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Anaesthesia for intestinal short circuiting in the morbidly obese with reference to the pathophysiology of gross obesity.

Sixteen extremely obese patients were anaesthetized for intestinal short circuiting operations. Severe obesity may cause pathological cardio-pulmonary changes. Cardiovascular alterations include increased systemic, pulmonary artery and pulmonary capillary venous pressure. Cardiac output, total blood volume and left ventricular work increase. Expiratory reserve volume and consequently functional residual capacity decrease with gross obesity. Functional residual capacity falls below closing volume and inspired gas may be distributed to non-dependent lung zones, resulting in decreased ventilation/perfusion ratios and arterial hypoxaemia. Low total respiratory compliance increases the oxygen cost of the work of breathing. Obesity may change the dose requirements for regional anaesthesia and long-acting muscle relaxants. General anaesthesia may also reduce functional residual capacity. We used a technique of anaesthesia which consisted of epidural analgesia with intra-operative mechanical ventilation and which specifically avoided volatile inhalation agents and long-acting muscle relaxants. All patients were extubated immediately after operation and returned to the recovery room for an average duration of 26 hours. Post-operative treatment included humidified oxygen, chest physiotherapy and elevation of the head of the bed to 45 degrees. Each patient's respiratory progress was monitored by repeated determinations of arterial blood gases and vital capacity and by serial chest X-rays. None of the patients in this group required post-operative tracheal intubation and mechanical ventilation.

Anesthesia, Epidural↗

Variations of thyroid hormones during total fasting in obese and in obese diabetic subjects.

Fasting and hypocaloric diets are known to induce a reduction of triiodothyronine (T3) and to increase reverse triiodothyronine (rT3) in normal and obese subjects. The effect of 8-day fasting was evaluated on T3, thyroxine (T4), free T4, rT3, TSH, immunoreactive insulin (IRI), thyroxine binding globulin (TBG) and glycemia in 21 obese subjects (5 males, 16 females) grouped according to the average starting blood glucose concentration in: group I, diabetic obese subjects (9 patients); group II, non diabetic obese subjects (12 patients). All patients had no history of recent weight loss due to dietetic therapy or drugs. Blood samples were drawn in the morning at 0, 2, 4, 6, 8 days after total caloric deprivation and 2 days after refeeding. A superimposable variation of weight and glucose concentration were seen in both groups. In addition, no difference was observed in ketone body excretion, SH, TBG, T4, free T4. In group II a significant decrease of IRI was observed during diet (p less than 0.05); T3 decreased (p less than 0.01) and rT3 increased (p less than 0.01) significantly. No variations in T3 and rT3 values were observed in group I. These results are consistent with a possible role of glucose metabolism in the genesis of the low T3 syndrome.

Adult↗

Erythrocyte ouabain binding and intracellular Na+ in normotensive obese women and obese women receiving medication for hypertension.

People with "primary obesity" may be hypertensive because they have lost their ability to compensate for the effect of low Na+-K+-ATPase levels on blood pressure. In obese patients receiving hypertensive medication (n = 13), but not in normotensive nonmedicated patients (n = 42), diastolic blood pressure was inversely correlated with erythrocyte ouabain binding (P less than 0.02) and directly correlated with intracellular Na+ concentration (P less than 0.01). Moreover, there was a stronger inverse relationship between ouabain binding and intracellular Na+ in patients receiving medication for hypertension (P less than 0.01) than in normotensive patients (P less than 0.05). These data suggest that patients receiving hypertensive medication may be less able to compensate than normotensive patients, (a) for the potential effect of Na+-K+-ATPase levels on intracellular Na+ and (b) for the potential effect of intracellular Na+ concentration on diastolic blood pressure. We propose that obese people with low levels of ouabain binding (primary obesity) may have an increased risk of developing hypertension if their compensatory mechanisms fail.

Adult↗

Immunocytochemical analysis of somatostatin in the hypothalamus of obese and non-obese Zucker rats.

Levels of growth hormone (GH) are reduced in the genetically obese Zucker rat, fa/fa, in comparison to lean littermates. In normal rats, GH release is regulated by stimulatory and inhibitory factors of hypothalamic origin. The present experiment focuses on hypothalamic somatostatin (SOM; growth hormone release inhibiting factor) in order to determine if abnormal hypothalamic SOM may be a correlate of depressed GH secretion in fa/fa rats. We compared immunocytochemical localization of hypothalamic SOM between 5 obese (fa/fa) Zucker rats and 5 non-obese littermates. Brain sections from pairs of animals were processed simultaneously. The distribution of SOM immunoreactive cell bodies in the hypothalamus agreed with previous reports. SOM-containing neurons in the periventricular area were counted and analyzed at 4 hypothalamic levels: (1) anterior to the suprachiasmatic nucleus (SCN); (2) through SCN; (3) between SCN and the ventromedial hypothalamic nucleus (VMH); and (4) through VMH. The greatest number of SOM-immunoreactive cell bodies was observed at levels (2) and (3). The numbers of SOM-containing cells did not differ significantly between obese and lean animals. No apparent difference in density of fiber staining was observed in the median eminence.

Animals↗

Studies on obesity. III. effect of triiodothyronine (T3) on thyroglobulin autoantibodies in euthyroid obese subjects.

