The Influence of Anatomical Boundaries,Age, and Sex on the Assessment of Abdominal Visceral Fat

CLASEY, JODY L, CLAUDE BOUCHARD, LAURIE WIDEMAN, JILL KANALEY, C DAVID TEATES, MICHAEL O THORNER, MARK L HARTMAN, ARTHUR WELTMAN. The influence of anatomical boundaries, age, and sex on the assessment of abdominal visceral fat. Single-slice abdominal computed tomography (CT) scanning has been used extensively for the measurement of abdominal visceral fat (AYF). Optimal anatomical scan location and pixel density ranges have been proposed and are specifically reported to allow for the replication and standardization of AVF measurements. Standardization of the anatomical boundaries for CT measurement of AVF and the influence of age and gender on results obtained with different boundary locations have received much less attention. To determine the influence of three boundary analysis methods (AVF-1, AVF-2, and AVF-3) on the measurement of AVF by CT, 54 older (60 years to 79 years) and 37 younger (20 years to 29 years) healthy men and women were examined. The measurement boundary for AVF-1 was the internal most aspect of the abdominal and oblique muscle walls, and the posterior aspect of the vertebral body. AVF-2 used fat measurements enclosed in a boundary formed by the midpoint of the abdominal and oblique muscle walls, and the most posterior aspect of the spinous process. AVF-3 used fat measurements enclosed in a boundary formed by the external border of the abdominal and oblique muscle walls, and the external border of the erector spinae. Greater AVF measures were obtained with AVF-2 and AVF-3 compared with AVF-1 (p<0.0001). These differences were greater in older compared with younger subjects (p<0.0001) and greater in women compared with men (p<0.02). The significantly greater AVF measurements obtained with AVF-2 and AVF-3 resulted from the inclusion of larger amounts of fat that are not drained by the portal circulation. This included retroperitoneal, intermuscular, and intramuscular lipid droplets, which increase with aging. On the basis of these results, we recommend the AVF-1 anatomical boundaries for the measurement of AVF in clinical investigations, particularly with older subjects. These data demonstrate the importance of precise and reproducible anatomical boundaries for the measurement of AVF, particularly in longitudinal studies.     

Visceral Adipose Tissue in Women: Longitudinal Study of the Effects of Fat Gain,Time, and Race

Objective: To determine the effects of fat gain, time, and race on the accumulation of visceral adipose tissue (VAT) in a group of normal‐weight premenopausal women. Research Methods and Procedures: Sixty‐five women participated in the study (32 African American and 33 white). The mean age of subjects was 34 ± 6 years (range, 22 to 47 years). Eligible subjects were women who had body mass indices <25 kg/m² at baseline and who had completed evaluations at baseline and at follow‐up year 1, without intervention. A subset of subjects was reevaluated annually for up to 4 years. Body composition was assessed by DXA, and VAT was determined from a single computed tomography scan. A linear mixed model was used to examine changes in VAT over time, with total body fat as a covariate Results: Total fat mass was not significantly different between races at baseline and increased significantly in both groups over time (p < 0.001). Time‐related increases in total body fat were greater in African‐American women (p < 0.01). VAT was significantly higher in white women at baseline (p < 0.01) and increased significantly over time in both races (p < 0.01), but remained higher in white women (p < 0.001). Increases in VAT, relative to total body fat, were greater than the increases in total body fat over time, independent of age and race (p < 0.001). Discussion: Gaining total body‐fat mass results in a higher increase in VAT, relative to total body fat, regardless of race and age, although African‐American women maintain a lower VAT levels across time.     

