Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0028754 (obesity)
 124,988 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The past 10-15 years have produced a significant increase in knowledge and theories concerning the regulation of energy balance, but the precision of this regulation is still uncertain. However, the fact that investigators have had to resort to a variety of techniques and ploys (some of them bizarre) to produce marked pertubations in body weight is in itself an indication that the regulatory system can be very robust. Although control of food intake obviously plays a major role in this system, control of energy expenditure (i.e. DIT) also has to be considered as an important factor in the maintenance of energy balance. In this review most of the evidence for DIT and its biochemical origins has been derived from studies on experimental animals. Many of the overfeeding studies carried out on man are consistent with the animal work, but because of differences in interpretation and some equivocal results, the role of DIT in human metabolism is still a contentious issue. This problem may not be fully resolved to everyone's satisfaction until complete, continuous, and very precise energy balance measurements are made on chronically overfed lean subjects. Before this expensive and arduous experiment is undertaken, evidence for thermogenesis in man will continue to depend on acute measurements of the metabolic response to various stimuli. An increasing number of studies (e.g. 35, 80) have demonstrated the existence of NST in man, and the possibility that this could originate from BAT is supported by histological (62, 148) and thermographic data (130). Conversely, reductions in cold tolerance (2, 18) and thermogenic responses to noradrenaline (82) with increasing adiposity are similar to the blunted responses seen in genetically obese animals, which suggests that human obesity may also involve an impairment in thermogenesis. At the present time these ideas concerning the important of DIT in man and its role in obesity remain somewhat speculative, but no doubt this area will now be the subject of further research. Similarly, the impact of early nutritional influences on subsequent energy balance regulation and resistance to obesity will receive more attention following the report (144) that hyperphagia in rats during early life results in a reduced body fat content and leanness in adulthood. The relative contributions and interactions between intake and output in energy balance need clarifying, and in terms of central organization, the mechanisms of appetite control should now be considered for their relevance to the control of thermogenesis.(ABSTRACT TRUNCATED AT 400 WORDS)
 ...
PMID:Regulation of energy balance. 676 16

Several studies have suggested that obese subjects have a reduced thermic effect of feeding when compared to normal weight controls. The present study was undertaken to further define this apparent abnormality, and evaluate the role of norepinephrine in the thermic response to food. A test formula meal of 800 calories (85% carbohydrate, 15% protein) was taken by 7 control and 6 moderately obese subjects whose obesity was adult in onset. The rise in resting oxygen consumption following the test meal was greater in the control than in the obese group (p less than 0.01), and there was a significant inverse correlation between the relative degree of obesity and this response to feeding (r = -0.59, p less than 0.05). Norepinephrine concentrations were greater in the obese than in the control group both before (p less than 0.05) and after (p less than 0.05) feeding. No correlations were found between the plasma norepinephrine concentrations and the rise in oxygen consumption after feeding. Four of the 6 obese subjects were restudied after weight reduction. The reduced-obese group showed a trend toward normalization of basal measurements and responses to feeding. It is concluded that the reduced thermic response to feeding seen in the obese subjects studied cannot be directly accounted for by diminished sympathetic nervous system activity as reflected by plasma levels of norepinephrine.
 ...
PMID:Reduced thermic effect of feeding in obesity: role of norepinephrine. 682 82

Discrete, bilateral, radiofrequency destruction of the ventral noradrenergic bundle (VB) resulted in a pronounced fall in levels of noradrenaline in the hypothalamus but not in the cortex. On days 4 and 12, but not 28, post-surgery, VB-lesioned rats were hyperactive (rearing and ambulation) upon exposure to a novel open-field space. This hyperactivity was greatly attenuated by naloxone, which did not significantly modify sham activity. These data suggest that the VB may be involved in the control of locomotor-exploratory activity via an interaction with an endorphinergic system. On day 4, but not 12 or 25, VB-lesioned rats displayed a significant elevation in core temperature (Tc). No difference in the hyperthermia elicited by introduction into the open-field was, however, seen between VB-lesioned and sham rats on day 4. In both groups, this rise in Tc was strongly attenuated by naloxone. These data indicate that the VB may be involved in the control of Tc but that it does not mediate novelty-stress evoked hyperthermia, for which endorphins are primarily responsible. Within 7 days post-surgery, VB-lesioned rats developed an enhancement of daily food intake which led to a slight obesity. From day 15 onward, a hyperdipsia was also seen in VB-lesioned rats. Naltrexone reduced the food and water intake of both sham and VB-lesioned animals but failed to totally block this hyperphagia. It is suggested that the VB is involved in the regulation of daily ingestive behaviour and that endorphins do not exclusively mediate the VB-lesion induced hyperphagia.
 ...
PMID:The role of the ventral noradrenergic bundle in relation to endorphins in the control of core temperature, open-field and ingestive behaviour in the rat. 683 76

