ISSN:1068-3097    

出版商:OVID    

年代:1996

数据来源: OVID

摘要:

Between 1980 and 1990 there was an unprecedented increase in body weight and prevalence of obesity in the United States. The mean weight of adults. 20 through 74 years of age increased 3.6 kg, whereas mean height increased less than 1 cm. The increase occurred in both sexes, all races, and all age strata except women over 60 years of age. The increase in weight is plausibly explained by an increase in caloric intake. Any accompanying reduction in energy expenditure would have augmented the effect of increased calories, but it appears that leisure time physical activity did not decline in adults Although smoking cessation is associated with excess weight gain, the growing number of ex-smokers can account for only a fraction of the population's increase in body weight There is a strong relationship between relative body weight and risk of non-insulin-dependent diabetes mellitus (NIDDM). A relationship also exists between physical activity and risk of NIDDM, but it is not well defined (in terms of a relationship between type, frequency, and intensity of exercise). Given the increase in body weight across the population, together with the fact that physical activity has been constant or decreased, an increase in risk for NIDDM would be expected. No firm evidence of an increase in incidence or prevalence of NIDDM has emerged from the National Health Interview Surveys that were conducted annually. Possible explanations for this discrepancy are considered.

ISSN:1068-3097    

出版商:OVID    

年代:1996

数据来源: OVID

摘要:

The interaction between obesity and non-insulin-dependent diabetes mellitus has been extensively studied, but how obesity is associated with insulin resistance and glucose intolerance remains incompletely understood. This review deals with a new concept concerning the roles of plasma tree fatty acids and glucose levels on muscle metabolism in obesity and non-insulin-dependent diabetes mellitus; namely, that hyperglycemia affects both lipid and glucose muscle metabolism (a corollary of the Randle glucose-fatty acid fuel competition hypothesis). The impairment of insulin's ability to increase muscle blood flow in obese patients and the role of hyperinsulinemia after an oral glucose tolerance test are presented. The possible relevance for human obesity of the isolation and cloning of the ob gene, the recent results concerning a role of the β3adrenergic receptor in obesity, and the recent results concerning tumor necrosis factor α in insulin resistance are also briefly described.

ISSN:1068-3097    

出版商:OVID    

年代:1996

数据来源: OVID

摘要:

Insulin resistance is a ubiquitous correlate of obesity and a central component of non-insulin-dependent diabetes mellitus. However, the molecular mechanisms that link obesity to insulin resistance have been obscure. Recent data suggest that the cytokine tumor necrosis factor-α produced by fat in obesity may be a key component of the insulin-resistant state. We provide an overview of tumor necrosis factor-α signaling mechanisms and review the most recent data concerning the role of tumor necrosis factor-α in obesity-related insulin resistance and non-insulin-dependent diabetes mellitus.

ISSN:1068-3097    

出版商:OVID    

年代:1996

数据来源: OVID

摘要:

Genetic approaches to the understanding of obesity have long been an important tool for gaining insights into this complicated disease. Rodent models offer ease of manipulation and simplicity of use over many other models, including humans. Recent advances in the characterization of mouse monogenic lesions and the identification of the genes are highlighted. In particular, the agouti, ob, and far genes are discussed in some detail. Also, a brief overview of the techniques used to isolate these genes is presented.

ISSN:1068-3097    

出版商:OVID    

年代:1996

数据来源: OVID

摘要:

This review describes the most recent findings on the genetic epidemiology of the causes of human excess body weight or obesity. The emphasis is on single-gone effects, as identified by a variety of approaches. Evidence from Mendelian disorders that have obesity as one of their features is considered. The reports on candidate genes and other molecular markers that have appeared recently are summarized. Four loci have been shown to be linked with body-mass index or body fat by the sib-pair analytical method, with P values loss than or equal to 0.004. These loci are ACP1 (2p25), TNF-α (6p21.3), KEL (7q33), and ADA (20q12–13.1). Replication studies are clearly desirable.

