Mechanisms of adipose tissue extracellular matrix alterations in an in vitro model of adipocytes hypoxia and aging.

Fibrosis has been considered as a hallmark of dysfunctional adipose tissue (AT), however the role and mechanisms of fibrosis in the age related AT dysfunction are not yet well characterized. The aim of the study was to investigate the mechanisms of extracellular matrix (ECM) alterations and the role of caveolins, using an in vitro model of adipocyte aging and hypoxia. Hypoxic adipocytes, but also aged adipocytes, were characterized by a significant increase in gene expression of pro-inflammatory cytokines and ECM components. Immunofluorescence analysis confirmed an increase in collagen VI-A3 in hypoxic and also in aged adipocytes. However aged adipocytes were characterized by only a slight increase in HIF1α immunofluorescence and by a more relevant increase in senescence compared to hypoxic and mature adipocytes, with an increase in p-53 protein and a decrease in SIRT 1 protein. Immunofluorescence and western blot analysis revealed a significant decrease in caveolin-1 expression in hypoxic adipocytes and even more in aged adipocytes. In conclusions, aging adipocytes are associated to alteration of ECM and fibrosis, by modulation of the caveolins through complex mechanisms where inflammation, hypoxia and cellular senescence are coexisting.

Role of adipose tissue in melanoma cancer microenvironment and progression.

BACKGROUND: An epidemiological association between excess weight and increased risk of cancer has been described in melanoma, for which the physiopathological mechanisms are still unknown. The study of tumor microenvironment and of the role of adipocytes in cancer development, progression and metastasis has recently received great interest. However, the role of peritumoral adipocytes has been characterized only in a few types of cancer, and in melanoma it still remains to be defined. METHODS: We investigated the interactions between adipocytes and melanoma cells using an in vitro co-culture system. We studied the morphological and functional properties of 3T3-L1 adipocytes before and after co-culture with A375 melanoma cells, in order to assess the role of adipocytes on melanoma migration. RESULTS: Morphological analysis showed that after 6 days of co-culture 3T3-L1 adipocytes were reduced in number and size. Moreover, we observed the appearance of dedifferentiated cells with a fibroblast-like phenotype that were not present in controls and that had lost the expression of some adipocyte-specific genes, and increased the expression of collagen, metalloproteinases and genes typical of dedifferentiation processes. Through the Matrigel Invasion Test, as well the Scratch Test, it was possible to observe that co-culture with adipocytes induced in melanoma cells increased migratory capacity, as compared with controls. In particular, the increase in migration observed in co-culture was suppressed after adding the protein SFRP-5 in the medium, supporting the involvement of the Wnt5a pathway. The activation of this pathway was further characterized by immunofluorescence and western blot analysis, showing in melanocytes in co-culture the activation of ß-catenin and LEF-1, two transcription factors involved in migration processes, neo-angiogenesis and metastasis. CONCLUSIONS: These data allow us to hypothesize a dedifferentiation process of adipocytes toward fibroblast-like cells, which can promote migration of melanoma cells through activation of Wnt5a and the intracellular pathways of ß-catenin and LEF-1.

Assessing the Risk of Sarcopenia in the Elderly: The Mini Sarcopenia Risk Assessment (MSRA) Questionnaire.

