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

We sought to determine whether the fa (leptin receptor) mutation was a major determinant of the putative obesity effects on respiratory frequency in an intercross between the Brown Norway (low breathing frequency, nonobese strain) and the Zucker (moderately high breathing frequency, with the fa mutation) strains. The hypothesis was that rats bearing one (heterozygote) or two (homozygote) alleles of the Glu296Pro point mutation (fa) would have a uniformly high respiratory frequency in the second filial (F2) generation, compared with wild-type animals. In addition to breathing frequency, tidal volume and minute ventilation were assessed during baseline, acute hypoxic (10% O2-0% CO2-balance nitrogen), hypercapnic (93% O2-7% CO2), hyperoxic (100% O2-0% CO2), and combined (10% O2-3% CO2-balance nitrogen) challenges in fa homozygote (fa/fa; n = 24), fa heterozygote (fa/wt; n = 33), and wild-type (wt/wt; n = 19) animals. Phenotypes were adjusted with stepwise regression analyses for the effects of age, sex, length, and litter size. Broad-sense heritability was estimated by examining the variance of the traits in first filial and F2 generations. ANOVAs were used to determine the mode of inheritance of the fa allele in the F2 generation. As anticipated, weight demonstrated the greatest overall broad-sense heritability (77%) and was the result of the recessive mutation. Breathing parameters during the hypoxic, hypercapnic, and combined challenges demonstrated a wide range of heritability from 5 to 96%, with a very nonuniform proportion of heritability explained by the leptin receptor. At best, for frequency 4.5 min into the hypercapnic hypoxic challenge, approximately 20% of the total heritability (approximately 67%) could be attributed to an effect of the leptin receptor mutation. We conclude that, unlike its major effect on weight, the effect of the fa allele is not a major gene involved in the regulation of breathing frequency.
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PMID:The fa leptin receptor mutation and the heritability of respiratory frequency in a Brown Norway and Zucker intercross. 1503 67

We report a case of a 35-year-old woman with myotonic dystrophy and severe obesity of BMI 43.3 who showed persistent apnea at emergence after ovarian resection. The patient received an iv induction with minimum dose of propofol and vecuronium 3 mg. Anesthesia was maintained with propofol, 50% nitrous oxide and 50% oxygen mixture and epidural anesthesia. Additional vecuronium 0.5 mg was administered twice. Surgery was performed uneventfully within 130 minutes and iv propofol was discontinued. The patient awoke promptly after termination of nitrous oxide but no spontaneous breathing appeared with end-tidal CO2 of 60 mmHg. Because she could obey the order to breathe, the endotracheal tube was removed 40 minutes after discontinuation of propofol. Spontaneous breathing at the rate of 17 x min(-1) started soon after extubation. We assume that this apnea was caused by breath holding. Whether this breath holding is specific to myotonic dystrophy or not, anesthesia for patients with this disease requires careful attention for perioperative respiratory management.
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PMID:[Persistent apnea in an obese patient with myotonic dystrophy]. 1596 86

The role of ingested fat in the etiology of obesity is controversial. The aims of this study were to determine the contributions of ingested fat oxidation to: 1) 24-h total energy expenditure (TEE), and 2) substrate oxidation during acute stationary cycle exercises in adult humans. Healthy, moderately obese (n = 18; BMI = 31 +/- 1 kg/m2) subjects (8 men; 10 women) were each studied in a whole-room calorimeter for 24 h. They were fed mixed meals (55, 30, and 15% as energy from carbohydrate, fat and protein, respectively) to maintain energy balance. Each subject performed 1255-kJ cycle exercises at 50% VO2max in the calorimeter. Study test meal fat was labeled with carbon-13 (13C). Ingested fat oxidation was estimated from breath 13CO2 excretion and the subject's chamber CO2 production. Total fat and carbohydrate oxidations were estimated from nonprotein respiratory quotient (NP-RQ) values. Endogenous fat oxidation was estimated as the difference between total fat and ingested fat oxidations. TEE was estimated from gas exchanges; 28 +/- 3% of ingested fat was oxidized and it provided 8 +/- 1% of 24-h TEE. During cycle exercises, ingested fat provided 50% of total fat oxidized and 13.0 +/- 2% of energy expended. Endogenous fat oxidation contributed 10.4 +/- 3% of energy expenditure during cycle exercises. This study extended to 24-h observations of previous studies that lasted 6-9 h on ingested fat oxidation in humans. Understanding the factors that promote ingested fat oxidation could lead to more effective obesity intervention programs.
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PMID:Ingested fat oxidation contributes 8% of 24-h total energy expenditure in moderately obese subjects. 1614 Aug 92

