Obesity‐related Comorbidities in Obese African Americans in an Outpatient Weight Loss Program

Objective: To identify, among obese African‐American enrollees in an outpatient weight loss program, differences between those with and without obesity‐related comorbidities (ORCMs). Research Methods and Procedures: Data were from 237 obese African Americans (BMI, 30 to 50 kg/m²; 90% women) who enrolled in a 10‐week lifestyle weight loss program. Analyses compared subgroups defined by ORCM status (from medical history) on baseline characteristics, program attendance, and postprogram weight change. Results: Most participants (76%) had one or more ORCMs. Those with versus without ORCMs, respectively, were older (mean age, 45.6 vs. 37.1 years; p < 0.001), were less educated (59.2% vs. 76.6% with >12 years; p = 0.031), were more likely to perceive a physical limitation affecting activity (22.2% vs. 1.8%; p < 0.001), and had higher waist circumference (mean, 113.7 vs. 106.9 cm; p < 0.001) but not BMI (38.3 vs. 37.0 kg/m²; p = 0.095). Logistic regression analyses confirmed the independence of these associations. Having ORCMs was not associated with class attendance or return for data collection after the 10‐week program. Postprogram weight change (n = 134) was unrelated to ORCMs, but better weight loss was seen among those without perceived physical limitations (1.9 vs. 0.4 kg in those without versus with limitations; p = 0.069). Conclusion: Data from this clinical sample of obese African Americans suggest that waist circumference is relevant to ORCM status at BMI levels up to 50 kg/m². Clear indications for tailoring of treatment based on ORCM status were not identified, although the possible influence of ORCM‐related activity limitations warrants further study.     

Vertebral Bone Marrow Fat Is Positively Associated With Visceral Fat and Inversely Associated With IGF‐1 in Obese Women

Recent studies have demonstrated an important physiologic link between bone and fat. Bone and fat cells arise from the same mesenchymal precursor cell within bone marrow, capable of differentiation into adipocytes or osteoblasts. Increased BMI appears to protect against osteoporosis. However, recent studies have suggested detrimental effects of visceral fat on bone health. Increased visceral fat may also be associated with decreased growth hormone (GH) and insulin‐like growth factor 1 (IGF‐1) levels which are important for maintenance of bone homeostasis. The purpose of our study was to assess the relationship between vertebral bone marrow fat and trabecular bone mineral density (BMD), abdominal fat depots, GH and IGF‐1 in premenopausal women with obesity. We studied 47 premenopausal women of various BMI (range: 18–41 kg/m², mean 30 ± 7 kg/m²) who underwent vertebral bone marrow fat measurement with proton magnetic resonance spectroscopy (1H‐MRS), body composition, and trabecular BMD measurement with computed tomography (CT), and GH and IGF‐1 levels. Women with high visceral fat had higher bone marrow fat than women with low visceral fat. There was a positive correlation between bone marrow fat and visceral fat, independent of BMD. There was an inverse association between vertebral bone marrow fat and trabecular BMD. Vertebral bone marrow fat was also inversely associated with IGF‐1, independent of visceral fat. Our study showed that vertebral bone marrow fat is positively associated with visceral fat and inversely associated with IGF‐1 and BMD. This suggests that the detrimental effect of visceral fat on bone health may be mediated in part by IGF‐1 as an important regulator of the fat and bone lineage.     

Sex‐dependent Associations of Leptin With Metabolic Syndrome–related Variables: The Stanislas Study

Serum leptin has been reported to be associated in a sex‐dependent manner with C‐reactive protein (CRP), independently of adiposity. We tested the hypothesis that leptin is associated, independently of anthropometry indexes and in a sex‐dependent way, with other inflammatory markers and variables related to metabolic syndrome (MS). In 384 healthy middle‐aged adults (192 men and 192 women) total fat mass (FM), waist circumference (WC), serum leptin and 15 MS‐related parameters (systolic and diastolic blood pressure, triglycerides, cholesterol, high density lipoprotein (HDL)‐cholesterol, apo AI and B, fasting glucose, uric acid, CRP, orosomucoid and haptoglobin levels and aspartate aminotransferase (ASAT), alanine aminotransferase (ALAT) and γ‐glutamyl transferase (GGT) activities) were measured. After adjustment for age, alcohol and cigarette consumption, WC, and total FM, leptin concentration was significantly associated with serum triglycerides, total cholesterol, apo B, uric acid and haptoglobin concentrations and liver enzyme activity only in men, and with apo AI, HDL‐cholesterol (only borderline) and CRP only in women. Sex interaction terms were significant for total cholesterol, apo B, HDL cholesterol, uric acid, ALAT and GGT, and borderline significant for triglycerides, apo AI and ASAT. In this healthy population, leptin is significantly associated with various MS factors, independently of WC and total FM, depending on gender. Our study provides further evidence of sex‐related differences mediated by leptin in inflammatory mechanisms and other MS‐related metabolic pathways.     