OBJECTIVES: to validate the MSRA questionnaire proposed as prescreening tool for sarcopenia, in a population of community-dwelling elderly subjects. DESIGN: observational study. SETTING: community dwelling elderly subjects. PARTICIPANTS: 274 community dwelling elderly subjects, 177 women and 97 men, aged 66-78 years. MEASUREMENTS: Based on EWGSOP diagnostic criteria subjects were classified as sarcopenic and non-sarcopenic. The Mini Sarcopenia Risk Assessment (MSRA) questionnaire, is composed of seven questions and investigates anamnestic and nutritional characteristics related to risk of sarcopenia onset (age, protein and dairy products consumption, number of meals per day, physical activity level, number of hospitalizations and weight loss in the last year). RESULTS: 33.5% of the study population, were classified as sarcopenic. With the 7-item MSRA score, subjects with a score of 30 or less, had a 4-fold greater risk of being sarcopenic than subjects with a score higher than 30 (OR:4.20;95% CI:2.26-8.06); area under the ROC curve was 0.786 (95% CI:0.725-0.847). In a logistic regression, considering as dependent variable the probability of being sarcopenic, and as independent variables the 7 items of the questionnaire, two items (number of meals and milk and dairy products consumption) showed non-significant diagnostic power. A 5-item score was then derived and the area under the ROC curve was 0.789 (95% IC:0.728-0.851). Taking into account the cost of false positive and false negative costs and the prevalence of sarcopenia, the "optimal" threshold of the original MSRA score (based on 7 items) is 30, with a sensitivity of 0.804 and a specificity of 0.505, while the "optimal" threshold of the MSRA score based on 5 items, is 45, with a sensitivity of 0.804 and a specificity of 0.604. CONCLUSION: this preliminary study shows that the MSRA questionnaire is predictive of sarcopenia and can be suggested as prescreening instrument to detect this condition. The use of a short form of the MSRA questionnaire improves the capacity to identify sarcopenic subjects.

Role of Anti-Inflammatory Cytokines on Muscle Mass and Performance Changes in Elderly Men and Women.

OBJECTIVES: Investigate the presence of a correlation between systemic inflammatory profile of community-dwelling individuals and the loss of muscular mass and performance in old age over a 4.5y follow-up, focusing on the role of anti-inflammatory cytokines in muscular changes in elderly. DESIGN: Longitudinal clinical study. SETTING: Subjects were randomly selected from lists of 11 general practitioners in the city of Verona, Italy. PARTICIPANTS: The study included 120 subjects, 92 women and 28 men aged 72.27±2.06 years and with BMI of 26.52±4.07 kg/m2 at baseline. MEASUREMENTS: Six minutes walking test (6MWT), appendicular and leg fat free mass (FFM) as measured with Dual Energy X-ray absorptiometry, were obtained at baseline and after 4.5 years (4.5y) of mean follow-up. Height, weight, body mass index (BMI), and circulating levels of TNFα, IL-4, IL-10, and IL-13 were evaluated at baseline. RESULTS: A significant reduction of appendicular FFM, leg FFM and 6MWT performance (all p<0.001) was observed after 4.5 y follow-up. In a stepwise regression model, considering appendicular FFM decline as dependent variable, lnIL-4, BMI, baseline appendicular FFM, lnTNFα and lnIL-13 were significant predictors of appendicular FFM decline explaining 30.8% of the variance. While building a stepwise multiple regression considering leg FFM as a dependent variable, lnIL-4, BMI and leg FFM were significant predictors of leg FFM decline and explained 27.4% of variance. When considering 6MWT decline as a dependent variable, baseline 6MWT, lnIL-13 and lnTNFα were significant predictors of 6MWT decline to explain 22.9% of variance. CONCLUSIONS: Our study suggest that higher serum levels of anti-inflammatory markers, and in particular IL-4 and IL-13, may play a protective role on FFM and performance maintenance in elderly subjects.

Inflammation and nutritional status as predictors of physical performance and strength loss during hospitalization.

OBJECTIVES: The aim of this study was to examine changes in physical performance and handgrip strength during hospitalization as well as to evaluate their interrelationship with inflammatory and nutritional status. DESIGN: Data were available on 302 elderly patients with a mean age of 80.83±7.14 years. Handgrip strength, gait speed and chair-stand test were assessed at admission and before discharge. In all subjects, serum CRP values and Mini Nutritional Assessment scores were also evaluated. RESULTS: The risk of worsening in chair-stand test performance was 4.2 (95% confidence interval (CI): 1.574-11.310) for subjects with simultaneous presence of malnutrition and CRP⩾50 and 3.3 mg/dl (95% CI: 1.127-9.423) for subjects with CRP⩾50 mg/l not malnourished in comparison with subjects with Mini Nutritional Assessment (MNA)⩾24 and CRP⩽10 mg/l. The risk of handgrip strength loss was 8.8 (95% CI: 3.545-21.662) in subjects with simultaneous presence of malnutrition and CRP⩾50 and 2.9 mg/dl (95% CI: 1.223-6.783) in subjects with CRP⩾50 mg/l not malnourished in comparison with subjects with MNA⩾24 and CRP⩽10 mg/l. CONCLUSIONS: Simultaneous presence of high CRP values and malnutrition determines an additive effect on muscle strength loss and physical performance.