The PCK1 gene (Pck1 in rodents) encodes the cytosolic isozyme of phosphoenolpyruvate carboxykinase (PEPCK-C), which is well-known for its function as a gluconeogenic enzyme in the liver and kidney. Mouse studies involving whole body and tissue-specific Pck1 knockouts as well as tissue-specific over-expression of PEPCK-C have resulted in type 2 diabetes as well as several surprising phenotypes including obesity, lipodystrophy, fatty liver, and death. These phenotypes arise from perturbations not only in gluconeogenesis but in two additional metabolic functions of PEPCK-C: (1) cataplerosis which maintains metabolic flux through the Krebs cycle by removing excess oxaloacetate, and (2) glyceroneogenesis which produces glycerol-3-phosphate as a precursor for fatty acid esterification into triglycerides. PEPCK-C catalyzes the conversion of oxaloacetate + GTP to phosphoenolpyruvate + GDP + CO2. It is in part the tissue-specificity of this simple reaction that results in the variety of phenotypes listed above. Briefly: (1) A 7-fold over-expression of PEPCK-C in the livers of mice causes excessive glucose production. (2) Mice with a whole-body knockout of Pck1 die within 2-3 days of birth, not from hypoglycemia, but probably because the Krebs cycle slows to approximately 10% of normal in the absence of cataplerosis. (3) Mice with a liver-specific knockout have an inability to remove oxaloacetate from the Krebs cycle, which leads to a fatty liver following a fast. (4) An adipose-specific knockout of Pck1 results in a fraction of the mice developing lipodystrophy due to lost glyceroneogenesis and a consequent decrease in fatty acid re-esterification. (5) Finally, disregulated over-expression of PEPCK-C in adipose tissue increases fatty acid re-esterification leading to obesity. These varied experimental phenotypes in mice have led us to postulate that abnormal production of PEPCK isozymes encoded by two PEPCK genes, PCK1 and PCK2, in humans could have similar consequences (Beale, E. G. et al. (2004). Trends in Endocrinology and Metabolism, 15, 129-135). The purpose of this review is to further explore these possibilities.
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PMID:PCK1 and PCK2 as candidate diabetes and obesity genes. 1770 78

The X-linked orphan receptor GPR50 shares 45% homology with the melatonin receptors, yet its ligand and physiological function remain unknown. Here we report that mice lacking functional GPR50 through insertion of a lacZ gene into the coding sequence of GPR50 exhibit an altered metabolic phenotype. GPR50 knockout mice maintained on normal chow exhibit lower body weight than age-matched wild-type littermates by 10 wk of age. Furthermore, knockout mice were partially resistant to diet-induced obesity. When placed on a high-energy diet (HED) for 5 wk, knockout mice consumed significantly more food per unit body weight yet exhibited an attenuated weight gain and reduced body fat content compared with wild-type mice. Wheel-running activity records revealed that, although GPR50 knockout mice showed no alteration of circadian period, the overall levels of activity were significantly increased over wild types in both nocturnal and diurnal phases. In line with this, basal metabolic rate (O2 consumption, CO2 production, and respiratory quotient) was found to be elevated in knockout mice. Using in situ hybridization (wild-type mice) and beta-galactosidase activity (from LacZ insertion element in knockout mice), brain expression of GPR50 was found to be restricted to the ependymal layer of the third ventricle and dorsomedial nucleus of the hypothalamus. GPR50 expression was highly responsive to energy status, showing a significantly reduced expression following both fasting and 5 wk of HED. These data implicate GPR50 as an important regulator of energy metabolism.
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PMID:Altered metabolism in the melatonin-related receptor (GPR50) knockout mouse. 1795 37

In the Western world, the prevalence of the metabolic syndrome is increasing exponentially. Chronic subacute inflammation characterizes the syndrome, suggesting that inflammation might be a common denominator that links obesity to its pathologic sequelae. Potential mechanisms for the activation of inflammation include current air pollution inhalation and/or excess food intake. Both of these environmental factors have, in fact, been shown to promote oxidation followed by the release of proinflammatory cytokines. Potential sources of systemic inflammation include oxidized erythrocytes. Increased exogenous or endogenous CO2 deoxygenates hemoglobin, thereby increasing the fraction of hemoglobin reacting with nitrite to form methemoglobin together with release of superoxide and nitric oxide. These may form peroxynitrite, which may oxidize erythrocytes. Macrophages may then recognize and engulf these cells, thereby releasing proinflammatory cytokines. Therefore, studies should focus on the red blood cell and its proteins to finely target and appropriately treat a world pandemic ominously related to CO2 increases.
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PMID:Environmental stress, erythrocyte dysfunctions, inflammation, and the metabolic syndrome: adaptations to CO2 increases? 1832 83