Effect of Regain of Body Weight on Regional Body Fat Distribution: Comparison Between Pre- and Postmenopausal Obese Women

The aim of our study was to determine if regain of body weight increases visceral fat in obese women and if regain of weight has a different effect upon pre- and postmenopausal women. Twenty obese women (11 pre- and 9 postmenopausal) underwent a very low energy diet (VLED) for 2 weeks to lose weight. They then regained body weight in spite of the recommended hypocaloric diet. No significant modifications in body fat distribution indexes were found by computed tomography between VLED and after regain of weight. No significant changes were found in metabolic variables. No interactions between menopausal status and regain of body weight were observed. In conclusion, regain of weight does not seem to cause an increase in visceral fat; both pre- and postmenopausal women showed the same body fat distribution before weight loss and after regain of weight.     

Preventing Overestimation of Pixels in Computed Tomography Assessment of Visceral Fat

Objective: Computed tomography (CT) is a common research procedure for measuring abdominal fat distribution, but little is written about the software used to analyze images. Our objective was to compare in‐house and commercially available software for quantitative measurement of abdominal fat distribution. In the process, we encountered some unexpected problems. Research Methods and Procedures: A total of 123 volunteers had single‐slice abdominal CT images taken that were used to evaluate various aspects of the commercial image analysis program. Results: The agreement between the commercial and in‐house programs was excellent (r = 0.996, p < 0.00, 001) for both total and intraabdominal fat, and we were able to reduce between‐observer variability in measured fat areas through the use of statistical handling of region of interest information. We also noted that intracolonic contents sometimes had the same Hounsfield units as adipose tissue. We analyzed single‐slice CT images from 50 volunteers to determine the potential impact of this effect on visceral fat area; the overestimate of visceral fat area was 19 ± 22% (maximum, 112% overestimate). The commercial program could prevent this error, whereas our in‐house program could not. Discussion: We concluded that a readily available commercial image analysis program compares well with a previously validated in‐house program and that it offers some advantages with respect to preventing overestimation of pixels as visceral fat.     

Relationship among Habitual Tea Consumption,Percent Body Fat,and Body Fat Distribution

Objective: To disclose the possible relationship between habitual tea consumption and changes in total body fat and fat distribution in humans. Research Methods and Procedures: A cross‐sectional survey of 1210 epidemiologically sampled adults (569 men and 641 women) were enrolled in our study. Tea consumption and other lifestyle characteristics were obtained by structured questionnaires. Percent body fat (BF%) was measured using bioelectrical impedance analysis. Body fat distribution was assessed using waist‐to‐hip ratio (WHR). Results: Among the 1103 analyzed subjects, 473 adults (42.9%) consumed tea once or more per week for at least 6 months. The habitual tea drinkers were male‐dominant, more frequently current smokers, and alcohol or coffee drinkers than the nonhabitual tea drinkers. Habitual tea drinkers for more than 10 years showed a 19.6% reduction in BF% and a 2.1% reduction in WHR compared with nonhabitual tea drinkers. The multiple stepwise regression models revealed that men, older age, higher BMI, and current smokers were positive factors for BF% and WHR. In contrast, longer duration of habitual tea consumption and higher total physical activity were negative factors for BF%. Longer duration of habitual tea consumption, higher socioeconomic status, and premenopausal status were negative factors for WHR. Discussion: An inverse relationship may exist among habitual tea consumption, BF%, and body fat distribution, especially for subjects who have maintained the habit of tea consumption for more than 10 years.     

The Use of Anthropometric and Dual-Energy X-ray Absorptiometry (DXA) Measures to Estimate Total Abdominal and Abdominal Visceral Fat in Men and Women

