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

When an endogenous morphine, beta-endorphin was discovered ten years ago, the fact that this morphine is present in the brain and many other tissues suggested to neurobiologists that these peptide opiates play a role which goes beyond that of a simple modulator of the perception of pain. beta-endorphin is a neurohormone which is secreted by the pituitary gland and reaches all tissues present in the body by diffusion. Many laboratories have investigated variations in serum levels of beta-endorphin under widely varying physiological or pathological conditions. Many references to these studies in the literature have thus demonstrated that beta-endorphins play a role in certain behavioural patterns (stress, alcoholism), in obesity, diabetes and psychiatric diseases. In fact, the activity of beta-endorphins would appear to have an interesting role to play and are a promising feature in the treatment of cerebral aging; in this field, beta-endorphins act not only as neuroregulators of other neurotransmitting substances but also, via calcium channels, exert an effect on the walls of cerebral arterioles. In situ, the role of beta-endorphins at the ionic channel level has been studied using the patch-clamp technique. In 1991, E Neher and B Sakmann received the Nobel Medicine and Physiology Prize for this work. beta-endorphin, which may be the "missing link" between the neuron and the wall of the arteriole, must be considered as being a fundamental neurotransmitter in the same way as well-known substances such as noradrenaline, acetylcholine, serotonin, dopamine and the GABAergic system are also neurotransmitters.
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PMID:Physiology of beta-endorphins. A close-up view and a review of the literature. 752 Feb 95

Left ventricular hypertrophy (LVH) is an early complication of hypertension. To a certain degree, this process counteracts the parietal stress induced by high blood pressure. Genetic factors, obesity, high salt diet and different growth factors, notably angiotensin II and noradrenaline, can also predispose to hypertrophic cardiomyopathy. Left ventricular mass is increased on echocardiography in about 20% of hypertensive subjects. LVH is initially associated with a change in myocardial diastolic function and later with abnormal systolic function. It is a major risk factor, a cause of cardiac failure, reduction in coronary reserve and of ventricular arrhythmias. Treatment of hypertension is associated with regression of LVH and preservation or improvement in myocardial diastolic and systolic functions. The decrease in left ventricular mass could reduce the incidence of cardiovascular complications in hypertension.
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PMID:[Physiopathology of left ventricular hypertrophy]. 764 13

Zucker lean and obese rats were injected under pentobarbital anesthesia with 125I-labeled insulin; at timed intervals from 30 to 120 sec, blood samples were extracted and used for the estimation of insulin levels by RIA. A group of rats from each series was maintained under a constant infusion of noradrenaline. For each insulin determination, a duplicate blood sample containing the same amount of insulin as that used in the RIA, but without the radioactive label, was used as a blank for insulin measurement. The radioactivity in these tubes was then used for the measurement of insulin label per ml blood. From plasma label decay curves and insulin concentrations, the insulin pool size, half-life, and rate of degradation were calculated. Obese rats had higher insulin levels (2.43 nM) and showed less effect of noradrenaline than their lean counterparts, in which insulin distribution volume shrank with noradrenaline treatment. The half-life of plasma insulin was similar in all groups (range, 226-314 sec). Pool size and overall degradation rates were higher in obese (198 femtokatals) than in lean rats (28 femtokatals). It is postulated that obese rats synthesize and cleave much more insulin than lean controls despite their higher circulating levels of insulin.
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PMID:Rat insulin turnover in vivo. 764 94

The discovery of the presynaptic histamine H3 receptors confirmed the idea that histamine is a neurotransmitter in the mammalian brain. The H3 receptors (autoreceptors) regulate the release and synthesis of histamine. The H3 receptors also modulate the other neurotransmitters (heteroreceptors). Subclasses of H3 antagonist binding sites were found in the brain (H3A and H3B). The regulation of noradrenaline release is reported to be mediated by H3A rather than H3B. The H3 binding site belongs to the class of receptors coupled to G-proteins. Besides the molecular data, this review focuses on the functional roles of H3 receptors in the brain and discusses the possible use of H3 ligands for neurobehavioral disorders. The pharmacological data of H3 ligands may provide clinical candidates for CNS disorders in which histamine plays important roles in mental and behavioral functions. Especially, H3 antagonists may be useful for CNS disorders such as narcolepsy, dementia, epilepsy, and obesity, while H3 agonists may provide for anxiety, insomnia, migraine. However, these suggestions are still preliminary and further clinical research is needed, although potent and safe novel H3 ligands are being developed.
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PMID:[Possible roles of brain histamine H3 receptors and the pharmacology of its ligands]. 779 25

