Insulin resistance of muscle glucose transport in male and female rats fed a high-sucrose diet.
(17/12479)
It has been reported that, unlike high-fat diets, high-sucrose diets cause insulin resistance in the absence of an increase in visceral fat and that the insulin resistance develops only in male rats. This study was done to 1) determine if isolated muscles of rats fed a high-sucrose diet are resistant to stimulation of glucose transport when studied in vitro and 2) obtain information regarding how the effects of high-sucrose and high-fat diets on muscle insulin resistance differ. We found that, compared with rat chow, semipurified high-sucrose and high-starch diets both caused increased visceral fat accumulation and insulin resistance of skeletal muscle glucose transport. Insulin responsiveness of 2-deoxyglucose (2-DG) transport measured in epitrochlearis and soleus muscles in vitro was decreased approximately 40% (P < 0.01) in both male and female rats fed a high-sucrose compared with a chow diet. The high-sucrose diet also caused resistance of muscle glucose transport to stimulation by contractions. There was a highly significant negative correlation between stimulated muscle 2-DG transport and visceral fat mass. In view of these results, the differences in insulin action in vivo observed by others in rats fed isocaloric high-sucrose and high-starch diets must be due to additional, specific effects of sucrose that do not carry over in muscles studied in vitro. We conclude that, compared with rat chow, semipurified high-sucrose and high-cornstarch diets, like high-fat diets, cause increased visceral fat accumulation and severe resistance of skeletal muscle glucose transport to stimulation by insulin and contractions. (+info)
PPARgamma activation in human endothelial cells increases plasminogen activator inhibitor type-1 expression: PPARgamma as a potential mediator in vascular disease.
(18/12479)
Plasminogen activator inhibitor type-1 (PAI-1) is a major physiological inhibitor of fibrinolysis, with its plasma levels correlating with the risk for myocardial infarction and venous thrombosis. The regulation of PAI-1 transcription by endothelial cells (ECs), a major source of PAI-1, remains incompletely understood. Adipocytes also produce PAI-1, suggesting possible common regulatory pathways between adipocytes and ECs. Peroxisomal proliferator-activated receptor-gamma (PPAR)gamma is a ligand-activated transcription factor that regulates gene expression in response to various mediators such as 15-deoxy-Delta12, 14-prostaglandin J2 (15d-PGJ2) and oxidized linoleic acid (9- and 13-HODE). The present study tested the hypotheses that human ECs express PPARgamma and that this transcriptional activator regulates PAI-1 expression in this cell type. We found that human ECs contain both PPARgamma mRNA and protein. Immunohistochemistry of human carotid arteries also revealed the presence of PPARgamma in ECs. Bovine ECs transfected with a PPAR response element (PPRE)-luciferase construct responded to stimulation by the PPARgamma agonist 15d-PGJ2 in a concentration-dependent manner, suggesting a functional PPARgamma in ECs. Treatment of human ECs with 15d-PGJ2, 9(S)-HODE, or 13(S)-HODE augmented PAI-1 mRNA and protein expression, whereas multiple PPARalpha activators did not change PAI-1 levels. Introduction of increasing amounts of a PPARgamma expression construct in human fibroblasts enhanced PAI-1 secretion from these cells in proportion to the amount of transfected DNA. Thus, ECs express functionally active PPARgamma that regulates PAI-1 expression in ECs. Our results establish a role for PPARgamma in the regulation of EC gene expression, with important implications for the clinical links between obesity and atherosclerosis. (+info)
Low-density lipoprotein particle size is inversely related to plasminogen activator inhibitor-1 levels. The Insulin Resistance Atherosclerosis Study.