Low Plasma Leptin Concentration and Low Rates of Fat Oxidation in Weight‐Stable Post‐Obese Subjects

Objective: A low resting metabolic rate for a given body size and composition, a low rate of fat oxidation, low levels of physical activity, and low plasma leptin concentrations are all risk factors for body weight gain. The aim of the present investigation was to compare resting metabolic rate (RMR), respiratory quotient (RQ), levels of physical activity, and plasma leptin concentrations in eight post‐obese adults (2 males and 6 females; 48.9 ± 12.2 years; body mass index [BMI]: 24.5 ± 1.0 kg/m²; body fat 33 ± 5%; mean ± SD) who lost 27.1 ± 21.3 kg (16 to 79 kg) and had maintained this weight loss for ≥2 months (2 to 9 months) to eight age‐ and BMI‐matched control never‐obese subjects (1 male and 7 females; 49.1 ± 5.2 years; BMI 24.4 ± 1.0 kg/m²; body fat 33 ± 7%). Research Methods and Procedures: Following 3 days of weight maintenance diet (50% carbohydrate and 30% fat), RMR and RQ were measured after a 10‐hour fast using indirect calorimetry and plasma leptin concentrations were measured using radioimmunoassay. Levels of physical activity were estimated using an accelerometer over a 48‐hour period in free living conditions. Results: After adjustment for fat mass and fat‐free mass, post‐obese subjects had, compared with controls, similar levels of physical activity (4185 ± 205 vs. 4295 ± 204 counts) and similar RMR (1383 ± 268 vs. 1430 ± 104 kcal/day) but higher RQ (0.86 ± 0.04 vs. 0.81 ± 0.03, p < 0.05). Leptin concentration correlated positively with percent body fat (r = 0.57, p < 0.05) and, after adjusting for fat mass and fat‐free mass, was lower in post‐obese than in control subjects (4.5 ± 2.1 vs. 11.6 ± 7.9 ng/mL, p < 0.05). Discussion: The low fat oxidation and low plasma leptin concentrations observed in post‐obese individuals may, in part, explain their propensity to relapse.     

Linkage and Genome‐wide Association Analysis of Obesity‐related Phenotypes: Association of Weight With the MGAT1 Gene

As major risk‐factors for diabetes and cardiovascular diseases, the genetic contribution to obesity‐related traits has been of interest for decades. Recently, a limited number of common genetic variants, which have replicated in different populations, have been identified. One approach to increase the statistical power in genetic mapping studies is to focus on populations with increased levels of linkage disequilibrium (LD) and reduced genetic diversity. We have performed joint linkage and genome‐wide association analyses for weight and BMI in 3,448 (linkage) and 3,925 (association) partly overlapping healthy individuals from five European populations. A total of four chromosomal regions (two for weight and two for BMI) showed suggestive linkage (lod >2.69) either in one of the populations or in the joint data. At the genome‐wide level (nominal P < 1.6 × 10^?7, Bonferroni‐adjusted P < 0.05) one single‐nucleotide polymorphism (SNP) (rs12517906) (nominal P = 7.3 × 10^?8) was associated with weight, whereas none with BMI. The SNP associated with weight is located close to MGAT1. The monoacylglycerol acyltransferase (MGAT) enzyme family is known to be involved in dietary fat absorption. There was no overlap between the linkage regions and the associated SNPs. Our results show that genetic effects influencing weight and BMI are shared across diverse European populations, even though some of these populations have experienced recent population bottlenecks and/or been affected by genetic drift. The analysis enabled us to identify a new candidate gene, MGAT1, associated with weight in women.     

