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

It is well known that in pre-menopausal women the incidence of cardiovascular events is lower than in men of the same age and that after the menopause cardiovascular morbidity and mortality in women become similar, if not higher, than that in men indicating that female sex hormones play a relevant protective role upon the vasculature. Among the cardiovascular risk factors, hypertension appears to be more prevalent in postmenopausal women than in men but the precise mechanism through which menopause favours the development of hypertension is still a matter of debate. The prevalence of obesity and being overweight is also higher in postmenopausal women than that in men of comparable age. The pathogenesis of obesity-related hypertension recognizes a multifactorial mechanism including overactivity of the sympathetic nervous system, insulin resistance, leptin resistance, overactivity of the renin-angiotensin-aldosterone system and, finally, a blunted biological activity of the natriuretic peptides. The latter mechanism has been investigated by our group in recent years. Adipose tissue has been shown to express large amounts of mRNA for the biologically inactive C-type natriuretic peptide receptor (NPr-C) and this expression is decreased by fasting. Accordingly, adipose tissue can participate in the development and maintenance of high blood pressure through a reduced bioavailability of circulating natriuretic peptides leading to sodium retention. Since being overweight and obesity are a common finding in postmenopausal women, the complex mechanism of obesity-related hypertension can play a relevant role in explaining the high prevalence of hypertension after the menopause.
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PMID:Hypertension and obesity after the menopause. 1218 46

The major side effects due to estrogens in oral contraceptives are summarized, (thromboembolism, hypertension, diabetes, lipid metabolism, liver function) 2 retrospective studies on thromboembolism are reviewed. Estrogens decrease bile flux in the liver, which can become manifest as jaundice or pruritus, and may be the cause of abnormal synthesis of proteins by the liver. Glucose tolerance decreases and insulinemia rises in 30% of users after 2 years and in 80% after 5 years, often revealing latent diabetes or causing obesity. Plasma fatty acids and triglycerides increase, and in the predisposed, hyperlipidemia may appear. Hypercoagulability results from increased synthesis of clotting factors by the liver and thromboembolism may become more likely because of hypertension, obesity and lesions in the veins. Hypertension seems due to increased output of angiotensinogen by the liver and aldosterone by the adrenal. A British retrospective study on less than 10% of known thromboembolism cases implicates estrogen doses above 50 mcg, but found several contradictions.
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PMID:[Are estrogens responsible for incidents observed under combined estrogen-progestagen treatment?]. 1230 14

Based on the clinical observation that humans with visceral adiposity have higher plasma aldosterone levels than controls, we postulated that endogenous fatty acids can be oxidized by the liver to form stimuli of the adrenal cortex. Although we could show that hepatocytes produced adrenal stimuli from linoleic acid in vitro, the yield was very small. To facilitate the elucidation of chemical structures, we incubated a large amount of linoleic acid with lipoxygenase, then treated the hydroperoxide with cysteine and iron. The major product of this process was 12,13-epoxy-9-keto-10-trans-octadecenoic acid. This epoxy-keto compound stimulated aldosterone production at concentrations from 0.5 to 15 microm. At higher concentrations, it was inhibitory. The epoxy-keto-octadecenoic acid exhibited the chromatographic characteristics of one product of the incubation of linoleic acid with hepatocytes. The results are consistent with the postulated conversion of linoleic acid to stimuli of aldosterone production. This may be a mechanistic link between visceral obesity and hypertension in humans.
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PMID:An oxidized derivative of linoleic acid affects aldosterone secretion by adrenal cells in vitro. 1232 36

The chemical diversity of estrogen and progestogen components of oral contraceptive (OC) products, their use alone or in combination, and the diversity of treatment regimens and doses account for the majority of contradictions in the immense literature on vascular and metabolic side effects of these hormones. OCs are exclusively composed of synthetic hormones. All OCs impose metabolic modifications on the organism and especially on the hepatic parenchyma due to delayed hepatic degradation. Certain factors increase the risk of vascular accidents associated with OC use: metabolic changes affecting coagulation, lipids, glucides, and arterial hypertension, immunologic phenomena, smoking, and obesity. As a whole, OCs affect coagulation by elevating factors 7 and 10, decreasing antithrombin iii (in high doses), and decreasing plasma fibrinolytic activity. synthetic estrogens cause an elevation of HDL cholesterol, a slight elevation of phospholipids, and a dose-dependent elevation of triglycerides and their VLDL fraction. As a group, progestogens tend to decrease the HDL fraction of cholesterol. Norethindrone is incapable of opposing the hypertriglyceridemic action of synthtic estrogens, while norgestrel partially opposes it. Lipid modifications provoked by combined OCs are a function of the nature and dosage of the components. Among hemodynamic modifications, synthetic estrogens cause elevations in renin substrate, plasma renin activity, angiotensin 2 and aldosterone. Synthetic progestogens may have various effects depending on type and dose, but they do not appear sufficient to cause hypertension unless other factors linked to individual predispositions are present. Microdoses of progestogens alone do not affect the renin-angiotensin-aldosterone system. Studies have also been conducted on the effect of OCs on cardiac function and on the vascular walls. Prospective studies suggest a relative risk of 3 for venous thromboembolic accidents among OC users, while retrospective studies suggest a relative risk of 4-11. Thromboembolic risk is directly correlated with the dose of synthetic estrogens. Recent studies indicate a relative risk of 3-5 for myocardial infarct and cerebral vascular accidents in OC users. Most studies have indicated a multiplier effect of OCs on preexisting risk factors, especially age and smoking. Prevention of vascular accidents is based on the prescription of smaller doses and careful observation of absolute and relative contraindications to OC use.
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PMID:[Sex steroids and vascular risk]. 1233 12