Norepinephrine (NE) content and turnover rate, and the activity of dopamine-beta-hydroxylase (DBH) were measured in the brown adipose tissue (BAT) of developing Zucker rats of the three genotypes: Fa/Fa and Fa/fa (with a lean phenotype) and fa/fa (phenotypically obese). As early as 15 days of age, namely at a pre-obese stage, BAT NE content and turnover rate are already reduced in fa/fa rats, just like they are at 50 days. The development of DBH activity is completely impaired in fa/fa rats. These results demonstrate that the reduction in sympathetic tone in BAT of fa/fa rats is already present before the onset of phenotypic obesity.
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PMID:Decreased norepinephrine turnover rate in the brown adipose tissue of pre-obese fa/fa Zucker rats. 796

Upper-body obesity is an important risk factor for developing non-insulin dependent diabetes. To investigate the possibility that a lipolysis defect is present in this form of obesity, we examined the adrenergic regulation of lipolysis in abdominal subcutaneous fat cells from 25 women with upper-body obesity and 24 non-obese women. Lipolytic noradrenaline sensitivity (but not the maximum rate of lipolysis) was reduced by 10-fold in obese women (p < 0.01). The noradrenaline resistance could be ascribed to a 10-fold decrease in lipolytic beta 2-adrenoceptor sensitivity (p < 0.01). The lipolytic sensitivity of beta 1- and alpha 2-adrenergic receptors was normal in the obese women. A 70% reduction in the cell surface density of beta 2-adrenoceptors was observed compared to the control subjects (p < 0.01). However, beta 1-receptor density as well as steady-state mRNA levels for beta 1- and beta 2-receptors were normal in obese women. Lipolytic noradrenaline sensitivity correlated inversely with BMI (adjusted r2 = 0.76 together with fat cell volume in stepwise regression analysis). The fasting plasma level of free cortisol was 30% lower in obese compared to non-obese women (p < 0.05) but obesity did not influence resting plasma catecholamine levels. Thus, lipolytic catecholamine resistance is present in abdominal obesity, due to low density of beta 2-adrenoceptors, which in its turn may be caused by a post-transcriptional defect in beta 2-receptor expression.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Catecholamine resistance in fat cells of women with upper-body obesity due to decreased expression of beta 2-adrenoceptors. 774 23

Catecholamines are known to stimulate lipolysis of triglyceride stores in adipose tissue. However, the relationship of sympathoadrenal activity to serum lipid and lipoprotein concentrations remains uncertain. Since obesity, particularly the centripetal form, has recently been shown to be associated with increased urinary excretion of norepinephrine and decreased excretion of epinephrine, the possibility that the sympathoadrenal system is involved in the lipid abnormalities associated with the centripetal form of obesity was investigated. The relationship between 24-hour urinary catecholamine excretion and serum lipid and lipoprotein levels was examined among 615 male participants of the Normative Aging Study. Epinephrine excretion was positively correlated with the high-density lipoprotein cholesterol (HDL-C) level and the ratio of HDL-C to low-density lipoprotein cholesterol ([LDL-C] r = .15, P = .0002, and r = .11, P = .007, respectively) and inversely correlated with the triglyceride level (r = -.14, P = .0005). These relationships remained significant after adjusting for the effects of age, smoking, alcohol intake, adiposity, and insulin level. Epinephrine excretion was not significantly related to levels of total cholesterol or LDL-C. Norepinephrine and dopamine excretion were not significantly related to any lipid variable. These data suggest that (1) epinephrine plays an important role in regulating lipid and lipoprotein metabolism in humans, and (2) decreased adrenal medullary activity may contribute to the dyslipidemia (increased triglycerides and decreased HDL-C) commonly observed among the obese. The sympathoadrenal system therefore, along with hyperinsulinemia, may contribute to the increased cardiovascular risk associated with the insulin resistance syndrome.
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PMID:The relationship of epinephrine excretion to serum lipid levels: the Normative Aging Study. 815 12

