Intramyocellular Lipid Content and Molecular Adaptations in Response to a 1‐Week High‐Fat Diet

Objective: To investigate molecular adaptations that accompany the elevation of intramyocellular lipid (IMCL) content on a high‐fat (HF) diet for 1 week. Research Methods and Procedures: Ten subjects consumed a normal‐fat (NF) diet for 1 week, followed by an HF diet for another week. After both dietary periods, we determined the IMCL content by proton magnetic resonance spectroscopy in the vastus lateralis muscle and quantified changes in gene expression, protein content, and activity in biopsy samples. We investigated genes involved in carbohydrate and fatty acid handling [lipoprotein lipase, acetyl‐coenzyme A carboxylase (ACC) 2, hormone‐sensitive lipase, hexokinase II, and glucose transporter 4] and measured protein levels of CD36 and phosphorylated and unphosphorylated ACC2 and the activity of adenosine monophosphate‐activated kinase. Results: IMCL content was increased by 54% after the HF period. Lipoprotein lipase mRNA concentration was increased by 33%, whereas ACC2 mRNA concentration tended to be increased after the HF diet. Hexokinase II, glucose transporter 4, and hormone‐sensitive lipase mRNA were unchanged after the HF diet. ACC2 and CD36 protein levels, phosphorylation status of ACC2, and adenosine monophosphate‐activated kinase activity did not change in response to the HF diet. Discussion: We found that IMCL content in skeletal muscle increased after 1 week of HF feeding, accompanied by molecular adaptations that favor fat storage in muscle rather than oxidation.     

Effect of Energy‐Reduced Diets High in Dairy Products and Fiber on Weight Loss in Obese Adults

Objective: Studies suggest that high‐dairy and high‐fiber/low‐glycemic index diets may facilitate weight loss, but data are conflicting. The effects on weight loss and body fat of a high‐dairy diet and a diet high in dairy and fiber and low in glycemic index were compared with a standard diet. Research Methods and Procedures: Ninety obese subjects were recruited into a randomized trial of three diets designed to provide a calorie deficit of 500 calories/d over a 48‐week period. The study compared a moderate (not low)‐calcium diet with a high‐calcium diet. Results: Seventy‐two subjects completed the study. Significant weight and fat loss occurred with all three diets. A diet with 1400 mg of calcium did not result in greater weight (11.8 ± 6.1 kg) or fat (9.0 ± 6.0 kg) loss than a diet with 800 mg of calcium (10.0 ± 6.8 and 7.5 ± 6.6 kg, respectively). A diet with 1400 mg of calcium, increased fiber content, and fewer high‐glycemic index foods did not result in greater weight (10.6 ± 6.8 kg) or fat (8.5 ± 7.8 kg) loss than the standard diet with 800 mg of calcium. Lipid profile, high‐sensitivity C‐reactive protein, leptin, fasting glucose, and insulin improved significantly, but there were no significant differences between the experimental diets and the control diet. Discussion: We found no evidence that diets higher than 800 mg of calcium in dairy products or higher in fiber and lower in glycemic index enhance weight reduction beyond what is seen with calorie restriction alone.     

Relationships Between Changes in Body Composition and Changes in Cardiovascular Risk Factors: The SOS Intervention Study

SJÖSTRÖM, C DAVID, LAUREN LISSNER, LARS SJÖSTROM. Relationships between changes in body composition and changes in cardiovascular risk factors: The SOS Intervention Study. Relationships between 2-year changes in body composition (estimated from computed tomography-validated anthropometry based on sagittal trunk diameter, weight, and height), adipose tissue (AT) distribution, and cardiovascular risk factors (blood pressure, lipids, glucose, insulin, uric acid) were examined in 842 treated adults with severe obesity with weight changes from ?95. 5 to +30. 6 kg. Although the change (Δ) of visceral AT mass (expressed in % total AT) for a given change in body mass index (ΔBMI) was 6-fold larger in men than in women, Δwaist and Δwaist/hip were similar in both sexes. In men, risk factor changes were similarly related to Awaist, Abodyweight, and ΔBMI, whereas in women, Δbodyweight seemed to be the single independent variable with the highest explanatory power. In multivariate regressions adjusted for ΔBMI and baseline conditions, Δvisceral AT mass was more strongly associated with risk factor changes than were Δwaist and ?waist/hip. When using a three-compartment model (lean body mass, subcutaneous and visceral AT masses) plus neck and thigh girths (indicators of subcutaneous AT distribution), risk factor changes were related both to ?subcutaneous and ?visceral AT masses but not to Δlean body mass. In agreement with cross-sectional findings, Δneck was positively and Δthigh was negatively related to some risk factor changes. Thus, the use of waist as a single risk factor indicator seems less effective for epidemiological studies than the simple anthropometric measures presented here, which are able to separate the effects of visceral AT mass, subcutaneous AT mass, and subcutaneous AT distribution on metabolic parameters under both cross-sectional and longitudinal conditions.     