Associations of Fat Distribution and Obesity with Hypertension in a Bi‐ethnic Population: The ARIC Study

Objective: To examine associations of hypertension with obesity and fat distribution among African American and white men and women. Research Methods and Procedures: The analysis sample included 15,063 African American and white men and women between the ages of 45 and 64 years who were participants in the 1987 through 1989 examination of the Atherosclerosis Risk in Communities Study (ARIC). Odds ratios and adjusted prevalences of hypertension were calculated across sexspecific quintiles of body mass index (BMI), waist‐to‐hip ratio (WHR), waist circumference, and waist‐to‐height ratio (waist/height) and adjusted for age, research center, smoking, education, physical activity, alcohol consumption, hormone replacement therapy, and menopausal status. Results: The prevalence of hypertension was higher among African Americans than whites. In the lowest quintile of BMI, 41% of African American women and 43% of African American men had hypertension compared with 14% of white women and 19% of white men. Elevated BMI, WHR, waist circumference, and waist/height were associated with increased odds of hypertension in African American and white men and women. In women, but not in men, there were significant interactions between ethnicity and the anthropometric variables studied here. The direction of the interaction indicated larger odds ratios for hypertension with increasing levels of anthropometric indices in white compared with African American women. Discussion: Obesity and abdominal fat preponderance were associated with increased prevalence of hypertension in African American and white men and women. Associations were similar among African American and white men, but obesity and fat patterning were less strongly associated with hypertension in African American than in white women.     

Fat Compartments and Apolipoprotein B‐100 Kinetics in Overweight‐Obese Men

Objective: To examine the association between the kinetics of very‐low‐density‐lipoprotein (VLDL)‐apolipoprotein B‐100 (apoB) and intraperitoneal, retroperitoneal, subcutaneous abdominal, and total adipose tissue masses (IPATM, RPATM, SAATM, and TATM, respectively) in overweight/obese men. Research Methods and Procedures: Hepatic secretion of VLDL was measured using an intravenous infusion of 1‐[¹³C]‐leucine in 51 men with a wide range of body mass index (25.1 to 42.2 kg/m²). Isotopic enrichment of VLDL‐apoB was measured using gas chromatography‐mass spectrometry and a multicompartmental model used to estimate VLDL‐apoB metabolic parameters. IPATM, RPATM, and SAATM (kilograms) were quantified between T11 and S1 using magnetic resonance imaging; TATM (kilograms) was determined using bioelectrical impedance. Insulin resistance was estimated by homeostasis model assessment (HOMA) score. Results: In stepwise regression, IPATM was the best predictor of hepatic secretion of VLDL‐apoB (r = 0.390, p < 0.005) and TATM was the best predictor of VLDL‐apoB fractional catabolic rate (r = 0.282, p < 0.05). IPATM remained significantly associated with VLDL‐apoB secretion after adjusting for TATM or HOMA score (r = 0.360, p < 0.01 and r = 0.310, p < 0.05, respectively). This association was also independent of age, dietary intake, and body mass index. None of the fat compartments were significantly associated with the fractional catabolic rate of VLDL‐apoB after adjusting for HOMA score. Discussion: In overweight/obese men, the quantity of both IPATM and TATM determine the kinetics of VLDL‐apoB. The effect of IPATM on VLDL‐apoB secretion is independent of both total fat mass and the degree of insulin resistance.     

Admixture Mapping of Obesity‐related Traits in African Americans: The Atherosclerosis Risk in Communities (ARIC) Study