CLASEY, JODY L., CLAUDE BOUCHARD, C. DAVID TEATES, JILL E. RIBLETT, MICHAEL O. THORNER, MARK L. HARTMAN, AND ARTHUR WELTMAN. the use of anthropometric and dual-energy X-ray absorptiometry (DXA) measures to estimate total abdominal and abdominal visceral fat in men and women. Obes Res. Objective: A single-slice computed tomography (CT) scan provides a criterion measure of total abdominal fat (TAF) and abdominal visceral fat (AVF), but this procedure is often prohibitive due to radiation exposure, cost, and accessibility. In the present study, the utility of anthropometric measures and estimates of trunk and abdominal fat mass by dual-energy X-ray absorptiometry (DXA) to predict CT measures of TAF and AVF (cross-sectional area, cm²) was assessed. Research Methods and Procedures: CT measures of abdominal fat (at the level of the L4-L5 inter-vertebral space), DXA scans, and anthropometric measures were obtained in 76 Caucasian adults ages 20–80 years. Results: Results demonstrated that abdominal sagittal diameter measured by anthropometry is an excellent predictor of sagittal diameter measured from a CT image (r = 0. 88 and 0. 94; Total Error [TE]=4. 1 and 3. 1 cm, for men and women, respectively). In both men and women, waist circumference and abdominal sagittal diameter were the anthropometric measures most strongly associated with TAF (r = 0. 87 to 0. 93; Standard Error of Estimate (SEE) = 60. 7 to 75. 4 cm²) and AVF (r = 0. 84 to 0. 93; SEE = 0. 7 to 30. 0 cm²). The least predictive anthropometric measure of TAF or AVF was the commonly used waist-to-hip ratio (WHR). DXA estimates of trunk and abdominal fat mass were strongly associated with TAF (r =. 94 to 0. 97; SEE = 36. 9 to 50. 9 cm²) and AVF (r = 0. 86 to 0. 90; SEE = 4. 9 to 27. 7 cm²). Discussion: The present results suggest that waist circumference and/or abdominal sagittal diameter are better predictors of TAF and AVF than the more commonly used WHR. DXA trunk fat and abdominal fat appear to be slightly better predictors of TAF but not AVF compared to these anthropometric measures. Thus DXA does not offer a significant advantage over anthropometry for estimation of AVF.     

Ethnic Differences in Visceral Adipose Tissue and Type 2 Diabetes: Filipino,African‐American,and White Women

Objective: To compare ethnic differences in visceral adipose tissue (VAT), assessed by computed tomography, and type 2 diabetes risk among 55‐ to 80‐year‐old Filipino, African‐American, and white women without known cardiovascular disease. Research Methods and Procedures: Subjects were participants in the Rancho Bernardo Study (n = 196), the Filipino Women's Health Study (n = 181), and the Health Assessment Study of African‐American Women (n = 193). Glucose and anthropometric measurements were assessed between 1995 and 2002. Results: African‐American women had significantly higher age‐adjusted BMI (29.7 kg/m²) and waist girth (88.1 cm) compared with Filipino (BMI, 25.5 kg/m²; waist girth, 81.9 cm) or white (BMI: 26.0 kg/m²; waist girth: 80.7 cm) women. However, VAT was significantly higher among Filipino (69.1 cm³) compared with white (62.3 cm³; p = 0.037) or African‐American (57.5 cm³, p < 0.001) women. VAT correlated better with BMI (r = 0.69) and waist (r = 0.77) in whites, compared with Filipino (r = 0.42; r = 0.59) or African‐American (r = 0.50; r = 0.56) women. Age‐adjusted type 2 diabetes prevalence was significantly higher in Filipinas (32.1%) than in white (5.8%) or African‐American (12.1%) women. Filipinas had higher type 2 diabetes risk compared with African Americans [adjusted odds ratio, 2.30; 95% confidence interval (CI), 1.09 to 4.86] or whites (adjusted odds ratio, 7.51; 95% CI, 2.51 to 22.5) after adjusting for age, VAT, exercise, education, and alcohol intake. Discussion: VAT was highest among Filipinas despite similar BMI and waist circumference as whites. BMI and waist circumference were weaker estimates of VAT in Filipino and African‐American women than in whites. Type 2 diabetes prevalence was highest among Filipino women at every level of VAT, but VAT did not explain their elevated type 2 diabetes risk.     

