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

Obesity may account for as much as 65% to 75% of human essential hypertension in most industrialized countries. Excess renal sodium reabsorption and a hypertensive shift of renal-pressure natriuresis play a key role in mediating obesity hypertension. Sympathetic activation contributes to obesity-induced sodium retention and hypertension because adrenergic blockade or renal denervation markedly attenuates these changes. Recent observations suggest that leptin and its multiple interactions with other neurochemical pathways in the hypothalamus may be a partial link between excess weight gain and increased sympathetic activity. Short-term administration of leptin into the cerebral ventricles increases renal sympathetic activity, and long-term intravenous leptin infusions in nonobese rodents at rates that raise plasma concentrations to the levels found in severe obesity increase arterial pressure and heart rate through adrenergic activation. Also, transgenic mice that overexpress leptin develop hypertension. Acute studies suggest that the renal sympathetic effects of leptin may depend on interactions with other neurochemical pathways in the hypothalamus, including melanocortin-4 receptors. However, it is unclear whether this pathway or others, such as neuropeptide Y, mediate the long-term effects of leptin on blood pressure. In addition, leptin has other actions, such as stimulation of nitric oxide formation and enhancement of insulin sensitivity, which may tend to reduce blood pressure in some conditions. Although the precise role of these complex interactions in human obesity has not been elucidated, this is an important area for further investigation, especially considering the current epidemic of obesity in most industrialized countries.
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PMID:Obesity hypertension: role of leptin and sympathetic nervous system. 1141 45

Obesity is associated with insulin resistance and some reproductive abnormalities. Circulating FFAs are often elevated in obese subjects and are also closely linked to insulin resistance. In this study, we demonstrated that saturated FFAs, such as palmitic acid and stearic acid, markedly suppressed the granulosa cell survival in a time- and dose-dependent manner. Polyunsaturated FFA, arachidonic acid, had no effect on the cell survival, even at supraphysiological concentrations. The suppressive effect of saturated FFAs on cell survival was caused by apoptosis, as evidenced by DNA ladder formation and annexin V-EGFP/propidium iodide staining of the cells. The apoptotic effects of palmitic acid and stearic acid were unrelated to the increase of ceramide generation or nitric oxide production and were also completely blocked by Triacsin C, an inhibitor of acylcoenzyme A synthetase. In addition, acylcoenzyme A, pamitoylcoenzyme A, and stearylcoenzyme A markedly suppressed granulosa cell survival, whereas arachidonoylcoenzyme A had no such effect, and this finding was consistent with the effect of the respective FFA form. Surprisingly, arachidonic acid instead showed a protective effect on palmitic acid- and stearic acid-induced cell apoptosis. A Western blot analysis showed the apoptosis of the granulosa cells induced by palmitic acid to be accompanied by the down-regulation of an apoptosis inhibitor, Bcl-2, and the up-regulation of an apoptosis effector, Bax. These results indicate that saturated FFAs induce apoptosis in human granulosa cells caused by the metabolism of the respective acylcoenzyme A form, and the actual composition of circulating FFAs may thus play a critical role in the apoptotic events of human granulosa cells. These effects of FFAs on granulosa cell survival may be a possible mechanism for reproductive abnormalities, such as amenorrhea, which is frequently observed in obese women.
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PMID:Saturated FFAs, palmitic acid and stearic acid, induce apoptosis in human granulosa cells. 1145 7

Studies in Zucker diabetic fatty rats have led to the concept that chronically elevated free fatty acid (FFA) levels can cause apoptosis of triglyceride-laden pancreatic beta-cells as a result of the formation of ceramides, which induce nitric oxide (NO)-dependent cell death. This "lipotoxicity" hypothesis could explain development of type 2 diabetes in obesity. The present study examines whether prolonged exposure to FFA affects survival of isolated normal rat beta-cells and whether the outcome is related to the occurrence of triglyceride accumulation. A dose-dependent cytotoxicity was detected at 5-100 nmol/l of unbound oleate and palmitate, with necrosis occurring within 48 h and an additional apoptosis during the subsequent 6 days of culture. At equimolar concentrations, the cytotoxicity of palmitate was higher than that of oleate but lower than that of its nonmetabolized analog bromopalmitate. FFA cytotoxicity was not suppressed by etomoxir (an inhibitor of mitochondrial carnitine palmitoyltransferase I) or by antioxidants; it was not associated with inducible NO synthase expression or NO formation. An inverse correlation was observed between the percentage of dead beta-cells on day 8 and their cellular triglyceride content on day 2. For equimolar concentrations of the tested FFA, oleate caused the lowest beta-cell toxicity and the highest cytoplasmic triglyceride accumulation. On the other hand, oleate exerted the highest toxicity in islet non-beta-cells, where no FFA-induced triglyceride accumulation was detected. In conditions without triglyceride accumulation, the lower FFA concentrations caused primarily apoptosis, both in islet beta-cells and non-beta-cells. It is concluded that FFAs can cause death of normal rat islet cells through an NO-independent mechanism. The ability of normal beta-cells to form and accumulate cytoplasmic triglycerides might serve as a cytoprotective mechanism against FFA-induced apoptosis by preventing a cellular rise in toxic free fatty acyl moieties. It is conceivable that this potential is lost or insufficient in cells with a prolonged triglyceride accumulation as may occur in vivo.
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PMID:Inverse relationship between cytotoxicity of free fatty acids in pancreatic islet cells and cellular triglyceride accumulation. 1147 37