Obesity is an important cause of morbidity and mortality worldwide. In the United States, the prevalence of obesity is higher in African Americans than whites, even after adjustment for socioeconomic status (SES). This leads to the hypothesis that differences in genetic background may contribute to racial/ethnic differences in obesity‐related traits. We tested this hypothesis by conducting a genome‐wide admixture mapping scan using 1,350 ancestry‐informative single‐nucleotide polymorphisms (SNPs) in 3,531 self‐identified blacks from the Atherosclerosis Risk in Communities (ARIC) study. We used these markers to estimate the overall proportions of European ancestry (PEAs) for each individual and then scanned for the association between PEA and obesity‐related traits (both continuous and dichotomous) at each locus. The median (interquartile range) PEA was 0.151 (0.115). PEA was inversely correlated with continuous BMI, weight, and subscapular skinfold thickness, even after adjusting for socioeconomic factors. In contrast, PEA was positively correlated with BMI‐adjusted waist circumference. Using admixture mapping on dichotomized traits, we identified a locus on 2p23.3 to be suggestively associated with BMI (locus‐specific lod = 4.11) and weight (locus‐specific lod = 4.07). After adjusting for global PEA, each additional copy of a European ancestral allele at the 2p23.3 peak was associated with a BMI decrease of ～0.92 kg/m² (P = 2.9 × 10^?5). Further mapping in this region on chromosome 2 may be able to uncover causative variants underlying obesity, which may offer insights into the control of energy homeostasis.     

Obesity‐Related Knowledge,Attitudes, and Behaviors in Obese and Non‐obese Urban Philadelphia Female Adolescents

Objectives: To examine relationships between knowledge, attitudinal and behavioral factors, and obesity and to determine how these factors influence obesity status in west Philadelphia female adolescents. Research Methods and Procedures: A matched‐pairs study was conducted with 32 stature‐ and age‐matched pairs of obese (body mass index and triceps skinfold ≥95th percentile of National Health and Nutrition Examination Survey I) and non‐obese (body mass index and triceps skinfold between the 15th and 85th percentiles of National Health and Nutrition Examination Survey I) female African American adolescents (aged 11 to 15 years), selected from a school‐based study sample, based on obesity status and matching criteria. Adolescents were compared on the following measures: physical activity, inactivity, dietary intake, eating attitudes, health behavior knowledge, body image, self‐esteem, and maturation status. Differences between obese and non‐obese females were tested using paired t tests and Wilcoxon matched‐pairs signed‐rank tests. Results: Physical activity, inactivity, and perception of ideal body size emerged as the most important contributory factors to obesity status. There were no statistically significant matched‐pair differences in macronutrient and micronutrient intakes, self‐esteem, eating attitudes, health behavior knowledge, or maturation status of these adolescents. Obese adolescents had significantly lower levels of physical activity, higher inactivity, and a larger perception of ideal body size than non‐obese adolescents. Discussion: Knowledge and attitudinal factors (with the exception of perception of ideal body size) had far less association with obesity than activity‐related behavioral factors. These findings suggest that future intervention strategies should pay particular attention to physical activity, inactivity, and body image attitudes.     

COX‐2‐mediated Inflammation in Fat Is Crucial for Obesity‐linked Insulin Resistance and Fatty Liver

The aim was to examine the role of cyclooxygenase (COX)‐2‐mediated inflammation in the development of obese linked insulin resistance and fatty liver. The rats were fed separately regular diet (CONT), high‐fat diet (HFD) ad libitum, or energy restrictedly for 12 weeks. Rats fed HFD ad libitum were further divided into three subgroups co‐treated with vehicle (HFa), or a selective COX‐2 inhibitor celecoxib (HFa‐Cel) or mesulid (HFa‐Mes). Euglycemic hyperinsulinemic clamp (EHC) experiment was performed at the end of study. Another set of rats with similar grouping was further divided into those with a 4, 8, or 12‐week intervention period for hepatic sampling. Body weight was increased significantly and similarly in HFa, HFa‐Cel, and HFa‐Mes. Time‐dependent increases in plasma insulin, glucose, 8‐isoprostanes, leptin levels, homeostasis model assessment of insulin resistance (HOMA‐IR) and hepatic triglyceride contents shown in HFa were significantly reversed in HFa‐Cel and HFa‐Mes. During EHC period, the reduction in stimulation of whole body glucose uptake, suppression of hepatic glucose production and metabolic clearance rate of insulin shown in HFa were significantly reversed in HFa‐Cel and HFa‐Mes. The enhanced COX‐2 and tumor necrosis factor‐α (TNF‐α) but attenuated PPAR‐γ and C/EBP‐α mRNA expressions in epididymal fat shown in HFa were significantly reversed in HFa‐Cel and HFa‐Mes. The increases in average cell size of adipocytes and CD68 positive cells shown in HFa were also significantly reversed in HFa‐Cel and HFa‐Mes. Our findings suggest that COX‐2 activation in fat inflammation is important in the development of insulin resistance and fatty liver in high fat induced obese rats.     