(19/12479)
High levels of plasminogen activator inhibitor-1 (PAI-1) and preponderance of small dense low-density lipoproteins (LDL) have both been associated with atherosclerotic disease and with the insulin resistance syndrome (IRS). In vitro studies have shown a stimulatory effect of various lipoproteins on PAI-1 release from different cells, including endothelial cells and adipocytes. The authors sought to investigate the relation of PAI-1 to LDL particle size in a large tri-ethnic population (n=1549) across different states of glucose tolerance. LDL size was determined by gradient gel electrophoresis, and PAI-1 was measured by a 2-site immunoassay, sensitive to free PAI-1. PAI-1 was inversely related to LDL size in the overall population (r=-0.21, P<0.0001), independent of gender and ethnicity. However, the authors found a significant interaction with glucose tolerance status (P=0.035). In univariate analysis, the association between PAI-1 and LDL size was most pronounced in subjects with normal glucose tolerance (NGT, r=-0.22, P<0.0001) and weaker in impaired glucose tolerance (IGT, r=-0.12, P=0.03) and type-2 diabetes (r=-0.10, P=0.02). After adjustment for demographic variables and metabolic variables known to influence PAI-1 levels (triglyceride and insulin sensitivity), a significant inverse relation of LDL size to PAI-1 levels was only present in NGT (P=0. 023). In subjects with IGT or overt diabetes, who usually have elevated PAI-1 levels, additional factors other than LDL size seem to contribute more importantly to PAI-1 levels. The demonstrated inverse relation of LDL size and PAI-1 levels provides one possible explanation for the atherogeneity of small dense LDL particles. (+info)
Extent and composition of coronary lesions in relation to fat distribution in women younger than 50 years of age.
(20/12479)
To ascertain the relationship between the extent and composition of coronary arterial lesions and the regional distribution of fat in healthy women younger than 50 years of age, a series of 30 forensic autopsy cases were investigated. Body height and weight, waist and hip circumferences, and the thickness of the subscapular and abdominal subcutaneous fat were measured; the body mass index (BMI) and waist-to-hip ratio (WHR) were calculated, and omental and mesenteric fat deposits were weighed. The extent of coronary lesions was measured by planimetry, and the thickness of the intima-media was measured by computerized image analysis. Intimal macrophage foam cells and smooth muscle cells were detected by immunohistochemistry, and macrophages were quantified. The intima media thickness in the left anterior descending artery, circumflex artery, and right coronary artery varied significantly across the tertiles of WHR when age and BMI were adjusted, being highest when WHR exceeded 0.87. The thickest lesions also contained the largest numbers of macrophage foam cells. The intima-media thicknesses were highest with increased amounts of intraperitoneal fat. These results indicate that the severity of clinically silent coronary lesions in younger female individuals is associated with increased WHR and increased amounts of intraperitoneal fat. These results emphasize the importance of WHR as a coronary risk indicator in younger women. (+info)
Cardiorespiratory fitness, body composition, and all-cause and cardiovascular disease mortality in men.
(21/12479)
BACKGROUND: Cardiorespiratory fitness and body fatness are both related to health, but their interrelation to all-cause and cardiovascular disease (CVD) mortality is unknown. OBJECTIVE: We examined the health benefits of leanness and the hazards of obesity while simultaneously considering cardiorespiratory fitness. DESIGN: This was an observational cohort study. We followed 21925 men, aged 30-83 y, who had a body-composition assessment and a maximal treadmill exercise test. There were 428 deaths (144 from CVD, 143 from cancer, and 141 from other causes) in an average of 8 y of follow-up (176742 man-years). RESULTS: After adjustment for age, examination year, cigarette smoking, alcohol intake, and parental history of ischemic heart disease, unfit (low cardiorespiratory fitness as determined by maximal exercise testing), lean men had double the risk of all-cause mortality of fit, lean men (relative risk: 2.07; 95% CI: 1.16, 3.69; P = 0.01). Unfit, lean men also had a higher risk of all-cause and CVD mortality than did men who were fit and obese. We observed similar results for fat and fat-free mass in relation to mortality. Unfit men had a higher risk of all-cause and CVD mortality than did fit men in all fat and fat-free mass categories. Similarly, unfit men with low waist girths (<87 cm) had greater risk of all-cause mortality than did fit men with high waist girths (> or =99 cm). CONCLUSIONS: The health benefits of leanness are limited to fit men, and being fit may reduce the hazards of obesity. (+info)
Racial differences in amounts of visceral adipose tissue in young adults: the CARDIA (Coronary Artery Risk Development in Young Adults) study.