To examine the role of nitric oxide (NO) on thermoregulation and control of breathing in obesity, awake obese and age-matched lean Zucker (Z) rats underwent a sustained hypoxic challenge. Body temperature (Tb), oxygen consumption (V O(2)) and ventilation (V E) were measured during room air and during 30-min of hypoxia (10% O(2)) after intraperitoneal administration of either 100 mg/kg of N(G)-nitro-L-arginine methyl ester (L-NAME), a nonspecific NOS inhibitor, 25 mg/kg of 7-nitroindazole (7-NI), a selective neuronal NOS inhibitor, or equal volume of vehicle (dimethyl sulfoxide: DMSO) as control. Tb in obese rats during room air was significantly lower than that of lean rats. Hypoxia induced a more pronounced drop in Tb and V O(2) in lean rats than in obese rats. Tb in lean Z rats dropped significantly by approximately 0.2 degrees C after L-NAME and, more markedly, by approximately 1.1 degrees C after 7-NI compared with control during room air, whereas Tb in obese Z rats was unaffected. L-NAME and 7-NI attenuated hypoxia-induced hypothermia or hypometabolism in lean rats, but not in obese rats. Lean rats exhibited an abrupt increase in V E in response to hypoxia followed by a gradual decline in V E. In contrast, obese rats displayed an initial increase in V E that plateaued during sustained hypoxia. Both L-NAME and 7-NI induced marked decreases in V E during room air and hypoxia compared with control lean rats, whereas V E was virtually unaffected by either agent in obese rats. The present results suggest that the blunted thermoregulatory and ventilatory responses to hypoxia in obese Z rats may be attributed to reduced activity of NOS in the central nervous system.
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PMID:Role of nitric oxide in thermoregulation and hypoxic ventilatory response in obese Zucker rats. 1150 Mar 46

Environmental factors such as diet, physical activity, drugs, pollution and life style play an important role in the progression and/or precipitation of diseases like diabetes, hypertension, obesity and cardiovascular disorders. Indiscriminate use of antibiotics to combat infectious diseases is one of the commonest forms of misuse of drugs. Antibiotics seem to have a correlation with diabetes and pancreatic function. There are controversial reports about the effect of antibiotics on the pancreatic islets; some suggesting their harmless action, some depicting a beneficial role and others indicating deleterious effect. Moreover, use of antibiotics is mandatory during islet isolation and cultivation to reduce incidences of microbial contamination. It is likely that antibiotic treatment may adversely affect islet viability and its functioning leading to failure of islet transplantation. The present in vitro study was undertaken to examine the effect of commonly used antibiotics such as gentamycin, penicillin, streptomycin, tetracycline, neomycin, erythromycin and chloramphenicol on islet viability, its functioning and induction of oxidative stress if any. The viability and insulin production data showed that none of the antibiotics used in the present study affect the viability and the functioning of the islets at their pharmacological concentrations. Free radical levels measured in terms of melonyldialdehyde (MDA), nitric oxide (NO) and reduced glutathione (GSH) reveal that except for a marginal increase in lipid peroxidation with tetracycline and slight increase in NO levels with streptomycin, none of these antibiotics affect the oxidative status of the cells. Antioxidant enzymes such as superoxide dismutase and catalase remain unaffected after this treatment. Our results reveal the innocuous nature of the antibiotics used at pharmacological concentrations, suggesting their safety whenever prescribed to combat infections and also during islet isolation procedures.
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PMID:Pancreatic islet-cell viability, functionality and oxidative status remain unaffected at pharmacological concentrations of commonly used antibiotics in vitro. 1156 80

