest in non-Hispanic blacks (11.6%). Even after adjustment for demographic, lifestyle, adiposity, and metabolic factors, compared to non-Hispanic whites, Mexican-Americans were more likely to have NAFLD (OR: 1.67, 95% CI: 1.26, 2.22). Non-Hispanic blacks were significantly less likely to have NAFLD with elevated aminotransferases (OR: 0.51, 95% CI: 0.27, 0.97). Racial differences were attenuated among those with normal body mass index and/or among “never drinkers.”
In this representative sample of the U.S. population, we found significant racial differences in the prevalence of ultrasound-defined NAFLD (with and without elevated liver enzymes). The racial differences were not fully explained by lifestyle, adiposity and metabolic factors. More works is needed to identify potential contributors.
PMCID: PMC3690150  PMID: 23512725
Liver; Race; Ethnicity; Obesity; NHANES III
8.  Fat Accumulation in the Liver of Obese Rats is Alleviated by Soy Protein Isolate through β-catenin signaling 
Obesity (Silver Spring, Md.)  2013;22(1):151-158.
The current study aim to investigate the effects of SPI on Wnt/β-catenin signaling in the liver of obese rats, as well as the roles of this pathway in regulating the hepatic fat accumulation.
Design and Methods
Obese and lean Zucker rats were fed diets containing either casein or SPI as protein source for 17 weeks. Histology and biochemical analysis, real-time PCR, Western blot, immunostaining, short interfering RNA assay were performed for liver samples.
Our study showed that fat content was significantly lowered in the liver of SPI-fed obese rats, accompanied by a reduction in hepatocellular vacuolation, compared to the casein-fed control. β-catenin protein level in the liver of obese rats was down-regulated compared to the lean group, indicating that the obese genotype exhibits an overall reduction in Wnt signaling. Importantly the repression of β-catenin in the obese rats was alleviated by feeding the SPI diet. siRNA treatment in rat hepatoma cells confirmed that silencing of β-catenin exacerbated fatty acid-induced fat accumulation, which implicated an important function of Wnt/β-catenin signaling in hepaticfat metabolism.
SPI intake restored β-catenin signaling and alleviated hepatic fat accumulation and liver damage in the obese rats.
PMCID: PMC3690171  PMID: 23512909
diet; hepatic fat; β-catenin signaling; SPI; obese Zucker rat
9.  Body mass index and mortality among blacks and whites in the Prostate, Lung, Colorectal and Ovarian (PLCO) Cancer Screening Trial 
Obesity (Silver Spring, Md.)  2013;22(1):260-268.
In a large prospective cohort, we examined the relationship of BMI with mortality among blacks and compared the results to those among whites in this population.
Design and methods
The study population consisted of 7,446 non-Hispanic black and 130,598 white participants, ages 49–78 at enrollment, in the Prostate, Lung, Colorectal and Ovarian (PLCO) Cancer Screening Trial. BMI at baseline, BMI at age 20, and BMI change were calculated using self-reported and recalled height and weight. Relative risks were stratified by race and sex and adjusted for age, education, marital status, and smoking.
1,495 black and 18,236 white participants died during follow-up (mean=13 years). Clear J-shaped associations between BMI and mortality were observed among white men and women. Among black men and women, the bottoms of these curves were flatter, and increasing risks of death with greater BMI were observed only at higher BMI levels (≥35.0). Associations for BMI at age 20 and BMI change also appeared to be stronger in magnitude in whites versus blacks, and these racial differences appeared to be more pronounced among women.
Our results suggest that BMI may be more weakly associated with mortality in blacks, particularly black women, than in whites.
PMCID: PMC3690173  PMID: 23512729
10.  Doctor shopping by overweight and obese patients is associated with increased healthcare utilization 
Obesity (Silver Spring, Md.)  2013;21(7):1328-1334.