Abdominal Visceral Fat is Associated with a BclI Restriction Fragment Length Polymorphism at the Glucocorticoid Receptor Gene Locus

Several investigations have suggested that body fat distribution is influenced by nonpathologic variations in the responsiveness to Cortisol. Genetic variations in the glucocorticoid receptor (GRL) could therefore potentially have an impact on the level of abdominal fat. A restriction fragment length polymorphism (RFLP) has previously been detected with the BelI restriction enzyme in the GRL gene identifying two alleles with fragment lengths of 4.5 and 2.3 kb. This study investigates whether abdominal fat areas measured by computerized tomography (CT) are associated with this polymorphism in 152 middle-aged men and women. The less frequent 4.5-kb allele was found to be associated with a higher abdominal visceral fat (A VF) area independently of total body fat mass (4.5/4.5 vs. 2.3/2.3 kb genotype; men: 190.7 ± 30.1 vs. 150.7 ± 33.3 cm², p=0.04; women: 132.7 ± 37.3 vs. 101.3 ± 34.5 cm², p=0.06). However, the association with AVF was seen only in subjects of the lower tertile of the percent body fat level. In these subjects, the polymorphism was found to account for 41% (p=0.003) and 35% (p=0.007), in men and women, respectively, of the total variance in AVF area. The consistent association between the GRL polymorphism detected with BelI and AVF area suggests that this gene or a locus in linkage disequilibrium with the BelI restriction site may contribute to the accumulation of AVF.     

Evidence of linkage and association with body fatness and abdominal fat on chromosome 15q26

Objective: In the present study, we undertook a two‐step fine mapping of a 20‐megabase region around a quantitative trait locus previously reported on chromosome 15q26 for abdominal subcutaneous fat (ASF) in an extended sample of 707 subjects from 202 families from the Quebec Family Study. Research Methods and Procedure: First, 19 microsatellites (in addition to the 7 markers initially available on 15q24‐q26; total = 26) were genotyped and tested for linkage with abdominal total fat, abdominal visceral fat, and ASF assessed by computed tomography and with fat mass (FM) using variance component‐based approach on age‐ and sex‐adjusted phenotypes. Second, 16 single nucleotide polymorphisms (SNPs) were genotyped and tested for association using family‐based association tests. Results: After the fine mapping, the peak logarithm of odds ratio (LOD) score (marker D15S1004) increased from 2.79 to 3.26 for ASF and from 3.52 to 4.48 for FM, whereas for abdominal total fat, the peak linkage (marker D15S996) decreased from 2.22 to 1.53. No evidence of linkage was found for abdominal visceral fat. Overall, for genotyped SNPs, three variants located in the putative MCTP2 gene were significantly associated with FM and the three abdominal fat phenotypes (p ≤ 0.05). The major allele and genotype of rs1424695 were associated with higher adiposity values (p < 0.004). The same trend was found for the two other polymorphisms (p < 0.05). None of the other SNPs was associated with adiposity phenotypes. The linkage for FM became non‐significant (LOD = 0.84) after adjustment for the MCTP2 polymorphisms, whereas the one for ASF remained unchanged. Discussion: These results suggest that the MCTP2 gene, located on chromosome 15q26, influences adiposity. Other studies will be needed to investigate the function of the MCTP2 gene and its role in obesity.     

Influence of Total vs. Visceral Fat on Insulin Action and Secretion in African American and White Children