The aims of this study were to elucidate the factors that contribute to endothelial activation and fibrinolytic abnormalities in patients with poorly controlled type 2 diabetes and to determine whether improved glycemic control reduces endothelial activation. Adhesion molecules [E-selectin, intracellular adhesion molecule-1 (ICAM-1), and vascular cell adhesion molecule-1], von Willebrand factor, total nitric oxide (NO), endothelin-1, tissue plasminogen activator, and plasminogen activator inhibitor-1 were measured in 43 type 2 diabetic subjects with hemoglobin A1c of 9.0% or more at baseline (compared with 21 healthy controls) who after 20 wk had been randomized to either improved (IC) or usual (UC) glycemic control. At baseline, type 2 diabetic patients had significant endothelial activation and abnormal fibrinolysis compared with control subjects. Body mass index in the diabetic patients was the only independent predictor of E-selectin (P = 0.007), ICAM-1 (P = 0.01), and NO (P = 0.008) concentrations, but not vascular cell adhesion molecule-1, plasminogen activator inhibitor-1, or tissue plasminogen activator (all P > 0.05). Type 2 diabetic patients with a body mass index of 28 kg/m2 or less had concentrations of E-selectin, ICAM-1, endothelin-1, and NO similar to those in healthy controls. After 20 wk, hemoglobin A1c was significantly lower in IC vs. UC (IC, 8.02 +/- 0.25%; UC, 10.23 +/- 0.23%; P < 0.0001), but there were no significant changes in markers of endothelial activation or indexes of fibrinolysis. Obesity appears to be the most important predictor of endothelial activation in patients with type 2 diabetes. Short-term improvement in glycemic control does not appear to reduce endothelial activation.
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PMID:The influences of obesity and glycemic control on endothelial activation in patients with type 2 diabetes. 1170 27

The purpose of this study was to determine the interdependent and independent effects of hypertension and obesity on endothelial function in humans. We evaluated the forearm blood flow (FBF) response to acetylcholine, an endothelium-dependent vasodilator, and isosorbide dinitrate (ISDN), an endothelium-independent vasodilator, in 16 lean and 12 obese normotensive individuals and the 18 lean and 15 obese hypertensive patients with no history of smoking, hypercholesterolemia, diabetes mellitus, or renal dysfunction. The FBF was measured using a mercury-filled Silastic strain-gauge plethysmograph. The systolic and diastolic blood pressures (BP) and forearm vascular resistance were significantly greater in hypertensive patients than in the normotensive individuals. Insulin resistance, determined by a homeostatic model assessment (HOMA), was significantly greater in the obese group than in the lean group (3.59 +/- 1.68 v 1.91 +/- 1.12, P < .01). There was no significant difference in the HOMA index between normotensive and hypertensive subjects regardless of weight. The response of FBF to acetylcholine was greatest in lean normotensive individuals and least in obese hypertensive patients (40.5 +/- 8.5 and 10.4 +/- 2.8 mL/min/100 mL of tissue, P < .001 v other groups). The FBF response was similar in obese normotensive individuals and lean hypertensive patients (24.1 +/- 7.9 and 19.3 +/- 3.2 mL/min/100 mL of tissue). The vasodilatory effect of ISDN was similar in all four groups. Multiple regression analysis revealed that the maximal FBF response to acetylcholine correlated independently with age (P = .043), obesity (P = .012), HOMA index (P = .002), and mean BP (P < .001). These findings suggest that obesity and hypertension are independently involved in abnormal endothelium-dependent vasodilation by attenuated nitric oxide production.
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PMID:Effect of obesity on endothelium-dependent, nitric oxide-mediated vasodilation in normotensive individuals and patients with essential hypertension. 1171 Jul 83

Obesity may be a low-grade systemic inflammatory disease. Overweight and obese children and adults have elevated serum levels of C-reactive protein, interleukin-6, tumor necrosis factor-alpha, and leptin, which are known markers of inflammation and closely associated with cardiovascular risk factors and cardiovascular and non-cardiovascular causes of death. This may explain the increased risk of diabetes, heart disease, and many other chronic diseases in the obese. The complex interaction between several neurotransmitters such as dopamine, serotonin, neuropeptide Y, leptin, acetylcholine, melanin-concentrating hormone, ghrelin, nitric oxide, and cytokines and insulin and insulin receptors in the brain ultimately determines and regulates food intake. Breast-feeding of more than 12 mo is associated with decreased incidence of obesity. Breast milk is a rich source of long-chain polyunsaturated fatty acids (LCPUFAs) and brain is especially rich in these fatty acids. LCPUFAs inhibit the production of proinflammatory cytokines and enhance the number of insulin receptors in various tissues and the actions of insulin and several neurotransmitters. LCPUFAs may enhance the production of bone morphogenetic proteins, which participate in neurogenesis, so these fatty acids might play an important role in brain development and function. It is proposed that obesity is a result of inadequate breast feeding, which results in marginal deficiency of LCPUFAs during the critical stages of brain development. This results in an imbalance in the structure, function, and feedback loops among various neurotransmitters and their receptors, which ultimately leads to a decrease in the number of dopamine and insulin receptors in the brain. Hence, promoting prolonged breast feeding may decrease the prevalence of obesity. Exercise enhances parasympathetic tone, promotes antiinflammation, and augments brain acetylcholine and dopamine levels, events that suppress appetite. Acetylcholine and insulin inhibit the production of proinflammatory cytokines and provide a negative feedback loop for postprandial inhibition of food intake, in part, by regulating leptin action. Statins, peroxisome proliferator-activated receptor-gamma binding agents, non-steroidal antiinflammatory drugs, and infant formulas supplemented with LCPUFAs, and LCPUFAs themselves, which suppress inflammation, may be beneficial in obesity.
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PMID:Is obesity an inflammatory condition? 1174 55