Negative interactions with healthcare providers may lead patients to switch physicians or “doctor shop.” We hypothesized that overweight and obese patients would be more likely to doctor shop, and as a result, have increased rates of emergency department (ED) visits and hospitalizations as compared to normal weight non-shoppers. We combined claims data from a health plan in one state with information from beneficiaries’ health risk assessments. The primary outcome was “doctor shopping,” which we defined as having outpatient claims with ≥5 different primary care physicians (PCPs) during a 24-month period. The independent variable was standard NIH categories of weight by BMI. We performed multivariate logistic regression to evaluate the association between weight categories and doctor shopping. We conducted multivariate zero-inflated negative binominal regression to evaluate the association between weight-doctor shopping categories with counts of ED visits and hospitalizations. Of the 20,726 beneficiaries, the mean BMI was 26.3 kg/m2 (SD 5.1), mean age was 44.4 years (SD 11.1) and 53% were female. As compared to normal weight beneficiaries, overweight beneficiaries had 23% greater adjusted odds of doctor shopping (OR 1.23, 95%CI 1.04–1.46) and obese beneficiaries had 52% greater adjusted odds of doctor shopping (OR 1.52, 95%CI 1.26–1.82). As compared to normal weight non-shoppers, overweight and obese shoppers had higher rates of ED visits (IRR 1.85, 95%CI 1.37–2.45; IRR 1.83, 95%CI 1.34–2.50, respectively), which persisted during within weight group comparisons (Overweight IRR 1.50, 95%CI 1.10–2.03; Obese IRR 1.54, 95%CI 1.12–2.11). Frequently changing PCPs may impair continuity and result in increased healthcare utilization.
PMCID: PMC3742565  PMID: 23671015
11.  Treatment with a SOD mimetic reduces visceral adiposity, adipocyte death and adipose tissue inflammation in high fat fed mice 
Obesity (Silver Spring, Md.)  2013;22(1):178-187.
Obesity is associated with enhanced reactive oxygen species (ROS) accumulation in adipose tissue. However, a causal role for ROS in adipose tissue expansion after high fat feeding is not established. The aim of this study is to investigate the effect of the cell permeable superoxide dismutase mimetic and peroxynitrite scavenger Mn(III)tetrakis(4-benzoic acid)porphyrin chloride (MnTBAP) on adipose tissue expansion and remodeling in response to high fat diet (HFD) in mice.
Design and Methods
Male C57BL/6j mice were fed normal chow or high fat diet (HFD) and treated with saline or MnTBAP for 5 weeks. The effects of MnTBAP on body weights, whole body energy expenditure, adipose tissue morphology and gene expression were determined.
MnTBAP attenuated weight gain and adiposity through a reduction in adipocyte hypertrophy, adipogenesis and fatty acid uptake in epididymal (eWAT) but not in inguinal (iWAT) white adipose tissue. Furthermore, MnTBAP reduced adipocyte death and inflammation in eWAT and diminished circulating levels of free fatty acids and leptin. Despite these improvements, the development of systemic insulin resistance and diabetes after HFD was not prevented with MnTBAP treatment.
Taken together, these data suggest a causal role for ROS in the development of diet-induced visceral adiposity but not in the development of insulin resistance and type 2 diabetes.
PMCID: PMC3758415  PMID: 23526686
Adipose tissue; adipogenesis; oxidative stress; superoxide dismutase; mitochondrial dysfunction; insulin resistance
12.  Relationship of food addiction to weight loss and attrition during obesity treatment 
Obesity (Silver Spring, Md.)  2013;22(1):52-55.
This study prospectively examined the relationship between food addiction (FA) and weight and attrition outcomes in overweight and obese adults participating in weight loss interventions.
Design and Methods
Participants were 178 adults (51.2±11.7 y, 36.1±4.8 kg/m2) in one of two outpatient weight-loss treatment programs for approximately six months. The Yale Food Addiction Scale (YFAS) assessed FA diagnosis and symptom count. The relationship between FA and weight loss and attrition was assessed.
After controlling for treatment arm, gender and baseline weight, there was no effect of FA status on weight loss (p=0.17) or attrition (p=0.37). Similarly, baseline FA symptom count was not associated with weight loss (p=0.14) or attrition (p=0.10).