Genetic and Environmental Influences on Body‐Fat Measures among African‐American Twins

Objective: To investigate the genetic and environmental influences on body‐fat measures including waist circumference (WC), waist‐to‐hip ratio (WHR), and body mass index (BMI) among African‐American men and women. Research Methods and Procedures: Measurements were taken as part of the Carolina African American Twin Study of Aging. This sample currently comprises 146 same‐sex African‐American twins with an average age of 50 years (range, 22 to 88 years). This analysis included 26 monozygotic and 29 dizygotic men and 45 monozygotic and 46 dizygotic women. Maximum likelihood quantitative genetic analysis was used. Results: In men, additive genetic effects accounted for 77% of the variance in WC, 59% in WHR, and 89% in BMI. In women, additive genetic effects accounted for 76% of the variance in WC, 56% in WHR, and 73% in BMI. The remaining variance in both men and women was attributed to unique environmental effects (WC, 21%; WHR, 36%; BMI, 11% in men and WC, 22%; WHR, 38%; BMI, 27% in women) and age (WC, 2%; WHR, 5% in men and WC, 2%; WHR, 6% in women). When BMI was controlled in the analysis of WC and WHR, it accounted for a portion of the genetic and environmental variance in WHR and over one‐half of the genetic and environmental variance in WC. Discussion: There are both genetic and environmental influences on WC, WHR, and BMI, and independent of BMI, there are genetic and environmental effects on WC and WHR among both genders. The results from this African‐American twin sample are similar to findings among white twin samples.     

Obesity in 70‐Year‐Old Subjects as a Risk Factor for 15‐Year Coronary Heart Disease Incidence

Objective: To investigate the role of obesity in general and waist circumference (WC) and BMI in particular as risk factors for 15‐year incidence of coronary heart disease (CHD) in the elderly. Research Methods and Procedures: This prospective study was based on 1597 (737 males and 860 females) 70‐year‐olds free from CHD and participants of three birth cohorts examined in 1971 to 1972 (Cohort I), 1976 to 1977 (Cohort II), and 1981 to 1982 (Cohort III) at Göteborg, Sweden. Fifteen‐year incidence of CHD (fatal and nonfatal) was ascertained from follow‐up examinations and registers. Relative risk (RR) for first ever CHD in reference to the lowest quartiles of WC and BMI was calculated from Cox regression. Results: In males, RRs for CHD in the highest WC and BMI quartiles were 1.36 [95% confidence interval (CI) 1.00 to 1.85] and 1.42 (95% CI 1.04 to 1.92), respectively, after adjustment for cohorts, smoking habits, diabetes, systolic blood pressure, and total cholesterol. In men, the risk associated with WC was independent of BMI. Neither WC nor BMI was related to CHD risk in females. After exclusion of first 5‐year all‐cause deaths, the adjusted RRs in the highest WC and BMI quartiles in males were 1.47 (95% CI 1.06 to 2.04) and 1.42 (1.04 to 1.92), respectively. In females, a significantly higher RR of 1.41 (95% CI 1.02 to 1.94) was observed in the second BMI quartile only after such exclusions. Discussion: WC, an indicator of both central and general obesity, appears to be a stronger predictor of CHD than BMI in elderly males, but in females, obesity was not a risk factor for CHD.     

Usefulness of Anthropometry and DXA in Predicting Intra‐abdominal Fat in Obese Men and Women

Objective: To investigate the usefulness of anthropometry and DXA in predicting intra‐abdominal fat (IAF) in obese men and women. Research Methods and Procedures: Observational, cross sectional study of 22 women and 18 men with a body mass index of 30 or above. IAF from 20 cm above and 10 cm below the L4 to L5 intervertebral disc was measured by magnetic resonance imaging (MRI) as a reference method. Central abdominal fat was measured from the upper border of L2 to the lower border of L4 by DXA. Waist and hip circumferences were also measured. Results: In obese women DXA, waist circumference and waist‐hip ratio were equally well correlated with IAF (r = 0.74, 0.75, and 0.70, respectively). In obese men DXA was moderately correlated with IAF measured by MRI (r = 0.46), whereas waist circumference and waist‐hip ratio were not significantly correlated with IAF. Discussion: The prediction of IAF in obese subjects was highly dependent on sex more than in non‐obese persons. Anthropometry and DXA were equally useful in obese women, whereas anthropometry had no predictive power and DXA was the only acceptable predictor of IAF in obese men.     