Bilateral adrenalectomy (ADX) either prevents or attenuates obesity in several animal models. Mice that express an antisense RNA to the glucocorticoid receptor (GCR) are obese. The present study was conducted to examine the effects of ADX and aldosterone (ALDO) replacement on the rate of weight gain and body composition of mice bearing an antisense GCR gene construct. Twenty-eight male transgenic mice bearing the antisense GCR construct and 16 male B6C/3F1 mice were either bilaterally ADX or given sham operations. At the time of surgery, some of the ADX mice and all of the sham-operated mice were implanted with 100-mg cholesterol (CHOL) pellets inserted subcutaneously in the subscapular region. The remaining ADX mice were implanted with 100-mg 1% w/w ALDO pellets using CHOL as vehicle. All mice were returned to their home cages for 2 weeks. They were then decapitated and the blood was collected for corticosterone, ALDO, insulin, and leptin radioimmunoassay. Carcasses were eviscerated and prepared for gravimetric analyses, including bomb calorimetry. ADX resulted in a significant drop in carcass fat in both transgenic and wildtype groups. ALDO prevented the decrease in carcass fat in both groups. Two weeks after ADX, transgenic mice were as fat as sham-operated wildtype controls, whereas both sham-operated and ALDO-treated transgenic groups were significantly fatter. Despite observing a reliable decrease in carcass fat following ADX, no corresponding decrease in circulating leptin was found.
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PMID:The effects of adrenalectomy and aldosterone replacement in transgenic mice expressing antisense RNA to the type 2 glucocorticoid receptor. 1241 18

Diabetes mellitus increases the risk for hypertension and associated cardiovascular diseases, including coronary, cerebrovascular, renal and peripheral vascular disease. The risk for developing cardiovascular disease is increased when both diabetes and hypertension co-exist; in fact, over 11 million Americans have both diabetes and hypertension. These numbers will continue to climb, internationally, since the leading associated risk for diabetes development, obesity, has reached epidemic proportions, globally. Moreover, the frequent association of diabetes with dyslipidemia, as well as coagulation, endothelial, and metabolic abnormalities also aggravates the underlying vascular disease process in patients who possess these comorbid conditions. The renin-angiotensin-aldosterone system (RAS) and arginine vasopressin (AVP) are overactivated in both hypertension and diabetes. Drugs that inhibit this system, such as ACE inhibitors and more recently angiotensin receptor antagonists (ARBs), have proven beneficial effects on the micro- and macrovascular complications of diabetes, especially the kidney. The BRILLIANT study showed that lisinopril reduces microalbuminuria better than CCB therapy. Numerous other long-term studies confirm this association with ACE inhibitors including the HOPE trial. Furthermore, the European Controlled trial of Lisinopril in Insulin-dependent Diabetes (EUCLID) study, showed that lisinopril slowed the progression of renal disease, even in individuals with mild albuminuria. In fact, there are now five appropriately powered randomized placebo-controlled trials to show that both ACE inhibitors and ARBs slow progression of diabetic nephropathy in people with type 2 diabetes. These effects were shown to be better than conventional blood pressure lowering therapy, including dihydropyridine CCBs. In patients with microalbuminuria, ACE inhibitors and ARBs reduce the progression of microalbuminuria to proteinuria and provide a risk reduction of between 38 and 60% for progression to proteinuria. This is important since microalbuminuria is known to be associated with increased vascular permeability and decreased responsiveness to vasodilatory stimuli. Recently, increased AVP levels have been lined to microalbuminuria and hyperfiltration in diabetes. The microvascular and macrovascular benefits of ACE inhibition, ARBs and possible role of AVP antagonists in diabetic patients will be discussed, as will be recommendations for its clinical use.
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PMID:Treatment of the diabetic patient: focus on cardiovascular and renal risk reduction. 1243 44

Adrenal steroidogenesis is under complex control, and clinical observations suggest that not all regulators have been identified. We postulated that fatty acid oxidation products found in the diet or formed in the body could affect steroidogenesis. Linoleic acid is a prominent constituent of animal fat and is readily oxidized. We found that several products of linoleic acid oxidation affect production of aldosterone and corticosterone by isolated cells from rat adrenals. We characterized one linoleic acid derivative by gas chromatography/mass spectrometry. It is 12,13-epoxy-9-oxo-10(trans)-octadecenoic acid ("EKODE"). At concentrations between 1 and 30 microM, EKODE stimulated production of aldosterone by zona glomerulosa cells, but at concentrations above 50 microM, it was inhibitory. In zona fasciculata cells, EKODE stimulated corticosterone production at concentrations of 5 microM or greater, and there was no evidence of inhibition at high concentrations. Stimulation of steroidogenesis was observed after 15 min of incubation and continued for at least 2 hrs. The potential relevance of our findings to the hypertension of obesity is discussed.
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PMID:Oxidized products of linoleic acid stimulate adrenal steroidogenesis. 1253 Jun 33