Reexamining Obesigenic Families: Parents’ Obesity‐related Behaviors Predict Girls’ Change in BMI

Objective: It has been shown that girls from families in which mothers and fathers had high dietary intake and low physical activity (i.e., obesigenic families) were at increased risk of obesity from ages 5 to 7 years. This follow‐up study uses additional data collected when girls were 9 and 11 years old to examine whether girls from obesigenic families continued to show greater increases in BMI over time and reported unhealthy dietary and activity patterns. Research Methods and Procedures: Families from the original cohort were reexamined when girls were 9 and 11 years of age. Parents’ and girls’ BMI, dietary intake, and physical activity and girls’ percentage body fat and television viewing were assessed. Results: In comparison with girls from non‐obesigenic families, girls from obesigenic families showed greater increases in BMI and BMI z score from ages 5 to 7 years that were maintained across ages 7 to 11 years. Furthermore, girls from obesigenic families had higher percentage body fat at ages 9 and 11 years. These results were independent of parents’ BMI. Additional findings showed that girls from obesigenic families had diets higher in percentage fat and had higher levels of television viewing than girls from non‐obesigenic families. Discussion: The environment that parents create, by way of their own dietary and physical activity behaviors, may have a lasting negative effect on children's weight trajectories and their emerging obesity risk behaviors, such as their dietary patterns. These findings further highlight the importance of the family in establishing children's obesity risk and the necessity of targeting parents of young children in obesity prevention efforts.     

Adiponectin Levels during Low‐ and High‐Fat Eucaloric Diets in Lean and Obese Women

Objective: Adiponectin influences insulin sensitivity (S_I) and fat oxidation. Little is known about changes in adiponectin with changes in the fat content of eucaloric diets. We hypothesized that dietary fat content may influence adiponectin according to an individual's S_I. Research Methods and Procedures: We measured changes in adiponectin, insulin, glucose, and leptin in response to high‐fat (HF) and low‐fat (LF) eucaloric diets in lean (n = 10) and obese (n = 11) subjects. Obese subjects were further subdivided in relation to a priori S_I. Results: We found significantly higher insulin, glucose, and leptin and lower adiponectin in obese vs. lean subjects during both HF and LF. The mean group values of these measurements, including adiponectin (lean, HF 21.9 ± 9.8; LF, 20.8 ± 6.6; obese, HF 10.0 ± 3.3; LF, 9.5 ± 2.3 ng/mL; mean ± SD), did not significantly change between HF and LF diets. However, within the obese group, the insulin‐sensitive subjects had significantly higher adiponectin during HF than did the insulin‐resistant subjects. Additionally, the change in adiponectin from LF to HF diet correlated positively with the obese subjects’ baseline S_I. Discussion: Although in lean and obese women, group mean values for adiponectin did not change significantly with a change in fat content of a eucaloric diet, a priori measured S_I in obese subjects predicted an increase in adiponectin during the HF diet; this may be a mechanism that preserves S_I in an already obese group.     

Leptin,Insulin, and Obesity‐related Phenotypes: Genetic Influences on Levels and Longitudinal Changes

This study estimated the genetic and environmental determinants of plasma leptin and insulin levels and of obesity‐related phenotypes. Included in this analysis were family members from 80 families living in kibbutz settlements, who participated in two examinations 8–10 years apart. We estimated that polygenes explained 30–50% of the adjusted leptin and insulin levels and 30–70% of the anthropometric phenotypes. This study demonstrated a significant genetic influence on longitudinal changes in leptin and BMI (h² = 0.45) and small‐to‐moderate heritability estimates for changes in insulin and other obesity‐related phenotypes. In bivariate genetic analyses, we observed positive genetic correlations between leptin and anthropometric phenotypes, suggesting that shared effects of the same sets of loci account for 20–30% of the additive genetic variance in these pairs of variables. Shared genetic factors also account for 20–25% of the additive genetic variance in insulin—anthropometric pairs of variables.