Elena Zoico

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/m2 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 × 100). In logistic regression models, after adjusting for age and different chronic health conditions, subjects with BMI higher than 30 kg/m2, 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.

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.

Body composition changes in stable-weight elderly subjects: the effect of sex.

Background and aims: Although cross-sectional and longitudinal studies have shown age-related changes in body composition and fat distribution, they may be related to body weight changes. The aim of this study was to evaluate yearly age-related changes in body composition and fat distribution, over a two-year period, in 101 women and 60 men (age range: 68 to 78 years at baseline). Methods: Body composition was evaluated by dual energy X-ray absorptiometry (DXA), and fat distribution by waist and hip circumferences and waist-to-hip circumference ratio. Baseline free testosterone, IGF-1 and serum albumin were evaluated in all subjects, as well as physical activity. Clinical evaluation was performed at baseline and yearly in order to exclude subjects with any condition inducing pathological changes in body composition or fat distribution. Subjects with a weight change >5% of their baseline body weight during the study period, were excluded. Results: Significant increases occurred in Body Mass Index (BMI) (1.18% in women, 1.13% in men), waist (1.75% in women, 1.39% in men), and hip circumference (1.06% in women, 1.31% in men), whereas height decreased significantly in both men (0A2%) and women (0.55%). Significant increases in total body fat (1.31%) and percent body fat (1.27%) were observed in women but not in men. Lean body mass did not change significantly throughout the study in either sex. Significant losses in leg muscle mass and appendicular skeletal muscle mass (ASM), calculated as the sum of arm and leg fat-free soft tissue, were observed in men (respectively 3.56 and 2.77%) and women (respectively 2A1 and 1.59%). A significant decrease in ASM adjusted by stature (ASM/height2), a proposed proxy for sarcopenia, was found in men only (1.97%). The rates of loss in leg muscle mass and appendicular muscle mass were significantly higher in men than in women, even after adjusting for free testosterone, IGF-1, physical activity and serum albumin. Conclusions: These data demonstrate significant changes in body composition and fat distribution in independently living, weight-stable elderly men and women. These changes are dependent on sex and independent of physical activity, hormones or serum albumin.

Adiponectin gene expression and adipocyte diameter: a comparison between epicardial and subcutaneous adipose tissue in men

INTRODUCTION Interest has recently focused on epicardial fat, but little is known about epicardial adipocyte size and its relation with insulin resistance and adipokines. METHODS Biopsies were collected from subcutaneous, epicardial-, and peritoneal fat from 21 males undergoing elective cardiac surgery either for coronary artery bypass grafting (n=11) or for valve replacement (n=10). We assessed epicardial adipocyte size, comparing it with that from subcutaneous fat and peritoneal fat. The adipocyte size was determined by using collagenase digestion of adipose tissue, separation of adipocytes by centrifugation, methylene blue staining of the nuclei, and measurement of the cell diameter. Patients weight, height, body mass index, waist, as well as glucose, insulin, homeostatic model assessment index, adiponectin, and leptin serum levels were determined. Adiponectin mRNA levels were determined by real-time polymerase chain reaction on subcutaneous fat and epicardial fat biopsies. RESULTS Adipocytes in epicardial fat were significantly smaller than those in subcutaneous and peritoneal fat. The adipocyte size in epicardial fat correlated positively with insulin resistance and serum leptin, and correlated negatively with serum and mRNA expression of adiponectin. Adiponectin mRNA expression in epicardial fat was significantly lower than in subcutaneous fat. Adipocyte size in epicardial fat was significantly smaller in valve-replacement patients than in coronary artery bypass graft patients. Adiponectin gene expression was lower in the latter than in the former, although not significantly. CONCLUSIONS Adipocytes in epicardial fat are smaller than those in peritoneal and subcutaneous fat. Adipocyte size, both in epicardial and in subcutaneous fat, is positively related with insulin resistance, shows negative association with local adiponectin gene expression, and is decreased in subjects with coronary artery disease. Adiponectin gene expression is significantly lower in epicardial- than in subcutaneous fat.

Relationship between leptin levels and bone mineral density in the elderly

objective To assess the relationship between circulating leptin levels, bone mineral content and density in the elderly.

Obesity and gastro-esophageal acid reflux: physiopathological mechanisms and role of gastric bariatric surgery.

Background: Controversial findings about the relationships between obesity and gastro-esophageal reflux have been reported, as well as about the effects of weight loss and bariatric surgery on reflux. The aims of this study were to evaluate esophageal motility and gastro-esophageal acid circadian patterns in obese patients and to test the effects of vertical banded gastroplasty (VBG) on these parameters. Methods: 14 obese subjects (BMI 36-53 kg/m2), 4 men, 10 women, 27-61 years old, admitted for elective bariatric surgery, underwent clinical evaluation, upper endoscopy, esophageal manometry and gastroesophageal pH monitoring. Evaluations were repeated 6 to 12 months after gastric surgery that consisted of a VBG (7 patients), accompanied in the other 7 patients with an anti-reflux procedure (fundoplication). Manometric and pH-metric findings in the obese patients were compared with a normal-weight control group before and after the two different surgical treatments. Results: Gastro-esophageal reflux was significantly more frequent in obese (57.1%) than in control group (7.1%). Esophageal motility in obese subjects was not different from controls. After VBG alone, we found a reduction in basal lower esophageal sphincter (LES) pressure and an increase of acid reflux. When VBG was accompanied by fundoplication, basal LES pressure increased and acid reflux frequency decreased. Conclusions: Obesity is associated with gastroesophageal reflux. VBG reduced weight, but not gastro-esophageal acid reflux. Therefore, in our population, this operation cannot be considered as an antireflux procedure.

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.

Adiponectin gene expression and adipocyte NF-κB 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-α), adiponectin and the inhibitor kappa B-alpha (IkB-α), 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/m2, 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-α were evaluated. Subcutaneous adipose tissue biopsies were taken from the abdomen of all subjects and the mRNA levels of adiponectin, TNF-α and IkB-α 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-α mRNA. HOMA was negatively associated with serum adiponectin and adiponectin mRNA. Hs-CRP was negatively associated with IkB-α 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-α 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-α 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 (R2=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-α mRNA.

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.