Lipid droplets characterization in adipocyte differentiated 3T3-L1 cells: size and optical density distribution.

The 3T3-L1 cell line, derived from 3T3 cells, is widely used in biological research on adipose tissue. 3T3-L1 cells have a fibroblast-like morphology, but, under appropriate conditions, they differentiate into an adipocyte-like phenotype. During the differentiation process, 3T3-L1 cells increase the synthesis of triglycerides and acquire the behavior of adipose cells. In particular, triglycerides accumulate in lipid droplets (LDs) embedded in the cytoplasm. The number and the size distribution of the LDs is often correlated with obesity and many other pathologies linked with fat accumulation. The integrated optical density (IOD) of the LDs is related with the amount of triglycerides in the droplets. The aim of this study is the attempt to characterize the size distribution and the IOD of the LDs in 3T3-L1 differentiated cells. The cells were differentiated into adipocytes for 5 days with a standard procedure, stained with Oil Red O and observed with an optical microscope. The diameter, area, optical density of the LDs were measured. We found an asymmetry of the kernel density distribution of the maximum Feret's diameter of the LDs with a tail due to very large LDs. More information regarding the birth of the LDs could help in finding the best mathematical model in order to analyze fat accumulation in adipocytes.

Effect of moderate weight loss on hepatic, pancreatic and visceral lipids in obese subjects.

OBJECTIVE: To compare the effects of weight loss on visceral and subcutaneous abdominal fat, liver and pancreas lipid content and to test the effects of these changes on metabolic improvement observed after weight loss. DESIGN: Weight-loss program designed to achieve a loss of 7-10% of the initial weight. SUBJECTS: 24 obese subjects (13 males and 11 females) with age ranging from 26 to 69 years and body mass index (BMI) 30.2-50.5 kg m(-2). MEASUREMENTS: weight, BMI, waist circumference, body composition as assessed by dual-energy X-ray absorptiometry, metabolic variables, leptin, adiponectin, visceral and subcutaneous abdominal fat, liver and pancreas lipid content as assessed by magnetic resonance were evaluated before and after weight loss achieved by hypocaloric diet. RESULTS: After a mean body weight decrease of 8.9%, BMI, waist circumference, fat mass, all metabolic variables, homeostasis model assessment of insulin resistance (HOMA), alanine amino transferase, gamma glutamyl transpeptidase, high-sensitivity C-reactive protein (hs-CRP) and leptin, but not adiponectin and high-density lipoprotein-cholesterol, significantly decreased (all P<0.01). Visceral and subcutaneos abdominal fat, liver and pancreas lipid content significantly decreased (all P<0.01). Percent changes in liver lipid content were greater (84.1±3%) than those in lipid pancreas content (42.3±29%) and visceral abdominal fat (31.9±15.6%). After weight loss, percentage of subjects with liver steatosis decreased from 75 to 12.5%. Insulin resistance improvement was predicted by changes in liver lipid content independently of changes in visceral fat, pancreas lipid content, systemic inflammation, leptin and gender. CONCLUSION: Moderate weight loss determines significant decline in visceral abdominal fat, lipid content in liver and pancreas. Reduction of liver lipid content was greater than that of pancreas lipid content and visceral fat loss. Liver lipid content is the strongest predictor of insulin resistance improvement after weight loss.

Relation between adiponectin and bone mineral density in elderly post-menopausal women: role of body composition, leptin, insulin resistance, and dehydroepiandrosterone sulfate.