Neither FA status nor symptom count affects weight loss or attrition during weight loss treatment.
PMCID: PMC3784622  PMID: 23776067
food addiction; weight loss; attrition
13.  Food reinforcement, dietary disinhibition and weight gain in non-obese adults 
Obesity (Silver Spring, Md.)  2013;22(1):254-259.
Food reinforcement is cross-sectionally related to body mass index and energy intake in adults, and prospectively predicts weight gain in children, but there has not been any research studying food reinforcement as a predictor of adult weight gain.
Design and Methods
This study examined whether the relative reinforcing value of food versus sedentary activities, as measured on a progressive ratio schedule, predicts 12 month weight gain. Dietary disinhibition and dietary restraint were also examined as potential moderators of this relationship, in a sample of 115 non-obese (Body Mass Index< 30) adults.
In a hierarchical regression controlling for baseline age and weight, dietary hunger, income, sex and minority status, food reinforcement significantly increased the variance from 6.3% to 11.7% (p = 0.01) and predicted weight gain (p = 0.01). Dietary disinhibition moderated this relationship (p = 0.02) and increased the variance an additional 4.7% (p = 0.02), such that individuals with high food reinforcement had greater weight gain if they were also high in disinhibition.
These results suggest that food reinforcement is a significant contributor to weight change over time, and food reinforcement may have the biggest effect on those who are most responsive to food cues.
PMCID: PMC3815500  PMID: 23512958
14.  Short-term Weight Loss Patterns, Baseline Predictors, and Longer-term Follow-up within a Randomized Controlled Trial 
Obesity (Silver Spring, Md.)  2013;22(1):45-51.
To examine weight loss patterns and predictors among participants in a primary care-based translation study of the Diabetes Prevention Program lifestyle intervention.
Design and Methods
Cluster analysis identified short-term (12-week) weight loss patterns among 72 intervention participants. Analysis of variance assessed cluster differences in weight loss maintenance at 15-month follow-up. Discriminant analysis identified baseline characteristics that best differentiated between clusters.
Participants had baseline mean (SD) age of 55.0 (10.8) years and BMI of 31.9 (5.2) kg/m2. Cluster analysis identified three short-term weight loss patterns: modest (n=15; 21%), moderate-and-steady (n=43; 60%), and substantial-and-early (n=14; 19%). Only participants with the latter two patterns achieved clinically significant (≥ 5%) short-term weight loss and maintained it at 15 months. On discriminant analysis, the modest cluster was most differentiated from other clusters by high friend encouragement for dietary change, high obesity-related problems, and low physical well-being. The moderate-and-steady cluster was differentiated by lower physical activity, family encouragement, and depression symptoms.
Results provide insight into the heterogeneity of response to an effective lifestyle intervention by identifying short-term weight loss patterns and their baseline predictors and relationship to 15-month success. If replicated, results may help tailor strategies for participant subgroups in weight loss programs.
PMCID: PMC3815705  PMID: 23740619
Overweight; obesity; weight loss; cluster analysis; discriminant analysis; randomized controlled trial
15.  Greater Weight Loss with Increasing Age in the Weight Loss Maintenance Trial 
Obesity (Silver Spring, Md.)  2013;22(1):39-44.
To determine the effect of age on weight loss and weight loss maintenance in participants in the Weight Loss Maintenance trial (WLM).
Design and Methods
We conducted secondary analysis of a randomized controlled trial of overweight/obese adults with CVD risk factors. Participants were 1685 adults with baseline BMI 25–45 kg/m2 with hypertension and/or dyslipidemia. Those who lost at least 4kg in an initial 6-month behavioral weight loss intervention (N=1032) were randomly assigned to a 30-month maintenance phase of self-directed control (SD), monthly personal counseling (PC), or unlimited access to an internet-based intervention (IT). Age groups were defined post-hoc and weight change was compared among age groups.
Participants ≥ 60 years old initially lost more weight than younger individuals, and sustained greater weight loss in IT and PC but not in SD (p-value for trend 0.024, 0.002, and 0.36, respectively).