Relationship of Body Composition to Body‐Fatness Estimation in Japanese University Students

Objective: To examine the relationship between self‐estimated whole body size and fatness and whole body and regional composition, and the relationship between self‐estimated whole body fatness and self‐estimated regional fatness in Japanese university students. Research Methods and Procedures: This was a cross‐sectional study using Japanese university students (110 men and 79 women). The percentage of body fat, fat mass (FM), and fat‐free mass (FFM) were measured by underwater weighing and used as body composition variables. Subcutaneous fat thicknesses were determined at seven sites by ultrasonography to estimate regional body composition, and six circumferences and four breadths to estimate regional size. Relative body size and fatness were self‐estimated using a questionnaire. Results: Only women tended to estimate themselves as being fatter than they actually were. Self‐estimated body fatness moderately correlated with the percentage of body fat (men, r = 0.41; women, r = 0.40) FM (men, r = 0.50; women, r = 0.51), and body mass index (r = 0.56 for men and 0.56 for women). After adjusting for the percentages of body fat and FM, self‐estimated fatness correlated with body mass index (r = 0.31 for men and r = 0.37 for women). Among self‐estimated regional fatness, self‐estimated abdominal fatness had the strongest correlation with self‐estimated whole body fatness in both genders. Discussion: The low correlation between estimated and actual body fatness in both genders indicates that Japanese university students, especially women, inaccurately estimate their percentage of body fat. In fact, both men and women primarily estimate their whole body fatness by body weight relative to height.     

Cost‐Effectiveness of a Low‐Carbohydrate Diet and a Standard Diet in Severe Obesity

Objective: Low‐carbohydrate diets have become a popular alternative to standard diets for weight loss. Our aim was to compare the cost‐effectiveness of these two diets. Research Methods and Procedures: The patient population included 129 severely obese subjects (BMI = 42.9) from a randomized trial; participants had a high prevalence of diabetes or metabolic syndrome. We compared within‐trial costs, quality‐adjusted life years (QALYs), and the incremental cost‐effectiveness ratio (CER) for the two study groups. We imputed missing values for QALYs. The CER was bootstrapped to derive 95% confidence intervals and to define acceptability cut‐offs. We took a societal perspective for our analysis. Results: Total costs during the one year of the trial were $6742 ± 6675 and $6249 ± 5100 for the low‐carbohydrate and standard groups, respectively (p = 0.78). Participants experienced 0.64 ± 0.02 and 0.61 ± 0.02 QALYs during the one year of the study, respectively (p = 0.17 for difference). The point estimate of the incremental CER was $?1225/QALY (i.e., the low‐carbohydrate diet dominated the standard diet). However, in the bootstrap analysis, the wide spread of CERs caused the 95% confidence interval to be undefined. The probabilities that the low‐carbohydrate diet was acceptable, using cut‐offs of $50, 000/QALY, $100, 000/QALY, and $150, 000/QALY, were 72.4% 78.6%, and 79.8%, respectively. Discussion: The low‐carbohydrate diet was not more cost‐effective for weight loss than the standard diet in the patient population studied. Larger studies are needed to better assess the cost‐effectiveness of dietary therapies for weight loss.     

Defining Health‐Related Obesity in Prepubertal Children

Objective: The purpose of this study was to develop percentage of fat and waist circumference cut‐points in prepubertal children with the intention of defining obesity associated with cardiovascular disease (CVD) risk. Research Methods and Procedures: A cross‐sectional analysis of 87 prepubertal children aged 4 to 11 years was used. Percentage of body fat was determined by DXA. Waist circumference was measured to the nearest millimeter. Receiver Operating Characteristic analyses of percentage of fat and waist circumference were used to develop cut‐points for individuals with adverse levels of CVD risk factors. Results: The risk factors selected for analyses (i.e., fasting insulin, high‐density lipoprotein cholesterol, low‐density lipoprotein cholesterol, triglycerides, and total cholesterol/high‐density lipoprotein cholesterol) were significantly related to percentage of body fat and waist circumference. Likelihood ratios were used to identify percentage of fat and waist circumference cut‐points associated with adverse cardiovascular risk profiles. Two cut‐points, an upper cut‐point of 33% body fat and a lower cut‐point of 20% body fat, were derived. Waist circumference cut‐points indicative of adverse and normal risk‐factor profiles were 71 cm and 61 cm, respectively. Discussion: The data indicate that children with ≥33% body fat and children with a waist circumference ≥71 cm were more likely to possess an adverse CVD risk‐factor profile than a normal risk‐factor profile. The likelihood of children with <20% body fat or a waist circumference <61 cm possessing an adverse CVD risk‐factor profile as opposed to a normal risk‐factor profile was small. The cut‐points describe an adequate health‐related definition of childhood obesity.     