INTRODUCTION: Adipocytokines have been proposed as new mediators of the protective effects of fat mass on the skeleton. The aim of this study was to test the relationship between adiponectin, leptin, and bone mineral density (BMD), independently of body composition, insulin resistance, and other factors known to affect bone metabolism. METHODS: Thirty-six post-menopausal non-diabetic elderly women, with ages ranging from 66 to 77 yr took part in the study. In all subjects we evaluated body weight, height, body mass index (BMI), waist circumference, adiponectin, leptin, insulin, DHEAS, and homeostasis model assessment of insulin resistance (HOMA), as well as yr since menopause. Total body fat mass (FM) and BMD at whole body and femoral level were measured with Dual energy X-ray Absorptiometry (DXA). Volumetric BMD was defined as the ratio between total body BMD and height. RESULTS: Leptin was positively and adiponectin negatively related with whole body and femoral BMD. Positive associations between insulin, HOMA, DHEAS, and BMD measures were also found. After adjusting for FM, only adiponectin maintained a significant relation with whole body and femoral BMD; the strength of this association was reduced after adjustment for insulin resistance, estimated by HOMA. In stepwise multiple linear regression analyses adiponectin explained 11.7% of total BMD variance, 17.4% of femoral neck BMD variance, and 30.7% of volumetric BMD variance, independently of BMI, FM, leptin, HOMA, and DHEAS. CONCLUSIONS: The present study may suggest possible involvement of adiponectin in bone metabolism, independently of FM and insulin resistance even in elderly post-menopausal women.

Weight loss and quality of life improvement in obese subjects treated with sibutramine: a double-blind randomized multicenter study.

BACKGROUND AND AIM: Obesity affects cardiovascular risk and also quality of life (QoL). The aim of this study was to test weight loss and impact on QoL after sibutramine treatment in obese subjects. METHODS: Double-blind randomized trial on 309 outpatients (51 males, 258 females; age 41.8 +/- 10.9 years, BMI 35.0 +/- 3.1 kg/m(2)) randomized to sibutramine (n = 154) or to placebo (n = 155) treatment. A combination of sibutramine 10 mg or matching placebo and a balanced hypocaloric diet was given for 6 months with monthly evaluations. The main outcome measures were weight loss, the impact of weight on QoL, BMI, and waist circumference. RESULTS: The mean weight reduction was 8.2 kg in the sibutramine group and 3.9 in the placebo group at 6 months (p < 0.01). 40% of the sibutramine subjects and 14% of the control subjects lost > or =10% of their body weight (p < 0.01). The improvement in the impact of weight on QoL was statistically significant only in the sibutramine group at 6 months (mean -12.5 vs. -4.5 points; p < 0.01). In the sibutramine group the reduction in BMI (-3.1 vs. -1.4 kg/m(2)) and waist circumference (7.7 vs. 3.5 cm) was significantly greater (p < 0.001). The incidence of adverse events was low and similar to the placebo. CONCLUSIONS: This study confirmed that sibutramine significantly enhances the effect of diet on weight loss, BMI and waist circumference reduction, and showed a significant improvement of QoL.

Adiponectin gene expression and adipocyte NF-kappaB transcriptional activity in elderly overweight and obese women: inter-relationships with fat distribution, hs-CRP, leptin and insulin resistance.