In WLM, adults age ≥ 60 years had greater initial weight loss and greater sustained weight loss over 3 years, compared to younger adults. Older adults had greater weight loss maintenance with either personal counseling or internet-based intervention. Future research should determine optimal implementation strategies and effects of weight loss on health outcomes in older adults.
PMCID: PMC3849225  PMID: 23640912
obesity; weight loss; behavioral intervention; aging; older adults
16.  The Progression of Cardiometabolic Disease: Validation of a New Cardiometabolic Disease Staging System Applicable to Obesity 
Obesity (Silver Spring, Md.)  2013;22(1):110-118.
To validate a Cardiometabolic Disease Staging (CMDS) system for assigning risk level for diabetes, and all-cause and cardiovascular disease (CVD) mortality.
Design, and Methods
Two large national cohorts, CARDIA and NHANES III, were used to validate CMDS. CMDS: Stage 0: metabolically healthy; Stage 1: 1 or 2 Metabolic Syndrome risk factors (other than IFG); Stage 2: IFG or IGT or Metabolic Syndrome (without IFG); Stage 3: 2 of 3 (IFG, IGT, and/or Metabolic Syndrome); Stage 4: T2DM/CVD.
In the CARDIA study, compared with Stage 0 metabolically healthy subjects, adjusted risk for diabetes exponentially increased from Stage 1 (HR 2.83, 95% CI 1.76–4.55), to Stage 2 (HR 8.06, 95% CI 4.91–13.2), to Stage 3 (HR 23.5, 95% CI 13.7–40.1) (p for trend <0.001). In NHANES III, both cumulative incidence and multivariable adjusted hazard ratios markedly increased for both all-cause and CVD mortality with advancement of the risk stage from Stage 0 to 4. Adjustment for BMI minimally affected the risks for diabetes and all-cause/CVD mortality using CMDS.
CMDS can discriminate a wide range of risk for diabetes, CVD mortality, and all-cause mortality independent of BMI, and should be studied as a risk assessment tool to guide interventions that prevent and treat cardiometabolic disease.
PMCID: PMC3866217  PMID: 23894121
17.  The Geographic Distribution of Obesity in the US and the Potential Regional Differences in Misreporting of Obesity 
Obesity (Silver Spring, Md.)  2013;22(1):300-306.
State-level estimates of obesity based on self-reported height and weight suggest a geographic pattern of greater obesity in the Southeastern US; however, the reliability of the ranking among these estimates assumes errors in self-reporting of height and weight are unrelated to geographic region.
Design and Methods
We estimated regional and state-level prevalence of obesity (body mass index ≥ 30 kg/m2) for non-Hispanic black and white participants aged 45 and over were made from multiple sources: 1) self-reported from the Behavioral Risk Factor Surveillance System (BRFSS 2003-2006) (n = 677,425), 2) self-reported and direct measures from the National Health and Nutrition Examination Study (NHANES 2003-2008) (n = 6,615 and 6,138 respectively), and 3) direct measures from the REasons for Geographic and Racial Differences in Stroke (REGARDS 2003-2007) study (n = 30,239).
Data from BRFSS suggest that the highest prevalence of obesity is in the East South Central Census division; however, direct measures suggest higher prevalence in the West North Central and East North Central Census divisions. The regions relative ranking of obesity prevalence differs substantially between self-reported and directly measured height and weight.
Geographic patterns in the prevalence of obesity based on self-reported height and weight may be misleading, and have implications for current policy proposals.
PMCID: PMC3866220  PMID: 23512879
Obesity; geographic patterns
18.  Meal replacements, reduced energy density eating and weight loss maintenance in primary care patients: A randomized controlled trial 
Obesity (Silver Spring, Md.)  2013;22(1):94-100.
To compare the presence or absence of meal replacements (MRs) and an energy density (ED) intervention to facilitate weight loss maintenance.