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.     

Normal Distribution of Body Weight Gain in Male Sprague‐Dawley Rats Fed a High‐Energy Diet

Objective: To investigate the effect of a high‐energy (HE) diet on caloric intake, body weight, and related parameters in outbred male Sprague‐Dawley (SD) rats. Research Methods and Procedures: Twenty‐eight SD rats were fed either chow (C) for 19 weeks or HE diet for 14 weeks and then C for 5 weeks. Blood hormones and metabolites were assayed, and expression of uncoupling protein‐1 and hypothalamic energy‐balance‐related genes were determined by Northern blotting and in situ hybridization, respectively. Results: HE rats gained body weight more rapidly than C animals with a range of weight gains, but there was no evidence that weight gain was bimodally distributed. Caloric intake was transiently elevated after introduction of the HE diet. Transfer of HE rats back to C resulted in a drop in caloric intake, but a stable body weight. In terminal analysis, two of four dissected adipose tissue depots were heavier in rats that had previously been fed HE diet. Blood leptin, insulin, glucose, and nonesterified fatty acids were not different between the groups. Uncoupling protein‐1 mRNA was elevated in interscapular brown adipose tissue from HE rats. There was a trend for agouti‐related peptide mRNA in the hypothalamic arcuate nucleus to be higher in HE rats. Discussion: Contrary to other studies of the SD rat on HE diet, body weight and other measured parameters were normally distributed. There was no segregation into two distinct populations on the basis of susceptibility to diet‐induced obesity. This characteristic may be dependent on the breeding colony from which animals were sourced.     

Carbohydrate—Fat Interactions and Obesity Examined by a Two‐Compartment Computer Model

Objective: A systems dynamics computer model was developed to examine how the interactions between carbohydrate and fat metabolism influence body weight regulation. It reflects the operation of a two reservoir‐system: one representing the body's limited glycogen, and the other, its large fat reserves. The outflows from the reservoirs correspond to the oxidation of glucose and fat, whose relative contributions are affected by the size of the prevailing glycogen and fat reserves. Together, they meet the body's energy expenditure. Replenishments occur three times per day, in portions restoring total glycogen content to specific levels. A parameter mimicking the action of insulin is necessary to create realistic responses. Research Methods and Procedures: The model was run for 125‐day periods to establish the degree of adiposity for which rates of fat oxidation become commensurate with fat intake and the influence thereon of various dietary, environmental, lifestyle, and inherited variables. Results: Equivalent degrees of adiposity can be sustained under a variety of conditions. For instance, the impact on steady‐state body fat contents of a 10% increase or decrease in the energy provided by dietary fat is offset by a 26‐gram decrease or increase in mean glycogen levels. Discussion: Environmental factors such as food diversity, palatability, and availability can be expected to raise the range within which glycogen levels are habitually maintained. This restrains fat oxidation, until expansion of the fat mass is sufficient to promote fat oxidation to a rate commensurate with dietary fat intake. This metabolic leverage can explain why increased food offerings tend to raise the prevalence of obesity.     

Effect of Smoking on the Paradox of High Waist‐to‐Hip Ratio and Low Body Mass Index

Objective: Research on diabetes mellitus (DM) indicates that people with a low body mass index (BMI) but a high waist‐to‐hip ratio (WHR) are in a particularly high‐risk group. The purpose of this study was to investigate the prevalence of and the effect of smoking on this paradoxical relationship. Research Methods and Procedures: Our study sample consisted of 3450 men and 4250 women who had participated in the Korean Nationwide Health Examination Survey. We divided the study sample into tertiles (low, medium, and high), according to the level of WHR and of BMI, which yielded nine different combinations. Individuals exhibiting so‐called paradox A had the highest WHR and the lowest BMI. Results: The prevalence of paradox A was 4.7% for men and 3.8% for women. The overall agreement of WHR and BMI groups was poor [for men: κ = 0.31 and 95% confidence interval (CI) = 0.29 to 0.34; for women: κ = 0.39 and 95% CI = 0.37 to 0.42 for women]. The odds ratios for subjects having paradox A were estimated using a logistic regression model after adjusting for age, age², height, education, smoking, use of alcohol, and exercise. The risk for paradox A among current smokers was 2.1‐fold (95% CI, 1.5 to 3.0) higher for men and 2.5‐fold (95% CI, 1.6 to 3.9) higher for women than for nonsmokers, after adjusting for age and covariates. Discussion: Cigarette smoking may increase the risk of paradox A. The findings of this study should be crossvalidated to different populations.     