Objective: To examine whether total body fat (FAT) in general or visceral fat (VFAT) in particular is associated with greater metabolic risk in white and African American children. Research Methods and Procedures: A total of 68 white and 51 African American children had measures of insulin sensitivity (Si) and acute insulin response (AIR) by a frequently sampled intravenous glucose tolerance test, total body fat by DXA and abdominal fat distribution (visceral vs. subcutaneous) by computed tomography. The influence of FAT and VFAT on insulin parameters were examined by comparing subgroups of children with high or low FAT vs. high or low VFAT and by multiple regression analysis. Results: In whites, fasting insulin, Si, and AIR were significantly influenced by FAT, but not VFAT (e.g., for Si, 9.8 ± 0.8 in low FAT vs. 4.6 ± 0.7 × 10^?4/min/[μIU/mL] in high FAT, p < 0.05; 6.8 ± 0.7 in low VFAT vs. 7.5 ± 0.8 × 10^?4/min/[μIU/mL] in high VFAT, p > 0.1). In African Americans, fasting insulin and Si were also primarily influenced by FAT (e.g., for Si, 4.9 ± 0.4 in low FAT vs. 2.8 ± 0.5 × 10^?4/min/[μIU/mL] in high FAT, p < 0.05) but not by VFAT, and there were no significant effects of either fat compartment on AIR. In multiple regression analysis, Si was significantly influenced by FAT (negative effect), ethnicity (lower in African Americans), and gender (lower in females), whereas fasting insulin was significantly influenced by VFAT (positive effect), ethnicity (higher in African Americans), and fat free mass (positive effect). Discussion: Body fat in general is the predominant factor influencing Si, but VFAT may have additional effects on fasting insulin. The lack of major effects of VFAT on Si in children may be explained by lower levels of VFAT or because VFAT affects aspects of whole body insulin action that are not measured by the minimal model.     

Increased Energy Metabolism and Suppressed Body Fat Accumulation in Mice by a Low Concentration of Conjugated Linoleic Acid

We investigated the dose-effect of the long-term intake of conjugated linoleic acid (CLA) on the energy metabolism and fat accumulation in mice. Five-week-old male Std ddY mice were fed on a diet containing none (control), 0.25%, 0.5% or 1.0% CLA for 4 or 8 weeks. The body weight was lower in the CLA groups than in the control group, and significant differences were detected between the 1.0% CLA group and the control group at both 4 and 8 weeks. The epididymal and perirenal adipose tissue weights were significantly lower in the CLA groups than in the control group. The liver weight and hepatic triglyceride values were higher in the 1.0% CLA group than in the other groups. The metabolic rate was measured after 8 weeks by using a gas analyzer. The oxygen consumption of the mice in the CLA groups was significantly higher than that of the control mice. Since there was a significant effect on the mice supplemented with 0.25% CLA, low concentration of CLA is suggested to suppress the body fat accumulation and increase the energy metabolism.     

Daily Oral Oleoyl‐Estrone Gavage Induces a Dose‐Dependent Loss of Fat in Wistar Rats

Objective: To establish whether single daily oral doses of oleoyl‐estrone result in dose‐dependent slimming effects on normal weight rats, and to determine the changes in energy parameters induced by this treatment. Research Methods and Procedures: The effects of a daily oral gavage of oleoyl‐estrone (0, 0.2, 0.5, 1, 2, 5, 10, and 20 μmol/kg per day) in 0.2 ml of sunflower oil given over a 10‐day period were studied in groups, each of which contained six adult female Wistar rats initially weighing 190 to 230 g. A group of intact control rats receiving no gavage was included for comparison. Body weight and food intake were measured daily. Rats were killed on day 10 of treatment, and body composition (protein nitrogen, lipids, and water), liver lipids, and plasma parameters (glucose, triacylglycerols, total cholesterol, free fatty acids, 3‐hydroxybutyrate, urea, aspartate, alanine transaminases, insulin, leptin, and free and acyl‐estrone) were measured. Results: The administration of oleoyl‐estrone resulted in a dose‐dependent loss of body fat, because of a partly maintained energy expenditure combined with decreased food intake. The differences in the energy budget were met by internal fat pools. The changes recorded did not affect the levels of the main plasma energy homeostasis indicators: unaltered glucose, triacylglycerols, free fatty acids, 3hydroxybutyrate, and urea. Protein was accrued even under conditions of severe lipid store drainage. There were no changes in transaminases. No lipid accumulation was recorded in the liver. Plasma insulin and leptin levels decreased with increased oleoyl‐estrone doses, whereas the levels of free and esterified estrone increased with treatment, although not in proportion to the dose received. Discussion: Oral treatment with oleoyl‐estrone resulted in the specific dose‐related loss of fat reserves with little change to other metabolic parameters. These results agree with the postulated role of oleoyl‐estrone as a ponderostat signal.     