1. The thermogenic response and changes in plasma substrates and hormones were tested after a liquid meal in lean, obese and formerly obese women. 2. Subjects with a family history of obesity tested either while obese or after slimming to a normal weight had a thermogenic response, which was only half that of the lean group. 3. The immediate response in plasma glucose and insulin was greater in the lean subjects, but the sustained changes in circulating substrates did not differ in the three groups. Thyroidal hormone concentrations did not alter postprandially: venous noradrenaline levels rose in the obese groups only. 4. The differences in postprandial thermogenesis at rest would reduce the energy requirements of subjects with familial obesity, but they still had a metabolic rate estimated to be nearly 1MJ (240 kcal)/day in excess of the lean group so additional thermogenic defects must exist for familial obesity to be explained solely on a metabolic basis.
 ...
PMID:Postprandial thermogenesis in obesity. 701 1

1. The metabolic response of lean and obese women to caffeine was studied to see if caffeine could be used to demonstrate the subnormal thermogenesis in obesity previously shown after standard meals or intravenous infusions of noradrenaline. 2. The rise in resting metabolic rate with caffeine was similar in the lean and obese groups and beta-adrenoceptor blockade did not reduce the increment in metabolic rate in either group. These responses did not, therefore, correspond with the other subnormal thermogenic responses of the constitutionally obese. 3. In a post-obese group, i.e. previously obese women who were now of normal weight, there was a reduced response of the resting metabolic rate to caffeine. 4. Monitoring plasma substrate concentrations showed that the change in oxygen uptake corresponded to changes in plasma free fatty acids, so that in adults the metabolic effects of caffeine seem to be mediated by increases in adipocyte lipolysis. This effect seems to be mainly independent of the adrenergic system.
 ...
PMID:Caffeine: its effect on catecholamines and metabolism in lean and obese humans. 701 2

The antilipolytic effect of insulin in vitro was investigated in conditions known to be associated with resistance to the effect of insulin on glucose metabolism. Human subcutaneous adipose tissue was obtained from 14 obese subjects before and during starvation for 7 days, 12 untreated non-insulin dependent diabetics (NIDDM), 6 untreated insulin dependent diabetics (IDDM), and 10 nonobese control subjects. The tissue was incubated with and without insulin in concentration ranging from 1-10,000 microunits/ml. Responsiveness (maximum effect) and sensitivity to insulin were determined under basal induction conditions, since insulin had a bimodal effect on noradrenaline stimulated lipolysis. Under normal conditions both insulin sensitivity and insulin responsiveness were positively correlated with the basal rate of lipolysis. In obesity, IDDM and NIDDM there were no change in insulin sensitivity or in insulin responsiveness. When the obese subjects were divided into one hyperinsulinemic group (6 individuals) and one group with normal fasting serum insulin levels (7 individuals) a similar antilipolytic effect of insulin was observed in the two groups. During starvation there was a 20-fold increase in insulin sensitivity (p less than 0.01) but no change in insulin responsiveness in femoral fat and only a decrease in responsiveness (p less than 0.01) in abdominal fat. The present data supports the view that antilipolysis in human fat cells is not involved in the insulin resistance seen in obesity, starvation, diabetes and hyperinsulinemia.
 ...
PMID:The antilipolytic effect of insulin in human adipose tissue in obesity, diabetes mellitus, hyperinsulinemia, and starvation. 702 6

Body composition, glucose metabolism and indices of sympathetic nervous activity were studied in two different samples of unselected normotensive and hypertensive middle-aged men. The hypertensive subjects were more often obese and had more often an impaired glucose tolerance and a higher fasting insulin compared with the normotensives. The metabolic differences were not explained simply by the higher degree of obesity in the hypertensives, but seemed also to be related to an increased excretion of noradrenaline, ie to an increased overall sympathetic activity. The impaired glucose metabolism might be one of the factors explaining the variable prognosis in essential hypertension.
 ...
PMID:Body composition, metabolic and hormonal characteristics in unselected male hypertensives. 723 71

