Increased insulin sensitivity and obesity resistance in mice lacking the protein tyrosine phosphatase-1B gene.
(17/23597)
Protein tyrosine phosphatase-1B (PTP-1B) has been implicated in the negative regulation of insulin signaling. Disruption of the mouse homolog of the gene encoding PTP-1B yielded healthy mice that, in the fed state, had blood glucose concentrations that were slightly lower and concentrations of circulating insulin that were one-half those of their PTP-1B+/+ littermates. The enhanced insulin sensitivity of the PTP-1B-/- mice was also evident in glucose and insulin tolerance tests. The PTP-1B-/- mice showed increased phosphorylation of the insulin receptor in liver and muscle tissue after insulin injection in comparison to PTP-1B+/+ mice. On a high-fat diet, the PTP-1B-/- and PTP-1B+/- mice were resistant to weight gain and remained insulin sensitive, whereas the PTP-1B+/+ mice rapidly gained weight and became insulin resistant. These results demonstrate that PTP-1B has a major role in modulating both insulin sensitivity and fuel metabolism, thereby establishing it as a potential therapeutic target in the treatment of type 2 diabetes and obesity. (+info)
Evaluation and treatment of childhood obesity.
(18/23597)
The prevalence of childhood obesity in the United States has risen dramatically in the past several decades. Although 25 to 30 percent of children are affected, this condition is underdiagnosed and undertreated. Hormonal and genetic factors are rarely the cause of childhood obesity; unnecessary diagnostic evaluations can be avoided with a careful history and physical examination. Because obese children may suffer life-long physical and emotional consequences, it is imperative to discuss prevention with parents during well-child examinations. All obese children should be screened for cardiac risk factors, as well as for possible orthopedic, dermatologic and psychiatric sequelae. Treatment should be initiated when the trend in increasing weight obviously surpasses the trend in increasing height. Treatment plans should include reasonable weight-loss goals, dietary and physical activity management, behavior modification and family involvement, which may include weight loss in the parents. Anorexiant medications are not approved by the U.S. Food and Drug Administration for use in pediatric populations. (+info)
Interactions between the neuropeptide Y system and the hypothalamic-pituitary-adrenal axis.
(19/23597)
The aim of this paper is to review the present knowledge of interactions between the neuropeptide Y (NPY) system and the hypothalamic-pituitary-adrenal (HPA) axis. On the basis of in vitro and in vivo studies of various animal species, we review the effects of NPY on all levels of HPA axis activity. We also describe the effects of glucocorticosteroids on the NPY system in the hypothalamus, including interactions between glucocorticosteroids and insulin. On the basis of available literature, we discuss the role of these interactions in the control of food intake and in the pathogenesis of obesity. (+info)
GH-binding protein in obese men with varying glucose tolerance: relationship to body fat distribution, insulin secretion and the GH-IGF-I axis.
(20/23597)
Bioelectrical impedance for measurement of total body fat and computed tomography for visceral and subcutaneous fat at umbilicus levels were performed in 34 obese and 10 lean men. Insulin secretion in response to an oral glucose tolerance test (OGTT) and a GH stimulation test by L-dopa, growth hormone-binding protein (GHBP) and IGF-I were measured. Obese subjects were divided into three groups according to the OGTT. The obese type II diabetes mellitus group had the highest GHBP levels and the most visceral fat. GHBP levels were most strongly correlated with the ratio of visceral fat area to body weight (VWR) above any other parameters (r = 0.725, P<0.001). The insulin and free fatty acid (FFA) areas under curves (AUC) during the OGTT, and the IGF-I level, were also positively correlated with GHBP levels (r = 0.474, P<0.005; r = 0.572, P<0.005; r = 0.453. P<0.005). GH-AUC to the L-dopa stimulation test was negatively correlated with GHBP levels (r = -0.432. P<0.005). Stepwise multiple linear regression analysis showed that VWR, FFA-AUC and insulin-AUC significantly contributed to the variability of GHBP (r2 = 0.58). In conclusion, we demonstrated that: (i) visceral fat amount mainly determined GHBP levels in obese men with varying glucose tolerance: (ii) hyperglycemia per se did not influence the GHBP level, whereas insulin and FFA could play a role in regulation of GHBP: and (iii) although GH was not the main regulator of GHBP, the unchanged IGF-I level despite GH hyposecretion suggests that increased GHBP levels reflect GH hypersensitivity in order to compensate for decreased GH secretion in obesity. (+info)
Effect of leptin deficiency on metabolic rate in ob/ob mice.
(21/23597)
Reduced metabolic rate may contribute to weight gain in leptin-deficient (ob/ob) mice; however, available studies have been criticized for referencing O2 consumption (VO2) to estimated rather than true lean body mass. To evaluate whether leptin deficiency reduces energy expenditure, four separate experiments were performed: 1) NMR spectroscopy was used to measure fat and nonfat mass, permitting VO2 to be referenced to true nonfat mass; 2) dietary manipulation was used in an attempt to eliminate differences in body weight and composition between ob/ob and C57BL/6J mice; 3) short-term effects of exogenous leptin (0.3 mg. kg-1. day-1) on VO2 were examined; and 4) body weight and composition were compared in leptin-repleted and pair-fed ob/ob animals. ob/ob animals had greater mass, less lean body mass, and a 10% higher metabolic rate when VO2 was referenced to lean mass. Dietary manipulation achieved identical body weight in ob/ob and C57BL/6J animals; however, despite weight gain in C57BL/6J animals, percent fat mass remained higher in ob/ob animals (55 vs. 30%). Exogenous leptin increased VO2 in ob/ob but not control animals. Weight loss in leptin-repleted ob/ob mice was greater than in pair-fed animals (45 vs. 17%). We conclude, on the basis of the observed increase in VO2 and accelerated weight loss seen with leptin repletion, that leptin deficiency causes a reduction in metabolic rate in ob/ob mice. In contrast, these physiological studies suggest that comparison of VO2 in obese and lean animals does not produce useful information on the contribution of leptin to metabolism. (+info)
Extent and composition of coronary lesions in relation to fat distribution in women younger than 50 years of age.
(22/23597)
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)
Report of a National Institutes of Health--Centers for Disease Control and Prevention workshop on the feasibility of conducting a randomized clinical trial to estimate the long-term health effects of intentional weight loss in obese persons.
(23/23597)
A workshop was convened in 1997 by the National Institutes of Health and the Centers for Disease Control and Prevention to consider the need for and feasibility of conducting a randomized clinical trial to estimate the long-term health effects of intentional weight loss in obese persons. Although the benefits of weight loss in obese individuals may seem obvious, little information is available showing that intentional weight loss improves long-term health outcomes. Observational studies may be unable to provide convincing answers about the magnitude and direction of the health effects of intentional weight loss. Workshop participants agreed that a well-designed randomized clinical trial could answer several questions necessary for developing a rational clinical and public health policy for treating obesity. Such information will ultimately provide needed guidance on the risks and benefits of weight loss to health care providers and payers, as well as to millions of obese Americans. (+info)
Cardiorespiratory fitness, body composition, and all-cause and cardiovascular disease mortality in men.
(24/23597)
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)