Alcohol as a Risk Factor for Cancer Burden: A Review

Alcohol is eliminated from the body by various metabolic mechanisms. The primary enzymes in such mechanism involved are alcohol dehydrogenase, aldehyde dehydrogenase, cytochrome P450 2E1, and catalase. Variations in the genes for these enzymes have been found to influence alcohol consumption. The consequences of alcohol metabolism include oxygen deficits (i.e., hypoxia) in the liver, resulting in the formation of harmful compounds (i.e., adducts) and highly reactive oxygen-containing molecules (i.e., reactive oxygen species) that can damage cell components. Approximately, worldwide 3.6 % of cancers derive from chronic alcohol drinking, including those of the upper aerodigestive tract, the liver, the colorectum and the breast. Although the mechanisms for alcohol-associated carcinogenesis are not completely understood, recent findings have focused on acetaldehyde, the first and most toxic ethanol metabolite, as a cancer-causing agent. Alcohol-related carcinogenesis may aggravate due to other factors such as smoking and being triggered by genetic susceptibility. Besides, the role of genetic polymorphisms of the alcohol-metabolizing enzymes could not be ruled out.     

Fat and energy partitioning: longitudinal observations in leptin-treated adults homozygous for a Lep mutation

Objective: Partitioning of body energy content in the aleptinemic ob/ob mouse differs from that in wild‐type mice, but it is not known whether parallel differences exist between humans with leptin (Lep) gene mutations and healthy adults. The objective of this study was to evaluate body composition in three leptin‐treated Turkish adults homozygous for a missense mutation (C→T substitution at codon 105 resulting in Arg→Trp) of Lep. Research Methods and Procedures: Subjects, one male and two female Turkish family members, were evaluated at baseline and treated for 18 months with r‐MetHuLeptin. Patient data (fat mass, energy content) were compared with adult sex‐specific predicted values (adjusted for weight, height, and age) derived in healthy control subjects. Results: Weight loss with leptin treatment was substantial, ranging from 43.9% to 52.1%. At baseline and with leptin treatment, the two women had a fat mass and energy content similar (±12%) to predicted values. Baseline fat and energy content in the male patient was high compared with predicted values (e.g., fat +33%) but approached and reached normal values (e.g., fat, +2%) after 18 months of leptin therapy. Discussion: Adult women with Lep mutations had body composition similar to normal women at baseline and with leptin treatment. In contrast, the man with a Lep mutation had high body fat in the untreated state but a normal male phenotype with leptin administration, possibly secondary to androgenic fat partitioning effects. Fat and energy partitioning can, thus, be quantitatively assessed and linked with potential hormonal mechanisms in humans with inherited disturbances in energy regulation.     

Visceral Leishmaniasis and Immunocompromise as a Risk Factor for the Development of Visceral Leishmaniasis: A Changing Pattern at The Hospital for Tropical Diseases,London

Visceral leishmaniasis (VL) is a parasitic protozoon infection caused by the Leishmania species and transmitted by sandflies. Patients acquire VL in five main tropical areas and the Mediterranean basin, and clinicians from non-endemic regions regularly see infected patients. We describe the population presenting with VL to the Hospital for Tropical Diseases (HTD), London and identify risk factors for developing VL.

Methods and Principal Findings

A retrospective study of imported VL to the HTD, London including patients diagnosed and/or managed at the HTD between January 1995 and July 2013. We analyse patient demographics, risk factors for developing VL, diagnosis, investigation, management and outcome. Twenty-eight patients were treated for VL at the HTD over an 18 year period. The median age at VL diagnosis was 44 years (range 4–87 years) with a male to female ratio of 2:1. Most patients were British and acquired their infection in the Mediterranean basin. The median time from first symptom to diagnosis was six months with a range of 1–12 months and diagnosis included microscopic visualisation of leishmania amastigotes, positive serological tests (DAT and k39 antibody) or identification of leishmania DNA. Nineteen patients had some form of immunocompromise and this has increased proportionally compared to previously described data. Within the immunocompromised group, the ratio of those with autoimmune disease has increased. Immunocompromised patients had lower cure and higher relapse rates.

