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Query: UMLS:C0028754 (obesity)
 124,988 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Virtually every metabolic disorder characterized by elevated plasma free fatty acid (FFA) levels is also associated with hypercorticoidism. For example, the glucocorticoid response to insulin-hypoglycemia is shown in this report to be greatly potentiated in Type I diabetic rats. Since glucocorticoids (corticosterone, in rats) potentiate lipolysis and promote gluconeogenesis, they exacerbate diabetes. We found that elevation of circulating FFA levels in normal rats (via Intralipid/heparin infusion) increased plasma levels of adrenocorticotropic hormone (ACTH) and corticosterone, and resulted in hyperglycemia. In vitro, however, cultured pituitary cells were relatively unaffected by FFA except at very high concentrations. Neither basal ACTH secretion nor the ACTH response to corticotropin-releasing hormone (CRH) was affected by pathophysiological molar ratios of FFA:BSA. Thus, the ACTH secretory response to FFA in vivo likely is mediated via neuroendocrine activation. Cultured adrenocortical cells, however, were stimulated by oleic acid and, to a lesser extent, by linoleic acid; saturated fatty acids were without effect. The latencies of oleic acid-induced steroidogenesis in vitro and Intralipid-induced corticosterone secretion in vivo were both about 60 min. We conclude that pathophysiological levels of circulating FFA (typical of diabetes, obesity, starvation, and consumption of high-fat diets) initiate a positive feedback loop between the adipocyte and the HPA axis, which ultimately exacerbates the symptoms of these disorders.
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PMID:Regulation of pituitary-adrenocortical activity by free fatty acids in vivo and in vitro. 778 56

The use of liquid protein products for treatment of obesity in the United States in the 1960s and '70s was associated with an increased risk of sudden cardiac death. The latter was related to long QT interval occurring in the absence of structural abnormalities of the heart. In an attempt to increase understanding of this phenomenon, the authors examined the possible role of diet-related circumstances. No evidence of increased incidence of sudden cardiac death or significant lengthening of QT interval in obesity, weight loss, starvation and dieting by methods other than liquid protein intake were found. It was concluded that sudden cardiac death during use of liquid protein products remains an enigma, but that other methods of properly medically supervised dieting appear to be safe.
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PMID:The enigma of sudden cardiac death related to dieting. 788 41

IRS-1 (insulin receptor substrate-1) is a major substrate for the insulin receptor tyrosine kinase. After phosphorylation by the insulin receptor, IRS-1 binds to the specific molecules which possess SH2 (src homology 2) domain such as 85 kDa subunit of phosphatidylinositol 3 kinase and may mediate insulin signals. The regulation of IRS-1 has been analyzed in animal models of insulin resistance, and its mechanism has been studied in culture cells. In animal models of insulin resistance, phosphorylation of IRS-1 was mainly regulated by the insulin receptor tyrosine kinase both in liver and muscle. However, IRS-1 protein level was differently regulated in muscle and liver. In muscle, IRS-1 protein decreased with dexamethasone treatment and in hypoinsulinemic states such as starvation and streptozotosine-induced diabetes and showed no change in hyperinsulinemic states such as obesity. In liver, IRS-1 protein increased with dexamethasone treatment and hypoinsulinemic states and decreased in hyperinsulinemic states. In cultured cell such as 3T3-L1 or 3T3-F442A adipocytes, IRS-1 was negatively regulated both by insulin and dexamethasone by different mechanisms. Insulin regulates the IRS-1 expression at protein level mainly by decreasing the half life of IRS-1 protein, and dexamethasone regulates it at mRNA level mainly by decreasing the half life of IRS-1 mRNA.
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PMID:[The expression of the insulin receptor substrate-1 (IRS-1) and analysis of its mechanism]. 789 62

Obesity in companion animals is a common clinical condition, and represents an important challenge to the veterinarian. This paper reports a study in which controlled calorie reduction was used to achieve weight loss in a group of dogs. The food allowance for the study provided approximately 209 kJ metabolisable energy (ME)/kg (target weight)0.75/day, with target weight 15% less than the dog's starting weight. The rate of weight loss achieved averaged approximately 1% per week over a 12 week period. Data reviewed from a second study in cats suggested that an energy intake of approximately 121 kJ ME/kg target weight/day, again with the target 15% less than the current weight, was an appropriate level for obtaining gradual weight loss in this species. These findings are discussed in relation to an alternative method of weight reduction, starvation. The potential value of exercise as an adjunct to controlled calorie reduction for achieving weight loss in companion animals is also considered.
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PMID:Clinical studies in the management of obesity in dogs and cats. 808 64

Glucose uptake into heart and skeletal muscle and white and brown adipose tissue is reduced in mice with gold thioglucose-induced obesity. After acute dieting (40% of lean control uptake) for 18 days, glucose uptake into tissues remains low despite consistently elevated serum insulin levels. This reduced glucose uptake may be a consequence of the raised serum fatty acid levels produced by dieting. When the reduced weight obese mice are pair-fed with lean controls, they gain weight. Glucose uptake into both muscle and adipose tissues is markedly increased, and the insulin resistance of both previous obesity and recent relative starvation is rapidly overcome at the level of the glucose uptake, but serum insulin levels and insulin secretion from islets of Langerhans isolated from these animals remain high. To maintain reduced weight, previously obese animals were fed 80% of lean control intake. In this situation, glucose uptake into the four tissues studied remained reduced (compared to lean controls), consistent with relative starvation. While tissue glucose uptake increases after dieting and re-feeding of obese animals, serum insulin levels remain high, indicating persistence of a degree of insulin resistance. Reduced-weight obese animals are energy-efficient in that they gain excess weight on the control intake.
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PMID:Tissue [1-14C] 2-deoxyglucose metabolism in the gold thioglucose obese mouse: effects of 'dieting'. 818 14