Renin-angiotensin-aldosterone system (RAAS) blockade with angiotensin-converting enzyme inhibitors (ACE-I) or angiotensin II (Ang II), AT(1)-receptor blockers (ARB) is the cornerstone of renoprotective therapy. Still, the number of patients with end-stage renal disease is increasing worldwide, prompting the search for improved renoprotective strategies. In spite of proven efficacy at group level, the long-term renoprotective effect of RAAS blockade displays a marked between-patient heterogeneity, which is closely linked to between-patient differences in the intermediate parameters of blood pressure, proteinuria and renal haemodynamics. Of note, the between-patient differences by far exceed the between-regimen differences, and thus may provide a novel target for exploration and intervention. The responsiveness to RAAS blockade appears to be an individual characteristic as demonstrated by studies applying a rotation-schedule design. The type and severity of renal disease, obesity, insulin-resistance, glycaemic control, and genetic factors may all be involved in individual differences in responsiveness, as well as dietary factors, such as dietary sodium and protein intake. Several strategies, such as dietary sodium restriction and diuretic therapy, dose-titration for proteinuria, and dual RAAS blockade with ACE-I and ARB, can improve the response to therapy at a group level. However, when analysed for their effect in individuals, it appears that these measures do not allow poor responders to catch up with the good responders, i.e. in spite of their efficacy at group level, the available measures are usually not sufficient to overcome individual resistance to RAAS blockade. We conclude that between-patient differences in responsiveness to renoprotective intervention should get specific attention as a target for intervention. Unravelling of the underlying mechanisms may allow development of specific intervention. Based on the currently available data, we propose that response-based treatment schedules, with a multidrug approach titrated and adapted at individual responses rather than fixed treatment schedules, may provide a fruitful strategy for more effective renoprotection.
J Renin Angiotensin Aldosterone Syst 2002 Dec
PMID:Between-patient differences in the renal response to renin-angiotensin system intervention: clue to optimising renoprotective therapy? 1258 64

In order to investigate the contribution of candidate genes in the renin-angiotensin-aldosterone system (RAAS) in pathogenesis of essential arterial hypertension (EAH), the I/D polymorphism of ACE gene, the M235T polymorphism of the angiotensinogen gene, and the angiotensin II type 1 receptor (AGT,R) A1166C gene polymorphism in a group of children with EAH were analyzed. Fifty-scven children, aged 8-19 years. with the diagnosis of EAH were included in the association study and were compared with 57 subjects with normal blood pressure (the control group). Arterial hypertension was defined as systolic/diastolic blood pressure measurements higher than 95 age-gender-height percentile of the adopted reference values. A trend was found towards an association between the M235T angiotensinogen gene polymorphism and EAH in childhood in a dominant model (odds ratio (OR) 2.1; 95% confidence interval (CI) 0.9-5.1; P = 0.077), whereas the authors failed to demonstrate an association between the ACE I/D gene polymorphism, or the A1166C AGT1R gene polymorphism and EAH in childhood. Additionally, evidence was found of interaction between the angiotensinogen-TT genotype and obesity on the risk of EAH in childhood (OR 19.3; 95% CI 1.1-77.3; P = 0.014). In conclusion, the M235T angiotensinogen gene polymorphism is considered alone as well as in interaction with obesity to be risk factors for EAH in childhood.
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PMID:Gene polymorphisms of the renin-angiotensin-aldosterone system and essential arterial hypertension in childhood. 1259 35

To elucidate the role of leptin in regulating neuroendocrine and metabolic function during an acute fast, six to eight healthy, lean men were studied under four separate conditions: a baseline fed state and three 72-hour fasting studies with administration of either placebo, low-dose recombinant-methionyl human leptin (r-metHuLeptin), or replacement-dose r-metHuLeptin designed to maintain serum leptin at levels similar to those in the fed state. Replacement-dose r-metHuLeptin administered during fasting prevents the starvation-induced changes in the hypothalamic-pituitary-gonadal axis and, in part, the hypothalamic-pituitary-thyroid axis and IGF-1 binding capacity in serum. Thus, in normal men, the fall in leptin with fasting may be both necessary and sufficient for the physiologic adaptations of these axes, which require leptin levels above a certain threshold for activation. In contrast to findings in mice, fasting-induced changes in the hypothalamic-pituitary-adrenal, renin-aldosterone, and growth hormone-IGF-1 axes as well as fuel utilization may be independent of leptin in humans. The role of leptin in normalizing several starvation-induced neuroendocrine changes may have important implications for the pathophysiology and treatment of eating disorders and obesity.
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PMID:The role of falling leptin levels in the neuroendocrine and metabolic adaptation to short-term starvation in healthy men. 1272 33


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