Conclusions

The rise of VL in patients with immunocompromise secondary to autoimmune disease on immunomodulatory drugs presents new diagnostic and therapeutic challenges. VL should be a differential diagnosis in immunocompromised patients with pyrexia of unknown origin returning from travel in leishmania endemic areas.     

Waist Circumference as a Screening Tool for Cardiovascular Risk Factors: Evaluation of Receiver Operating Characteristics (ROC)

To evaluate the receiver operating characteristics (ROC) to determine the cutoffs of waist circumference as a potential population directed screening tool for hypercholesterolaemia (≥6.5 mmol/L), low high density lipoprotein cholesterol (<0.9 mmol/L), and hypertension (treated and/or systolic ≥160 and/or diastolic blood pressure ≥95 mmHg), in 2183 men and 2698 women aged 20 to 59 years selected at random from Dutch civil registries. Main outcome measures: Height, weight, body mass index (BMI), waist circumference, total plasma cholesterol and high density lipoprotein cholesterol concentrations, and blood pressure. Results: ROC curves showed that sensitivity equalled specificity at waist circumferences between 93–95 cm in men and 81–84 cm in women for identifying individual risk factors, and 92 cm in men and 81 cm in women for identifying those with at least one risk factor. Sensitivity and specificity were equal at levels between 61% to 69% for identifying individual risk factors, with positive predictions (56.8% in men and 37.8% in women) within 2% of those using previously defined ‘Action Level 1’ of waist circumference 94 cm in men and 80 cm in women (58.8% in men and 37.4% in women). Risk prediction by anthropometric methods was relatively low: ROC areas for identifying each risk factor by waist varied from 55% to 60%, and reached about 65% for identifying at least one risk factor. Height accounted for less than 03% of variance in waist circumference. Using BMI at 25 kg/m² gave similar prediction to waist, but its combination with waist did not improve predictive values. Conclusions: Measurement of waist circumference ‘Action Level 1’ at 94 cm (37 inches) in men and 80 cm (32 inches) in women could be adopted as a simpler valid alternative to BMI for health promotion, to alert those at risk of cardiovascular disease, and as a guide to risk avoidance by self-weight management     

Genetic Studies of Spectrin in the Larval Fat Body of Drosophila melanogaster: Evidence for a Novel Lipid Uptake Apparatus

Spectrin cytoskeleton defects produce a host of phenotypes affecting the plasma membrane, cell polarity, and secretory membrane traffic. However, many of the underlying molecular mechanisms remain unexplained by prevailing models. Here we used the larval fat body of Drosophila melanogaster as a genetic model system to further elucidate mechanisms of αβ-spectrin function. The results provide unexpected new insights into spectrin function as well as mechanisms of dietary fat uptake and storage. We show that loss of α- or β-spectrin in the fat body eliminated a population of small cortical lipid droplets and altered plasma membrane architecture, but did not affect viability of the organism. We present a novel model in which αβ-spectrin directly couples lipid uptake at the plasma membrane to lipid droplet growth in the cytoplasm. In contrast, strong overexpression of β-spectrin caused fat body atrophy and larval lethality. Overexpression of β-spectrin also perturbed transport of dietary fat from the midgut to the fat body. This hypermorphic phenotype appears to be the result of blocking secretion of the lipid carrier lipophorin from fat cells. However, this midgut phenotype was never seen with spectrin loss of function, suggesting that spectrin is not normally required for lipophorin secretion or function. The β-spectrin hypermorphic phenotype was ameliorated by co-overexpression of α-spectrin. Based on the overexpression results here, we propose that β-spectrin family members may be prone to hypermorphic effects (including effects on secretion) if their activity is not properly regulated.