Evidence from animals models of obesity, eg the ob/ob mouse, and from studies in man are consistent with the autonomic regulation of brown tissue being one of the principal pathways involved in the normal thermogenic regulation of energy balance. Studies in man on other components of the sympathetic nervous system do not suggest generalized autonomic abnormalities in obese patients. Patients placed on a reduced carbohydrate intake show a fall in metabolic rate, a reduction in cardiovascular indices of sympathetic activity and a fall in venous noradrenaline concentrations. The hypotensive effect is accompanied by a precipitous fall in hydroxy-methoxymandelic acid excretion. These changes are not nearly so evident in those obese patients who are also hypertensive so there may be altered control of catecholamine metabolism in obese hypertensive patients.
 ...
PMID:Autonomic responsiveness in obesity with and without hypertension. 723 75

Lean and genetically obese (ob/ob): mice were treated daily for 2 wk with thyroxine (T4), noradrenaline, or thyroxine plus noradrenaline. T4 treatment of obese mice increased the abnormally low binding of GDP to brown adipose tissue mitochondria and permitted a cold-induced increase to occur. It also brought about a return to a more normal ultrastructure of the mitochondria of the obese mice. T4 treatment did not alter the binding of GDP to brown adipose tissue mitochondria of lean mice. The binding of GDP to brown adipose tissue mitochondria is known to be to a 32,000-dalton polypeptide associated with the thermogenic proton conductance pathway. T4 treatment did not alter the proportion of this polypeptide in the mitochondrial membrane in either lean or obese mice. Treatment with noradrenaline did not alter the binding of GDP to brown adipose tissue mitochondria in either lean or obese mice. The effect of T4 is thought to be due to an improvement in the defective responsiveness of brown adipose tissue to endogenous noradrenaline in the obese mice, known to be related to their poor cold resistance and obesity. The improvement allows a more normal noradrenaline-induced unmasking of GDP binding sites, both in response to diet and in response to cold. Such treatment is known to improve cold resistance of the obese mice, and this appears to be correlated with an improvement in the functioning of their defective brown adipose tissue.
 ...
PMID:Abnormal brown adipose tissue in genetically obese mice (ob/ob): effect of thyroxine. 732 26

Obese subjects are at an increased risk of becoming hypertensive and vice versa. Essential hypertension and obesity are commonly accompanied by insulin resistance (defined as impaired insulin-mediated glucose disposal) and hyperinsulinaemia. In the offspring of patients with essential hypertension, insulin resistance and hyperinsulinaemia, as well as related increases in serum low density lipoproteins and triglycerides, often occur prior to the development of essential hypertension, overweight or central redistribution of body fat. Moreover, once obesity, and in particular central obesity, is present, insulin resistance is more marked in hypertensive than in normotensive obese subjects. Hyperinsulinaemia and/or insulin resistance in turn promote body fat deposition and impaired glucose tolerance. This cycle helps to explain why a familial predisposition to essential hypertension poses an increased risk of developing not only hypertension but also dyslipidaemia, obesity and non-insulin-dependent (type 2) diabetes. It is still unclear whether insulin resistance and/or hyperinsulinaemia also promote hypertension per se. Regardless of insulin's exact pathogenic role, obesity and/or a high dietary intake of carbohydrates, salt, etc. can induce several potential pressor mechanisms: 1) higher plasma noradrenaline (norepinephrine) and adrenaline (epinephrine) levels, suggesting a higher sympathetic tone in obese than in nonobese subjects, and in hypertensive obese than in normotensive obese subjects; 2) similarly, a tendency to hyperaldosteronism, with largely normal plasma renin activity, in obese hypertensive patients; 3) enhanced sensitivity of blood pressure to salt; 4) increased total blood volume (although it is normal relative to body surface area), leading to increased cardiac output and eventually eccentric left ventricular hypertrophy; and 5) increased cytosolic free Ca++ levels and reduced intracellular Mg++ levels in the blood cells of obese hypertensive patients and patients with non-insulin-dependent diabetes, although this finding cannot necessarily be extrapolated to cationic levels in vascular muscle cells. Total peripheral vascular resistance is usually low in normotensive obese subjects and rises with the development of hypertension; compared with lean patients with essential hypertension, obese hypertensive patients tend to have a slightly lower level of total peripheral vasoconstriction and a slightly higher cardiac output. Considering the intimate association between essential hypertension and obesity, as well as the prevalence and prognostic relevance of this combination, the spectrum of accompanying metabolic and cardiovascular abnormalities deserves careful consideration in the evaluation of therapeutic care for such patients.
 ...
PMID:The pathogenesis of hypertension in obese subjects. 751 75


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>