ISSN:1068-3097    

出版商:OVID    

年代:1996

数据来源: OVID

摘要:

The discovery of the adipose tissue hormone leptin significantly changed our understanding of obesity and the insulin resistance associated with this disease. It remains uncertain whether the search for the etiology of the insulin resistance in human obesity should concentrate on tracing the primary defect at the cellular level (in the insulin receptor signaling cascade) or on searching for the afferent and efferent pathways of leptin in the brain involved in the control of appetite and macronutrient disposal. Recent developments concerning both concepts are briefly discussed. Treatment of insulin resistance in obesity can be beneficial if combined with measures limiting appetite and dietary fat intake.

ISSN:1068-3097    

出版商:OVID    

年代:1996

数据来源: OVID

摘要:

White and brown adipose tissues serve important yet opposite functions; energy storage and energy expenditure. In contrast to white fat, brown fat is highly vascular, densely innervated by sympathetic nerves, and (unlike all other tissues) possesses uncoupling protein. Uncoupling protein is an inner-membrane mitochondrial protein that uncouples respiration in a highly regulated fashion. Because of this capacity, energy expenditure in brown adipose tissue can range over many orders of magnitude and, when maximally stimulated, can contribute importantly to total-body energy expenditure. Prevailing evidence, obtained mostly through studies in rodents, indicates that brown adipose tissue plays an important role in regulating total body fat stores. Whether it plays the same role in humans remains to be determined.

ISSN:1068-3097    

出版商:OVID    

年代:1996

数据来源: OVID

摘要:

The hypothalamus, a region key to regulating food intake, energy expenditure, and body weight, contains many peptides and neurotransmitters that influence energy homeostasis. The neurons in the arcuate nucleus that express neuropeptide Y and project to the paraventricular nucleus have been the subject of particular attention. Neuropeptide Y injected into the paraventricular nucleus induces hyperphagia and weight gain and the arcuato-paraventricular neurons are implicated both in homeostatic responses to energy deficit and in causing obesity in rodents. Some potential modulators of the activity of these neurons are insulin and leptin (inhibitory) and glucocorticoids (stimulatory). Selective neuropeptide Y antagonists are being developed that could act on putative feeding neuropeptide Y receptors in the hypothalamus to induce weight loss; such agents may be useful in treating obesity and non-insulin-dependent diabetes mellitus. The relative importance of neuropeptide Y and other appetite-modulating peptides, such as the appetite stimulant galanin and possibly satiety agents (cholecystokinin and bombesin), is unknown.

ISSN:1068-3097    

出版商:OVID    

年代:1996

数据来源: OVID

摘要:

Pharmaceutical companies have searched for years for a drug for the treatment of obesity that could safely augment thermo-genesis and thus increase energy expenditure. The discovery of a third β-adrenergic receptor, the β3or atypical adrenoceptor, and the discovery in small mammals that drugs targeted to this receptor prevent or correct obesity (and unexpectedly hyperglycemia as well) have intensified this search. As yet no fully selective or active β3adrenoceptor agonist against the human receptor has been available for testing. Several partially selective and active agonists have been tested in humans, with encouraging effects on thermo-genesis and insulin sensitivity. All have suffered from problems of toxicity, lack of selectivity for the human β3adrenoceptor resulting in unacceptable tachycardia (β1effect) or tremor (β2effect) or lack of full activity at the human β3adrenoceptor. A recently introduced drug, CL 316,243, is in phase II clinical trials. It is a selective, but only partial, agonist for the human B3AR. The important question is whether the remarkable effects of these drugs on obesity and diabetes in small mammals will translate to the human conditions. As yet this question cannot be answered because of differences in the expression, activity, and pharmacology of β3adrenoceptors between small mammals and large mammals (including humans) and because of the lack of an available fully selective and active agonist against the human receptor.

ISSN:1068-3097    

出版商:OVID    

年代:1996

数据来源: OVID