(22/12479)
BACKGROUND: In several white populations, visceral adipose tissue (VAT) is a risk factor for development of type 2 diabetes and dyslipidemia. VAT can be accurately assessed by computed topography or magnetic resonance imaging, but is also estimated from anthropometric variables, such as waist-to-hip ratio, waist circumference, or sagittal diameter. To date, anthropometric variables have been used largely in whites and inadequate data are available to evaluate the validity of these variables in other groups. OBJECTIVES: The objectives of this study were to 1) determine whether amount of VAT in relation to total body fatness differs in different race and sex groups and 2) determine which anthropometric variables predict amount of VAT in different race and sex groups. DESIGN: We determined the amount and location of body fat, including assessment of VAT by computed tomography, in young adult white and black men and women participating in the 10-y follow-up of the CARDIA (Coronary Artery Risk Development in Young Adults) Study. RESULTS: Black men had less visceral fat (73.1+/-35.9 cm2) than white men (99.3+/-40 cm2), even when VAT was corrected for total body fatness. Black women were more obese than white women and thus had more visceral fat (75.1+/-37.5 compared with 58.6+/-35.9 cm2, respectively). This difference disappeared when corrected for total body fatness. CONCLUSIONS: Both waist circumference and sagittal diameter were good predictors of VAT in all groups. However, the nature of this relation differed such that race- and sex-specific equations will likely be required to estimate VAT from waist circumference or sagittal diameter. (+info)
Plasma leptin concentrations in obese children: changes during 4-mo periods with and without physical training.
(23/12479)
BACKGROUND: Little is known about the effects of physical training on plasma leptin concentrations in children. OBJECTIVE: We sought to determine the effects of 4-mo periods with and without physical training on leptin in obese children and to explore the determinants of leptin at baseline and in response to physical training. DESIGN: Participants were 34 obese 7-11-y-old children randomly assigned to engage in physical training during either the first or second 4 mo of the 8-mo study. RESULTS: Total body composition, visceral adiposity, and insulin were all positively correlated with leptin at baseline (P < or = 0.05); however, only fat mass was retained in the final stepwise regression (P = 0.0001, R2 = 0.57). Leptin decreased during the 4-mo periods of physical training and increased in the 4 mo after cessation of physical training (P < 0.001 for the time by group interaction). Decreases in leptin were greatest in children with higher pretraining leptin concentrations, those whose total mass increased least, and those whose insulin concentrations decreased most (P < or = 0.05); only pretraining leptin concentration (P = 0.009) and change in total mass (P = 0.0002) were retained in the final regression (R2 = 0.53). CONCLUSIONS: In obese children, leptin concentration decreased during 4 mo of physical training and increased during a subsequent 4-mo period without physical training, fat mass was highly correlated with baseline leptin, and greater reductions in leptin during 4 mo of physical training were seen in children with higher pretraining leptin and in those whose total mass increased least. (+info)
Dietary variety within food groups: association with energy intake and body fatness in men and women.
(24/12479)
BACKGROUND: Short-term experimental studies suggest that dietary variety may influence body fatness but no long-term human studies have been reported. OBJECTIVE: The purpose of this study was to determine whether dietary variety within food groups influences energy intake and body fatness. DESIGN: Seventy-one healthy men and women (aged 20-80 y), who provided accurate reports of dietary intake and completed a body-composition assessment, were studied. RESULTS: Dietary variety was positively associated with energy intake within each of 10 food groups (r = 0.27-0.56, P < 0.05). In multiple regression analysis with age and sex controlled for, dietary variety of sweets, snacks, condiments, entrees, and carbohydrates (as a group) was positively associated with body fatness (partial r = 0.38, P = 0.001) whereas variety from vegetables was negatively associated (partial r = -0.31, P = 0.01) (R2 = 0.46, P < 0.0001). In separate models, both a variety ratio (variety of vegetables/variety of sweets, snacks, condiments, entrees, and carbohydrates) and percentage dietary fat were significant predictors of body fatness (controlled for age and sex, partial r = -0.39 and 0.31, respectively, P < 0.01). However, dietary fat was no longer significantly associated with body fatness when the variety ratio and dietary fat were included in the same model. CONCLUSIONS: Our data, coupled with those of previous short-term studies, suggest that a high variety of sweets, snacks, condiments, entrees, and carbohydrates coupled with a low variety of vegetables promotes long-term increases in energy intake and body fatness. These findings may help explain the rising prevalence of obesity. (+info)