OBJECTIVE: The regulatory processes that modulate adiponectin production and the mechanisms involved in nuclear factor kB (NF-kB) transcriptional activity in human adipocytes are not yet fully known. The aim of our study was to evaluate the inter-relationships between body fat, fat distribution, systemic inflammation, insulin resistance, leptin and the serum and subcutaneous adipose tissue gene expression levels of tumor necrosis factor-alpha (TNF-alpha), adiponectin and the inhibitor kappa B-alpha (IkB-alpha), in subjects with a wide range of body mass index (BMI). We also wanted to determine which of these variables was most closely related to adiponectin gene expression and adipocyte NF-kB transcriptional power. METHODS: A total of 27 women aged between 50 and 80 years, with BMI ranging from 22.1 to 53.3 kg/m(2), were studied. In all subjects BMI, waist circumference, body composition by dual X-ray absorptometry, triglycerides, cholesterol, high-density lipoprotein cholesterol (HDL-Ch), glucose, insulin, homeostasis model assessment of insulin resistance (HOMA), high-sensitive C-reactive protein (hs-CRP), serum adiponectin, leptin and TNF-alpha were evaluated. Subcutaneous adipose tissue biopsies were taken from the abdomen of all subjects and the mRNA levels of adiponectin, TNF-alpha and IkB-alpha were determined. RESULTS: BMI and waist circumference were associated positively with leptin, HOMA, and hs-CRP, and negatively with HDL-Ch; waist was also associated with adiponectin and IkB-alpha mRNA. HOMA was negatively associated with serum adiponectin and adiponectin mRNA. Hs-CRP was negatively associated with IkB-alpha mRNA, and was positively associated with HOMA. Step-down multiple regression analysis was performed to determine the joint effects of BMI, waist circumference, triglycerides, HDL-Ch, HOMA, hs-CRP, leptin, serum and TNF-alpha mRNA on adiponectin gene expression: waist circumference and leptin were both included in the best fitting regression equation for predicting adiponectin gene expression (R(2)=0.403, P=0.006). Stepwise multiple regression analysis was performed, considering IkB-alpha mRNA as a dependent variable and BMI, waist, HDL-Ch, HOMA, hs-CRP and adiponectin mRNA as independent variables. Adiponectin mRNA was the only variable to enter the regression (R(2)=0.406, P<0.001). CONCLUSION: Our results suggest that abdominal adiposity and leptin are independent predictors of adiponectin gene expression and that in human adipocytes, adiponectin gene expression is strongly related to IkB-alpha mRNA.

Effect of native somatostatin on Sphincter of Oddi motility in patients with acute recurrent pancreatitis. A pilot study with Ultrasound-Secretin test.

BACKGROUND: The effect of native somatostatin on Sphincter of Oddi motility still remains controversial. Sphincter of Oddi inhibition was demonstrated at manometry in patients in the acute phase of alcoholic pancreatitis. Other investigators showed marked somatostatin-induced impairment of bile flow by hepato-biliary scintigraphy. AIM: Aim of the study was to determine the effects of therapeutical doses of exogenous somatostatin on Sphincter of Oddi motility. PATIENTS AND METHODS: We studied eight patients (two men, six women, age 18-42), in the quiescent phase of idiopathic recurrent pancreatitis. We directly studied Sphincter of Oddi motility by perendoscopic manometry and, indirectly, secretin-stimulated pancreatic juice outflow by Ultrasound-Secretin test. The two tests were repeated before and after somatostatin infusion. RESULTS: Manometry was performed in two patients. After 250 microg somatostatin bolus the sphincter showed an increase of motor activity. At Ultrasound-Secretin test mean diameters were significantly larger at 40-60 min evaluation intervals during 250 microg/h somatostatin infusion as compared to saline infusion, showing a delayed pancreatic duct emptying. CONCLUSIONS: Acute administration of somatostatin seems to induce an excitatory effect on Sphincter of Oddi motility, with impaired pancreatic outflow in patients in the quiescent phase of recurrent pancreatitis.

Health consequences of obesity in the elderly: a review of four unresolved questions.

Obesity prevalence is growing progressively even among older age groups. Controversy exists about the potential harms of obesity in the elderly. Debate persists about the relation between obesity in old age and total or disease-specific mortality, the definition of obesity in the elderly, its clinical relevance, and about the need for its treatment. Knowledge of age-related body composition and fat distribution changes will help us to better understand the relationships between obesity, morbidity and mortality in the elderly. Review of the literature supports that central fat and relative loss of fat-free mass may become relatively more important than BMI in determining the health risk associated with obesity in older ages. Weight gain or fat redistribution in older age may still confer adverse health risks (for earlier mortality, comorbidities conferring independent adverse health risks, or for functional decline). Evaluation of comorbidity and weight history should be performed in the elderly in order to generate a comprehensive assessment of the potential adverse health effects of overweight or obesity. The risks of obesity in the elderly have been underestimated by a number of confounders such as survival effect, competing mortalities, relatively shortened life expectancy in older persons, smoking, weight change and unintentional weight loss. Identification of elderly subjects with sarcopenic obesity is probably clinically relevant, but the definition of sarcopenic obesity, the benefits of its clinical identification, as well as its relation to clinical consequences require further study. Studies on the effect of voluntary weight loss in the elderly are scarce, but they suggest that even small amounts of weight loss (between 5-10% of initial body weight) may be beneficial. In older as well as in younger adults, voluntary weight loss may help to prevent the adverse health consequences of obesity.