The present study is the first to compare the cardiorespiratory responses during progressive weight-bearing treadmill exercise in normal-weight non-pregnant (NP, n=14), normal-weight pregnant (PG, n=20) and obese pregnant (PGOB, n=20) women. Exercise duration and peak treadmill speed were lower in PG (23.9+/-4.9 min; 1.6+/-0.2m/s; P<0.001) compared to NP (33.7+/-4.9 min; 2.0+/-0.2m/s) and were further reduced in PGOB (19.6+/-2.8 min; 1.4+/-0.1m/s; P<0.001) indicating a performance limitation to exercise. Ventilation in response to exercise was increased in PG (49.4+/-6.6L/min) compared to NP (39.8+/-5.4 L/min, at 100W; p<0.05) women, and was further augmented by obesity (56.7+/-9.3 L/min, at 100W; p<0.05 versus PG) secondary to an elevated metabolic cost of exercise as indicated by no further increase in .V(E)/.V(CO2) and .V(E)/.V(O2) in PGOB compared to PG women. The normal augmentation of heart rate observed in PG during exercise was not further increased by obesity at standardized sub-maximal work rates.
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PMID:Impact of pregnancy and obesity on cardiorespiratory responses during weight-bearing exercise. 1953 87

Adverse surgical outcomes appear to be more frequent in patients with known obstructive sleep apnea (OSA). However, OSA patients may present for surgery without a prior diagnosis. A 37-year-old man underwent craniotomy for surgical direct neck clipping of the right ruptured internal carotid aneurysm. His intraoperative and early postoperative courses were uneventful. At night, about 48 hr after surgery, he developed sudden generalized tonic-clonic convulsion and temporary depressed consciousness resulting in marked hypercapnea (Pa(CO2)>100 mmHg). His respiration was transiently supported by PSV mode via LMA. He soon got well without neurologic deficits. At night, about 74 hr postoperatively, a generalized convulsion was again observed with hypercapnea. Aside from the respiratory support, percutaneous cricothyroidotomy was performed using Minitrach II system for his airway control, leading to no further recurrence of seizure. He was suspected to have unrecognized OSA due to such characteristic findings of sleep apnea as obesity (BMI>30) and witnessed apneas by his family. Postoperative rapid eye movement (REM) sleep rebound has been suggested to contribute to two consecutive night appearance of seizure. Clinical suspicion for OSA should be required preoperatively and perioperative heightened awareness is recommended.
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PMID:[Case of obstructive sleep apnea possibly having led to postoperative appearance of generalized convulsion]. 2042 Jan 47

Altitude travel results in acute variations of barometric pressure, which induce different degrees of hypoxia, changing the gas contents in body tissues and cavities. Non ventilated air containing cavities may induce barotraumas of the lung (pneumothorax), sinuses and middle ear, with pain, vertigo and hearing loss. Commercial air planes keep their cabin pressure at an equivalent altitude of about 2,500 m. This leads to an increased respiratory drive which may also result in symptoms of emotional hyperventilation. In patients with preexisting respiratory pathology due to lung, cardiovascular, pleural, thoracic neuromuscular or obesity-related diseases (i.e. obstructive sleep apnea) an additional hypoxic stress may induce respiratory pump and/or heart failure. Clinical pre-altitude assessment must be disease-specific and it includes spirometry, pulsoximetry, ECG, pulmonary and systemic hypertension assessment. In patients with abnormal values we need, in addition, measurements of hemoglobin, pH, base excess, PaO2, and PaCO2 to evaluate whether O2- and CO2-transport is sufficient.Instead of the hypoxia altitude simulation test (HAST), which is not without danger for patients with respiratory insufficiency, we prefer primarily a hyperoxic challenge. The supplementation of normobaric O2 gives us information on the acute reversibility of the arterial hypoxemia and the reduction of ventilation and pulmonary hypertension, as well as about the efficiency of the additional O2-flow needed during altitude exposure. For difficult judgements the performance of the test in a hypobaric chamber with and without supplemental O2-breathing remains the gold standard. The increasing numbers of drugs to treat acute pulmonary hypertension due to altitude exposure (acetazolamide, dexamethasone, nifedipine, sildenafil) or to other etiologies (anticoagulants, prostanoids, phosphodiesterase-5-inhibitors, endothelin receptor antagonists) including mechanical aids to reduce periodical or insufficient ventilation during altitude exposure (added dead space, continuous or bilevel positive airway pressure, non-invasive ventilation) call for further randomized controlled trials of combined applications.
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PMID:Fit for high altitude: are hypoxic challenge tests useful? 2295 73

Human obesity has evolved into a global epidemic. Interestingly, a similar trend has been observed in many animal species, although diet composition, food availability and physical activity have essentially remained unchanged. This suggests a common factor-potentially an environmental factor affecting all species. Coinciding with the increase in obesity, atmospheric CO2 concentration has increased more than 40%. Furthermore, in modern societies, we spend more time indoors, where CO2 often reaches even higher concentrations. Increased CO2 concentration in inhaled air decreases the pH of blood, which in turn spills over to cerebrospinal fluids. Nerve cells in the hypothalamus that regulate appetite and wakefulness have been shown to be extremely sensitive to pH, doubling their activity if pH decreases by 0.1 units. We hypothesize that an increased acidic load from atmospheric CO2 may potentially lead to increased appetite and energy intake, and decreased energy expenditure, and thereby contribute to the current obesity epidemic.
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PMID:A proposed potential role for increasing atmospheric CO2 as a promoter of weight gain and obesity. 2344 30


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