Design and Methods
238 overweight primary care patients (mean BMI= 39.5 kg/m2) began the study; 132 completed the 12-week weight loss phase. Participants were randomly assigned to one of four maintenance conditions formed by crossing the presence or absence of MRs (MR+/MR−) and of the ED program (ED+/ED−) during a subsequent 9-month maintenance phase. Follow-ups assessments occurred 1 and 2 years after treatment termination.
Participants initially lost 6.1 kg. Analyses of variance based on weight change from the beginning of the maintenance phase to the 2-year follow-up produced a significant interaction. All groups except ED+/MR− regained substantial weight during follow-up; the ED+/MR− group regained significantly less weight than the control group at both follow-up assessments. No significant effects of treatment were found for several variables that were expected to mediate these outcomes.
Because weight losses achieved in lifestyle change programs for obesity are rarely maintained, the superior outcome achieved by the ED+/MR− condition is notable. Nonetheless, methodological issues and inability to identify a potential mediator of this outcome makes replication of this finding essential.
PMCID: PMC3869862  PMID: 23894101
obesity; maintenance; weight loss; energy density; meal replacements
19.  Short-term overeating results in incomplete energy intake compensation regardless of energy density or macronutrient composition 
Obesity (Silver Spring, Md.)  2013;22(1):119-130.
To evaluate the effects of overeating (140% of energy requirements) a high-fat low-energy density diet (HF/LED, 1.05kcal/g), high-fat high-energy density diet (HF/HED, 1.60kcal/g), and high-carbohydrate (HC) LED (1.05kcal/g) for 2-days on subsequent 4-day energy intake (EI), activity levels, appetite, and mood.
Design and Methods
Using a randomized cross-over design, energy expenditure and EI were standardized during overeating.
In 20 adults with a mean±SD BMI of 30.7±4.6kg/m2, EI was not suppressed until the second day after overeating and accounted for ~30% of the excess EI. Reductions in EI did not differ among the 3 diets or across days. Overeating had no effect on subsequent energy expenditure but steps/day decreased after the HC/LED and HF/HED. Sleep time was increased after the HF/HED compared to both LEDs. After overeating a HF/HED vs. HF/LED, carbohydrate cravings, hunger, prospective food consumption, and sadness increased and satisfaction, relaxation, and tranquility decreased.
Diet type, time, or their interaction had no impact on compensation over 4 days. No adaptive thermogenesis was observed. The HF/HED vs. HF/LED had detrimental effects on food cravings, appetite, and mood. These results suggest short-term overeating is associated with incomplete compensation.
PMCID: PMC3873377  PMID: 23913807
hyperphagia; appetite; spontaneous physical activity; energy expenditure; hunger; sleep
20.  Weight Loss after Bariatric Surgery in Morbidly Obese Adolescents with MC4R mutations 
Obesity (Silver Spring, Md.)  2013;22(1):225-231.
To determine the frequency of Melanocortin4 Receptor (MC4R) mutations in morbidly obese adolescents undergoing bariatric surgery and compare weight loss outcomes in patients with and without mutations.
Design and Methods
In this prospective cohort study, 135 adolescent patients evaluated for bariatric surgery were screened for MC4R mutations; 56 had 12 month postoperative data available for analysis.
MC4R mutations were detected in five of the 135 patients (3.7%); four underwent restrictive bariatric surgery. For the three patients with gastric banding, percent excess weight loss (%EWL) postoperatively was 36.0% at 5 years in one, 47% at 4 years in the second, and 85% at 1 year in the third. For the patient with gastric sleeve resection, %EWL of 96% was attained at 1 year postoperatively. The four MC4R cases had a higher, although non-significant, %EWL compared to 52 non-matched controls at 12 months postoperatively (48.6% vs. 23.4%; p<0.37). When matched by age, sex, and race to 14 controls, there was no significant difference in %EWL (p < 0.31), BMI change (p< 0.27), or absolute weight loss (p <0.20).
The frequency of MC4R mutations is similar to prior studies, with affected patients showing beneficial weight loss outcomes.