Physical disability and muscular strength in relation to obesity and different body composition indexes in a sample of healthy elderly women.

OBJECTIVES: The aim of the present study was to test the association between muscular strength, functional limitations, body composition measurements and indexes of sarcopenia in a sample of community-dwelling, elderly women at the high end of the functional spectrum. DESIGN: Cross-sectional. SUBJECTS: In all, 167 women aged 67-78 y were selected from the general population in central Verona. A group of 120 premenopausal healthy women aged 20-50 y represented the young reference group. MEASUREMENTS: Body weight, height, body mass index (BMI) and the presence of acute and chronic conditions were evaluated in each subject. Body composition was measured by dual-energy X-ray absorptiometry (DXA). Physical functioning was assessed using a modified version of the Activities of Daily Living Scale. Dominant leg isometric strength was measured with a Spark Handheld Dynamometer. RESULTS: Elderly women with BMI higher than 30 kg/m(2) and in the highest quintile of body fat percent showed a significantly higher prevalence of functional limitation. In our population study, about 40% of sarcopenic elderly women and 50% of elderly women with high body fat and normal muscle mass were functionally limited. The prevalence of functional limitation significantly increased in subjects with class II sarcopenia, defined according to the skeletal muscle mass index (SMI=skeletal muscle mass/body mass x 100). In logistic regression models, after adjusting for age and different chronic health conditions, subjects with BMI higher than 30 kg/m(2), in the highest quintile of body fat, or with high body fat and normal muscle mass or class II sarcopenia according to SMI, had a 3-4 times increased risk of functional limitations. Finally, isometric leg strength was significantly lower in subjects in the lowest quintile of relative muscle mass and in sarcopenic and sarcopenic obese women. CONCLUSIONS: High body fat and high BMI values were associated with a greater probability of functional limitation in a population of elderly women at the high end of the functional spectrum. Among the different indexes of sarcopenia used in this study, only SMI predicted functional impairment and disability. Isometric leg strength was significantly lower in subjects with sarcopenia and sarcopenic obesity.

Relation between body composition, fat distribution, and lung function in elderly men.

BACKGROUND: Body composition changes with age, with increases in fat mass and visceral fat and declines in skeletal muscle mass; lung function also declines with age. Age-related changes in body composition and fat distribution may be associated with the pulmonary impairment observed in the elderly. OBJECTIVE: Our goal was to evaluate the relations between body composition, fat distribution, and lung function in elderly men. DESIGN: We studied 97 men aged 67-78 y with body mass indexes (BMIs; in kg/m2) ranging from 19.8 to 37.1. Body composition was evaluated by using dual-energy X-ray absorptiometry and fat distribution was evaluated by using waist and hip circumferences, waist-to-hip ratio, and sagittal abdominal diameter (SAD). Spirometry was done in all subjects and the distance walked by each subject during a 6-min walking test was evaluated as was leg strength. RESULTS: A significant negative correlation was found between adiposity, fat distribution indexes, forced vital capacity (FVC), and forced expiratory volume in 1 s (FEV1). A positive correlation was found between fat-free mass and FVC. After adjustment for age, height, and weight, SAD still correlated negatively with FVC and FEV1 (r = -0.367 and -0.348, respectively; P < 0.01), whereas percentage body fat and fat mass correlated negatively and fat-free mass correlated positively with FVC (r = -0.313, -0.323, and 0.299, respectively; all P < 0.01). After the sample was subdivided by tertile of fat-free mass adjusted for age and BMI, FVC and FEV1 were significantly lower in the lowest fat-free mass tertile (P < 0.01). Stepwise multiple regression analysis performed with use of lung function variables as the dependent variables and age, height, fat mass, fat-free mass, waist circumference, and SAD as the independent variables showed that 3 variables entered the regression for predicting FVC: height, which entered the regression first; SAD, which entered second; and fat-free mass, which entered third. Only 2 variables entered the regression for predicting FEV1: height, which entered the regression first, and SAD, which entered second. CONCLUSION: Our cross-sectional data show a significant association between body composition, fat distribution, and lung function in elderly men.