Bearing in mind the importance of upper-body obesity for the insulin resistance (or metabolic) syndrome and the abnormalities in free fatty acid metabolism associated with this disorder, the regulation of lipolysis in isolated subcutaneous adipocytes was investigated in 13 72-yr old upper-body obese men with insulin resistance and glucose intolerance and in 10 healthy 72-yr-old men. There was a marked resistance to the lipolytic effect of noradrenaline in the metabolic syndrome due to defects at two different levels in the lipolytic cascade. First, an 80-fold decrease in sensitivity to the beta 2-selective agonist terbutaline (P < 0.001) which could be ascribed to a 50% reduced number of beta 2-receptors (P < 0.005) as determined with radioligand binding. The groups did not differ as regards dobutamine (beta 1) or clonidine (alpha-2) sensitivity, nor beta 1-receptor number. The mRNA levels for beta 1- and beta 2-receptors were similar in the two groups. Second, the maximum stimulated lipolytic rate was markedly reduced in the metabolic syndrome. This was true for isoprenaline (nonselective beta-agonist), forskolin (activating adenylyl cyclase), and dibutyryl cAMP (activating protein kinase). In regression analysis, the observed abnormalities in lipolysis regulation correlated in an independent way with the degree of glucose intolerance (r = -0.67) and beta 2-receptor number with insulin resistance (r = 0.67). In conclusion, the results of this study indicate the existence of lipolytic resistance to catecholamines in the adipose tissue of elderly men with the metabolic syndrome, which may be of importance for impaired insulin action and glucose intolerance. The resistance is located at a posttranscriptional level of beta 2-receptor expression and at the protein kinase-hormone sensitive lipase level.
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PMID:Multiple lipolysis defects in the insulin resistance (metabolic) syndrome. 820 Sep 97

The effects of norepinephrine and insulin on glucose transport were investigated in brown adipocytes isolated from obese nondiabetic Lister and Albany (LA/N-cp strain) rats (O-LA), obese diabetic spontaneously hypertensive (SHR/N-cp strain) rats (O-SHR), and from their lean (L) controls to test whether the decreased calorigenic response to norepinephrine of O-SHR adipocytes was specifically associated with alterations in glucose metabolism. Norepinephrine and insulin independently stimulated glucose transport in L-LA, O-LA, and L-SHR brown adipocytes, but their stimulatory effects were markedly reduced in O-SHR cells. Both insulin responsiveness and the total number of insulin receptors were significantly decreased in O-SHR adipocytes but not in O-LA cells. The number of high-affinity beta 1/beta 2-adrenoceptors was significantly increased (+70%) in O-LA adipocytes but was similar in L-SHR and O-SHR cells. These results indicate that 1) major metabolic defects are present in brown adipose tissue (BAT) of O-SHR but not of O-LA, although these two strains are homozygous for the cp allele, 2) postreceptor defects are predominantly involved in O-SHR adipocyte refractoriness to norepinephrine, and 3) a reduced mitochondrial content may represent the principal metabolic alteration explaining the decreased effects of norepinephrine on both thermogenesis and glucose transport. It is postulated that the marked insulin resistance of O-SHR leads to a decreased mitochondriogenesis in BAT, resulting in a diminished tissue thermogenic capacity and reduced glucose metabolism, thereby contributing to obesity and diabetes.
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PMID:Norepinephrine- and insulin-resistant glucose transport in brown adipocytes from diabetic SHR/N-cp rats. 821 49

In order to understand the relationship between patients' adrenal function and simple obesity and effect of acupuncture on it, the obesity indices, lipid indices, fasting blood-glucose, noradrenaline, dopamine, adrenalin and cortisol were observed. The results indicated that patients with simple obesity had hypofunction of the sympathetic-adrenal system and the hypothalamus-pituitary-adrenal system. Acupuncture treatment not only affected weight loss but also enhanced functioning of the two systems, suggesting that the effect of acupuncture on weight loss may be produced by enhancing the functions of both the sympathetic-adrenal system and the hypothalamus-pituitary-adrenal system.
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PMID:Effect of acupuncture on weight loss evaluated by adrenal function. 824 84


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