PMCID: PMC3880391  PMID: 23740648
MC4R; Obesity; Adolescents; Bariatric surgery
21.  Eight-Year Weight Losses with an Intensive Lifestyle Intervention: The Look AHEAD Study 
Obesity (Silver Spring, Md.)  2014;22(1):5-13.
To evaluate 8-year weight losses achieved with intensive lifestyle intervention (ILI) in the Look AHEAD (Action for Health in Diabetes) study.
Design and Methods
Look AHEAD assessed the effects of intentional weight loss on cardiovascular morbidity and mortality in 5,145 overweight/obese adults with type 2 diabetes, randomly assigned to ILI or usual care (i.e., diabetes support and education [DSE]). The ILI provided comprehensive behavioral weight loss counseling over 8 years; DSE participants received periodic group education only.
All participants had the opportunity to complete 8 years of intervention before Look AHEAD was halted in September 2012; ≥88% of both groups completed the 8-year outcomes assessment. ILI and DSE participants lost (mean±SE) 4.7±0.2% and 2.1±0.2% of initial weight, respectively (p<0.001) at year 8; 50.3% and 35.7%, respectively, lost ≥5% (p<0.001), and 26.9% and 17.2%, respectively, lost ≥10% (p<0.001). Across the 8 years ILI participants, compared with DSE, reported greater practice of several key weight-control behaviors. These behaviors also distinguished ILI participants who lost ≥10% and kept it off from those who lost but regained.
Look AHEAD’s ILI produced clinically meaningful weight loss (≥5%) at year 8 in 50% of patients with type 2 diabetes and can be used to manage other obesity-related co-morbid conditions.
Trial Registration Identifier: NCT00017953
PMCID: PMC3904491  PMID: 24307184
22.  Baseline Predictors of Missed Visits in the Look AHEAD Study 
Obesity (Silver Spring, Md.)  2014;22(1):131-140.
To identify baseline attributes associated with consecutively missed data collection visits during the first 48 months of Look AHEAD—a randomized, controlled trial in 5145 overweight/obese adults with type 2 diabetes designed to determine the long-term health benefits of weight loss achieved by lifestyle change.
Design and Methods
The analyzed sample consisted of 5016 participants who were alive at month 48 and enrolled at Look AHEAD sites. Demographic, baseline behavior, psychosocial factors, and treatment randomization were included as predictors of missed consecutive visits in proportional hazard models.
In multivariate Cox proportional hazard models, baseline attributes of participants who missed consecutive visits (n=222) included: younger age ( Hazard Ratio [HR] 1.18 per 5 years younger; 95% Confidence Interval 1.05, 1.30), higher depression score (HR 1.04; 1.01, 1.06), non-married status (HR 1.37; 1.04, 1.82), never self-weighing prior to enrollment (HR 2.01; 1.25, 3.23), and randomization to minimal vs. intensive lifestyle intervention (HR 1.46; 1.11, 1.91).
Younger age, symptoms of depression, non-married status, never self-weighing, and randomization to minimal intervention were associated with a higher likelihood of missing consecutive data collection visits, even in a high-retention trial like Look AHEAD. Whether modifications to screening or retention efforts targeted to these attributes might enhance long-term retention in behavioral trials requires further investigation.
PMCID: PMC3943994  PMID: 23996977
randomized clinical trials; behavioral trial; retention; obesity
23.  Relapse to Smoking and Postpartum Weight Retention Among Women Who Quit Smoking During Pregnancy 
Obesity (Silver Spring, Md.)  2011;20(2):457-459.