In the past year there have been many advances in the area of small bowel physiology and pathology and therapy. In preparation for this review, over 1500 papers were assessed. The focus is on presenting clinically useful information for the practising gastroenterologist. Selected important clinical learning points include the following: (1) glucose absorption mediated by SGLT1 is controlled by mRNA abundance, as well as by posttranscriptional processes including protein trafficking; (2) inducers of cytochrome P-450 decrease glucose and fructose absorption and increase glucose consumption in the intestine; (3) the regulated release of nutrients from the stomach into the upper intestine ensures that the modest intestinal transport reserve capacity is not exceeded; (4) hepatocyte growth factor and short-chain fatty acids may enhance intestinal adaptation and prevent the atrophy seen when total parenteral nutrition is infused; (5) inhibitors of pancreatic lipase and phospholipase H2 may be useful clinically to reduce absorption as part of a treatment program for obesity and hyperlipidemia; (6) several membrane-bound and cytosolic proteins have been identified in the enterocyte as well as in the hepatocyte and may be the target for the future therapeutic manipulation of bile acid metabolism and control of hyperlipidemia; (7) suspect bile acid malabsorption in the patient with otherwise unexplained chronic diarrhea; (8) a proportion of lipid absorption is protein-mediated, and this opens the way to targeting these proteins and thereby therapeutically modifying lipid absorption; (9) a high protein diet may be useful to increase the intestinal absorption of drugs transported by the H+/dipeptide cotransporter; (10) a metal transporter DCT1 has been identified, and this may open the way to a better understanding of disorders of, for example, iron and zinc metabolism; (11) the nutrient transporters such as SGLT1 are responsible for a portion of the intestinal absorption of water; (12) the influence of nitric oxide on intestinal water absorption and secretion depends on its concentration; (13) a trial of bile acid-sequestering agent may prove useful in the treatment of the patient who experiences diarrhea while taking an enteral diet; (14) a proteolytic extract from pineapple stems may prove to be useful to treat diarrhea, although the mechanism of this effect remains to be established; and (15) the antisecretory effect of the new peptide, sorbin, needs to be tested in a clinical situation on patients with diarrhea. Other new and promising antidiarrheal agents include bromelain, an extract from pineapple stems, and igmesine, a final sigma ligand.
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PMID:Small bowel review: normal physiology part 1. 1176 47

The endothelium produces a variety of substances that play important roles in regulation of the circulation and vascular wall homeostasis. The control of blood vessel wall homeostasis is achieved via production of vasorelaxants and vasoconstrictors. Among the vasorelaxants are nitric oxide (NO), prostacyclin, various endothelium-derived hyperpolarizing factors (EDHFs, such as cytochrome P-450 monooxygenase metabolites of arachidonic acid like epoxyeicosatrienoic acids, and endocannabinoids), and C-type natriuretic peptide. Among the vasoconstrictors we find endothelin-1 (ET-1) and endothelium-derived contracting factors (EDCF) that are cyclooxygenase products such as endoperoxides and thromboxanes. The endothelium, via these and other agents, also exerts a critical influence on the blood stream, particularly formed elements such as leucocytes and platelets, and on substances involved in blood coagulation. All these effects contribute to modulating the growth of the vascular wall in hypertension, and participate in the development of atherothrombotic complications associated with hypertension. Inhibition of NO production may induce elevation of blood pressure in experimental animals. However, even today, we do not have incontrovertible evidence of participation of NO, EDHFs or EDCFs, or other endothelial products, in the pathogenesis of hypertension, although there is evidence of abnormal endothelium-dependent relaxation in hypertension in many but not all hypertensives. It is unclear, however, to what extent this may precede hypertension or be a consequence of elevated blood pressure, possibly contributing to its complications. Also, it is often difficult to dissociate abnormal endothelium-dependent relaxation from confounding factors such as the presence of associated conditions like dyslipidaemia, diabetes, smoking, obesity, hyperhomocysteinaemia, and others, that are accompanied themselves by abnormal endothelium-dependent relaxation. There is some evidence for a role of ET-1 in blood pressure elevation in some experimental forms of hypertension, particularly severe, sodium-sensitive hypertension, in which it may play a role in accentuating rather than initiating blood pressure elevation. Endothelin-1 may play a similar role in human hypertension.
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PMID:A critical review of the role of endothelial factors in the pathogenesis of hypertension. 1181 73


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