Type 2 diabetes is likely to be a polygenic disease, with a combination of major and minor genes affecting obesity, insulin secretion, and insulin action. Amongst these inputs, the 'thrifty genotype' hypothesis is most likely to apply to the predisposition to develop obesity, since the ability to store scarce fuels in periods of starvation could lead to obesity given a western lifestyle. Other genetic variations that were neutral with respect to food deprivation could be harmful with food excess. These could include 'defects' in islet cell function: examples could be mutations in the glucokinase gene and the genetic factors leading to amyloid deposition. The occurrence of associated lipid abnormalities or hypertension is probably due to additional specific genetic determinants that also become exaggerated by a modern lifestyle. The interactions between different genetic and environmental inputs are complex, and will probably be elucidated piecemeal as different genetic determinants are identified.
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PMID:Complex genetics of type 2 diabetes: thrifty genes and previously neutral polymorphisms. 821 Feb 95

The availability of food and the nutritional status of western Europeans have never been so good as in recent decades. However, we have not to go back too long to see that severe malnutrition also occurred in parts of western Europe. An example was the malnutrition and starvation causing high death rates in the western Netherlands in the early months of 1945, just before the end of the Second World War. Today there is an abundance of food in western Europe. Nevertheless we do warn people that the food, nutritious and delicious as it is, may be hazardous to health. Degenerative diseases like cardiovascular diseases, cancer, diabetes, obesity, osteoporosis and hypertension are very prevalent in our society. It is very likely that certain nutrients in foods do contribute both to the causes and prevention of these diseases. In this paper some new findings of the role of diet in health will be reviewed. This will be followed by a brief discussion on the status of nutrition research and training in Europe. Finally attention is asked for the need to start building-up a programme for nutritional leadership in Europe.
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PMID:The future of nutrition in Europe. 826 9

Total blood and plasma free amino acids and plasma urea levels were studied in fed and 24 h fasted Zucker rats. In fed animals there were no differences between obese and lean rats in the overall essential and non essential blood free amino acids. However, starvation reduced blood amino acid levels in the obese animals compared to the lean group, mainly due to changes in the plasma compartment. The reduction of available amino acids from plasma in the obese rats during starvation affected most of the amino acids, including the branched chain amino acids, which showed higher levels in the fed situation than in lean rats. Of particular interest is the opposite response to starvation in lean and obese Zucker rats concerning the plasma ratio of tryptophan (Trp) to the large neutral amino acids (LNAA) which could be implicated in the alteration of food intake and energy expenditure characteristic of obesity.
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PMID:Opposite response to starvation of Trp/LNAA ratio in lean and obese Zucker rats. 848 65

The hypothesis that a defect in glucose sensing by islets of fa/fa Zucker rats contributes to hyperinsulinemia in these animals was tested. Islets from lean and fa/fa rats were isolated by collagenase digestion and step-density gradient purification and then cultured overnight in Dulbecco's modified Eagle's medium containing 12.5 mM glucose. Obese rat islets were more sensitive to hypoglycemic glucose levels with half-maximal effective concentration (EC50) of 5.6 mM compared with an EC50 of 8.2 mM for lean rat islets. In contrast, responsiveness of both phenotypes to alpha-ketoisocaproate and quinine was similar. Mannoheptulose did not inhibit insulin secretion from fa/fa islets, although inhibitors of later events in the stimulus-secretion coupling pathway were normally inhibited by iodoacetate and diazoxide. Finally, starvation in vivo and culture of islets in low glucose concentrations (5 mM) in vitro both decreased glucose-stimulated insulin secretion from lean but not fa/fa rat islets. We conclude that fa/fa rat islets have an exaggerated insulin response to hypoglycemic stimuli, possibly as a result of a defect in B-cell glucokinase function.
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PMID:Evidence for defective glucose sensing by islets of fa/fa obese Zucker rats. 851 32

Graphic analyses have been used in the study of physiology as a means to better understand dynamic processes and to visualize the mechanisms of their interactions. A graphic analysis of glucose homeostasis was constructed by considering the main factors that influence glucose dynamics. The analysis is achieved by equating curves representing both the inflow and outflow of glucose from the circulation as dependent upon the serum insulin concentration. The point where these two curves intersect is the steady-state balance for blood glucose exchange and is termed the equilibrium point. With the use of this graphic depiction of glucose homeostasis, it is now possible to study the influence of multiple factors on glucose dynamics. A variety of metabolic states can also be analyzed by reconstructing the effects of the pathophysiology on the form and shape of the curves. Some of the metabolic states that have been analyzed by this technique include starvation, exercise, obesity, type I and type II diabetes mellitus, stress, hypopituitarism, hyperpituitarism, and hyperthyroidism. Although the analyses do not reflect all of the controversial nuances of the field, they do provide a means for a general approach to the study of glucose homeostasis and serve as a methodology that can be extrapolated to many areas of physiological study.
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PMID:Graphic analysis for the study of metabolic states. 871 58


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