Homocysteine and life-style in the elderly.

Elevated homocysteine increases the risk of vascular diseases but little information is available about this issue in the elderly. The aim of this cross-sectional study was to evaluate the relationships between homocysteinemia and gender, anthropometric, and life-style characteristics in a community-dwelling elderly population (65 men and 120 women; 67-78 years). Basal plasma homocysteine levels were determined by High Performance Liquid Chromatography (HPLC). Clinical records, and nutritional and anthropometric variables were collected in all subjects. Body composition was evaluated in all subjects by Dual energy X-ray Absorptiometry (DXA). Thirty-three percent of women and 66% of men had hyper-homocysteinemia. In women, a positive correlation was present between homocysteinemia, age, diastolic blood pressure and plasmatic creatinine, and a negative correlation between homocysteine, fiber intake and folates. In males, there was a positive correlation between plasma homocysteine, age, and body mass index. Multiple regression analysis showed that fat-free mass, cigarette smoking, fiber intake, vitamin B6 and total kcal intake accounted for 18% of homocysteine variance in males (R2 = 0.18, p<0.05). Significantly higher homocysteine values were found in women with a history of cardiovascular disease than in those without (16.6 +/- 9.4 vs 13.8 +/- 4.4 micromol/L, p<0.05). Homocysteinemia was significantly higher in elderly men compared to women (16.7 +/- 4.7 vs 15.3 +/- 7.6; p<0.05). Gender differences in homocysteine disappeared after adjusting for fat-free mass. This study confirms the age-related increase in plasma homocysteine. Life-style characteristics seem to influence significantly homocysteine levels in the elderly. Our study shows that gender effects on homocysteine may be attributed to differences in body composition.

Waist circumference and abdominal sagittal diameter as surrogates of body fat distribution in the elderly: their relation with cardiovascular risk factors.

OBJECTIVE: To evaluate the relationship between supine sagittal abdominal diameter (SAD) and other indicators of body fat distribution with cardiovascular (CVD) risk factors in the elderly. SUBJECTS: One-hundred and forty-six women aged from 67 to 78 y with a body mass index (BMI) ranging from 18.7 to 50.6 kg/m2 and 83 men aged between 67 and 78 y with BMI ranging from 19.8 to 37.1 kg/m2. MEASUREMENT: Body fat distribution was assessed using anthropometric indicators: waist circumference, SAD, waist-to-hip ratio (WHR), waist-to-height ratio and SAD-to-thigh ratio. RESULTS: In women, there was a negative correlation between HDL-cholesterol and body weight, BMI, waist, SAD, WHR, waist-to-height ratio and SAD-to-thigh ratio. A significant association was found between triglycerides, basal glucose, 2 h glucose during oral glucose tolerance test (OGTT), systolic blood pressure (SBP), diastolic blood pressure (DBP) and anthropometric variables. In men a negative correlation was found between HDL-cholesterol and all the anthropometric variables. A significant association was found between triglycerides, DBP and body weight, BMI, waist, SAD and waist-to-height ratio. In women, after adjusting for age and BMI, a significant correlation was observed between waist and HDL-cholesterol, triglycerides and basal glucose. This was also seen with SAD and SAD-to-thigh ratio and triglycerides, basal and 2 h glucose. In men, after adjusting for age and BMI a significant correlation was found between SAD and HDL-cholesterol and triglycerides. When adjustments were made for age and waist, the correlations between BMI and metabolic variables as well between BMI and SBP and DBP were no longer significant. CONCLUSIONS: Our study shows that indicators of body fat distribution are associated with CVD risk factors in the elderly independently of BMI. Our data also show that waist and SAD are the anthropometric indicators of fat distribution which are most closely related to CVD risk factors in old age.