Waist Circumference as the Best Predictor of Noninsulin Dependent Diabetes Mellitus (NIDDM) Compared to Body Mass Index,Waist/hip Ratio and Other Anthropometric Measurements in Mexican Americans—A 7-Year Prospective Study

Although a number of obesity-related variables are recognized risk factors for NIDDM, few studies have addressed which one is the best predictor. A cohort of 721 Mexican Americans aged 25–64 years who were free of NIDDM at baseline were followed for an average of 7.2 years; 105 new cases of NIDDM were diagnosed. Body weight, body mass index (BMI), waist and hip circumferences, waist/hip ratio (WHR), triceps and subscapular skinfolds were all positively predictive of NIDDM independent of age and sex. There were modest to strong correlations between these anthropometric variables, however, waist circumference was the strongest predictor of NIDDM. The predictive power of a single measurement of waist circumference was at least equal to that of WHR and BMI combined. The risk of NIDDM for those in the highest quartile of waist circumference was 11 times greater than for those in the lowest quartile (95% confidence interval: 4.2–28.8). The waist-NIDDM relation was stronger in subjects with BMI ≤ 27 kg/m² (OR: 6.0 for a 1 SD difference) than in subjects with BMI > 27 kg/m2 (OR: 1.7 for a 1 SD difference). In multivariate analysis, waist circumference was the only significant predictor of NIDDM in models that included other anthropometric variables either separately or simultaneously. WHR and BMI were independent predictors of NIDDM after adjustment for each other, however, their predictive abilities disappeared after adjustment for waist circumference. The data indicate that waist is the best obesity-related predictor of NIDDM. This finding suggests that the distribution of body fat, especially abdominal localization, is a more important determinant than the total amount of body fat of the development of NIDDM in Mexican Americans.     

Waist Circumference,BMI, Smoking,and Mortality in Middle‐Aged Men and Women

Objective: Measurement of waist circumference alone as a proxy of abdominal fat mass has been suggested as a simple clinical alternative to BMI for detecting adults with possible health risks due to obesity. Research Methods and Procedures: From 1993 to 1997, 27, 178 men and 29, 875 women, born in Denmark, 50 to 64 years of age, were recruited in the Danish prospective study Diet, Cancer and Health. By the end of the year 2000, 1465 deaths had occurred. We evaluated the relationship between waist circumference and BMI (simultaneously included in the model) and all‐cause mortality. We used Cox regression models to estimate the mortality‐rate ratios and to consider possible confounding from smoking. Results: Waist circumference among both men and women showed a strong dose‐response type of relationship with mortality when adjusted for BMI, whereas the low range of BMI was inversely associated with mortality when adjusted for waist circumference. A 10% larger waist circumference corresponded to a 1.48 (95% confidence interval: 1.36 to 1.61) times higher mortality over the whole range of waist circumference. The associations were independent of age and time since baseline examination. Restriction to never smokers showed a similar pattern, but a weakening of the associations. Discussion: Despite the high correlation between waist circumference and BMI, the combination may be very relevant in clinical practice because waist circumference for given BMI was a strong predictor of all‐cause mortality. The inverse association between BMI and mortality for given waist circumference was diminished in never smokers, particularly for high values of BMI.     

Body size and extinction risk in Australian mammals: An information‐theoretic approach

The critical weight range (CWR) hypothesis for Australian mammals states that extinctions and declines have been concentrated in species with body mass between 35 g and 5.5 kg. The biological basis for this hypothesis is that species of intermediate size are disproportionately impacted by introduced predators. The CWR hypothesis has received support from several statistical studies over the past decade, although the evidence is weaker or non‐existent for certain groups such as mesic‐zone mammals and arboreal mammals. In this study, we employ an information‐theoretic model selection approach to gain further insights into the relationship between body mass and extinction risk in Australian mammals. We find evidence, consistent with the CWR hypothesis, that extinction risk peaks at intermediate body masses for marsupials, rodents and ground‐dwelling species, but not for arboreal species. In contrast to previous studies, we find that the CWR describes extinction patterns in the mesic zone as well as the arid zone. In the mesic zone, there is also a weaker tendency for large species above the CWR to be more vulnerable, consistent with extinction patterns on other continents. We find that a more biological plausible Gaussian distribution consistently fits the data better than the polynomial models that have been used in previous studies. Our results justify conservation programmes targeted at species within the CWR across Australia.