Postpartum weight retention contributes to obesity risk in women. Given that most women who quit smoking as a result of pregnancy will resume smoking within 6 months postpartum and that there is a robust association between smoking and weight, we sought to evaluate postpartum weight retention as a function of postpartum smoking status among women who had quit smoking during pregnancy. Women (N = 183) with biochemically confirmed cigarette abstinence at the end of pregnancy were recruited between February 2003 and November 2006. Women self-reported demographic information and weight before pregnancy. Smoking status and weight were documented at the end of pregnancy and at 6, 12, and 24 weeks postpartum. Breastfeeding was reported at 6 weeks postpartum. Differences in weight retention by relapse status at each assessment were evaluated. To examine weight retention in the presence of conceptually relevant covariates, mixed models with log-transformed weight data were used. At 24 weeks postpartum, 34.6% of women remained abstinent. Women who remained abstinent throughout the 24-week period retained 4.7 ± 2.1 kg more than did women who had relapsed by 6 weeks postpartum, P = 0.03. This difference in postpartum weight retention was significant after controlling for relevant covariates (age, race, breastfeeding, and pregravid BMI). Resumption of smoking within the first 6 weeks following childbirth is associated with decreased postpartum weight retention, even after controlling for breastfeeding and pregravid weight. Interventions to sustain smoking abstinence postpartum might be enhanced by components designed to minimize weight retention.
PMCID: PMC4076786  PMID: 22076594
24.  Beliefs About Weight Gain Among Young Adults: Potential Challenges to Prevention 
Obesity (Silver Spring, Md.)  2011;19(9):1901-1904.
This study assessed young adults’ beliefs about weight gain with the goal of improving intervention efforts with this high-risk group. A total of 1,347 incoming freshman (45% male; 81% non-Hispanic white; 18.6 ± 1.7 years; BMI = 23.3 ± 2.3 kg/m2) at a large state university in the Northeast completed a survey designed to assess: (i) degree of concern about weight gain, (ii) level of interest in weight control programs, and (iii) the most acceptable setting for an intervention. Perceptions about freshman weight gain were consistent across gender, with men and women reporting that the average student gains 5.4 ± 1.9 kg and 5.6 ± 1.9 kg respectively. Men in general were less concerned about weight gain (P < 0.001) and reported they would have to gain 6.2 ± 4.2 kg before becoming concerned compared to 3.1 ± 1.7 kg among women (P < 0.001). Overweight (OW) men were more concerned about gaining weight than normal weight (NW) men (P < 0.001) and indicated they would have to gain less weight before becoming concerned (5.0 ± 3.0 kg vs. 6.7 ± 4.5 kg, P < 0.001). Fewer men reported they would join a program to prevent weight gain (17% men vs. 40% women, P < 0.001); the percentage of men willing to join a prevention program did not vary by weight status (P = 0.59). Both men and women were most likely to report a willingness to attend classes on a local college campus compared to other settings. Findings highlight the challenges of engaging young adults in weight gain prevention programs, particularly young men, and are discussed in terms of implications for improving recruitment efforts and intervention development with this population.
PMCID: PMC4067457  PMID: 21738239
25.  Improved Memory Function Two Years After Bariatric Surgery 
Obesity (Silver Spring, Md.)  2013;22(1):32-38.
Obesity is as an independent risk factor for poor neurocognitive outcomes, including Alzheimer’s disease. Bariatric surgery has recently been shown to result in improved memory at 12-weeks post-operatively. However, the long-term effects of bariatric surgery on cognitive function remain unclear.
Design and Methods
86 individuals (63 bariatric surgery patients, 23 obese controls) were recruited from a prospective study examining the neurocognitive effects of bariatric surgery. All participants completed self-report measurements and a computerized cognitive test battery prior to surgery and at 12-week and 24-month follow-up; obese controls completed measures at equivalent time points.
Bariatric surgery patients exhibited high rates of pre-operative cognitive impairments in attention, executive function, memory, and language. Relative to obese controls, repeated measures ANOVA showed improvements in memory from baseline to 12-weeks and 24-months post-operatively (p < .05). Regression analyses controlling for baseline factors revealed that a lower BMI at 24-months demonstrated a trend toward significance for improved memory (β = -.30, p = .075).
These findings suggest that cognitive benefits of bariatric surgery may extend to 24-months post-operatively. Larger prospective studies with extended follow-up periods are needed to elucidate whether bariatric surgery decreases risk for cognitive decline and possibly the development of dementia.
PMCID: PMC4054602  PMID: 23625587
Obesity; bariatric surgery; cognitive function; weight loss

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