Effect of T3 therapy on tanned red cell agglutinating thyroglobulin (TRC-TG) antibodies in 10 obese subjects without apparent thyroid disease was investigated. Six other obese subjects without thyroid dysfunction and of approximately the same mean age who also had circulating TRC-TG antibodies served as control subjects and were untreated. In vitro thyroid tests (TSH, total and free T4) performed before T3 therapy, as well as clinical examination, showed thyroid function to be normal in all subjects, and there was no evidence of thyroiditis. TRC-TG antibodies were present in low to moderate titers of 40-1280 in control subjects as well as in subjects selected for T3 treatment. Therapy with T3 was started at 50 mug/day and gradually increased to a maximum of 250 mug/day, depending on clinical needs. T3-treated as well as untreated obese control subjects were all maintained on a high protein, low fat, low carbohydrate diet. Duration of T3 therapy varied from 2-8 mo, and in all but one T3-treated subject, TRC-TG antibodies completely disappeared. In the one exceptional case, TRC-TG antibody titer decreased from 1280 to 80 after 7 mo of therapy. In non-T3-treated obese control subjects, antibody titers remained at the same levels throughout the observation period, thereby indicating a lack of spontaneous regression of circulating immune response. Therapy with T3, by inhibiting TSH, may have caused regression of inapparent immunologic thyroid lesion, thus leading to the disappearance of circulating TRC antibodies; alternatively, T3 specifically may have accelerated catabolism of thyroid antibodies. The latter possibility is favored in the absence of clinical and laboratory evidence of thyroiditis in T3-treated subjects.

Adult↗

Atherosclerosis in genetically obese mice: the mutants obese, diabetes, fat, tubby, and lethal yellow.

Mice with five different mutations conferring an obese or diabetic phenotype were evaluated for fatty streak lesions after consuming an atherogenic diet containing 15% fat and 1.25% cholesterol (wt/wt) for 14 weeks. The five mutations, fat, obese, tubby, diabetes, and lethal yellow, are maintained as congenic strains with C57BL/6J (B6) or C57BL/KsJ (BKs) as genetic backgrounds. None of the mutants exhibited accelerated fatty streak lesion formation; the mutant fat had aortic lesions comparable in size to those of its control strain, and the mutants obese, diabetes, tubby, and lethal yellow had significantly reduced lesion area in comparison to controls. Although B6 and BKs are closely related strains, we observed that the BKs strain was more prone to early-stage atherogenesis. Fatty streak lesion area was twice as large in BKs mice than those found in B6 mice; likewise, in comparison, the mutants obese and diabetes had larger lesions if they were carried as congenic strains in the BKs rather than the B6 genetic background. Plasma triglycerides, total cholesterol, high-density lipoprotein cholesterol (HDL-C), and combined low-density and very-low-density lipoprotein cholesterol (LDL-C and VLDL) levels were also measured in the mice. Lipid profiles differed among the mutant mice, but in general, elevations in plasma total cholesterol, triglycerides, and HDL-C were observed. Whereas the hypertriglyceridemia and hypercholesterolemia are consistent with an atherogenic lipid profile, HDL-C levels, which are normally decreased in individuals with non-insulin-dependent diabetes mellitus, were increased in the mouse mutants.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Relationship of obesity to diabetes: influence of obesity level and body fat distribution.

The relationship of clinical diabetes to body fat distribution and obesity level was examined in 15,532 women. After adjusting for relative weight, all upper body segment girth measurements (neck, bust, and waist) had strong positive associations with diabetes. In contrast, the lower body segment girth measurement (hips) had an equally strong but inverse association with diabetes. Based upon waist-to-hip girth ratio, women were divided into four subgroups. The prevalence of diabetes increased with increasing values of this ratio. Women in the upper quartile had about three times the prevalence of diabetes as women of comparable obesity level in the lowest quartile. Women with both upper body fat predominance and severe obesity had a relative risk of diabetes 10.3 times as great as nonobese subjects with lower body fat predominance. The results suggest that localization of fat in the upper body segment and severe obesity are two distinct additive risks for diabetes.

Adipose Tissue↗

Long-term effects of diethylstilbestrol (DES) on genetically obese and non-obese female Zucker rats.

The long-term effects of diethylstilbestrol (DES) were studied in genetically obese and non-obese female Zucker rats. Experimental animals were implanted subcutaneously with a 15 mg pellet of DES at the beginning of the experiment, and again three months later. Weight-matched control animals received no treatment. Rats were sacrificed 6.5 months after the first implantation. The animals treated with DES had significantly lower body weights at sacrifice than the control rats; the percentage reduction was comparable for the obese and lean animals. Treatment was associated with significant reductions in body length, food intake, water intake and weights of an inguinal fat pad, heart, liver, kidneys and adrenals. In contrast, weight of the reproductive tract and pituitary gland were significantly higher in the treated rats. Effects of DES treatment were comparable in lean and obese rats.

Animals↗

The effects of low-dose Bay-m-1099 (Miglitol) on serum lipids and liver enzyme activity of obese and obese-diabetic corpulent rats.

1. Groups of lean, obese, and obese-non-insulin-dependent diabetic LA/N-cp and SHR/N-cp rats were administered the a-glucosidase inhibitor Miglitol (150 mg/kg diet, ad libitum) from 8 until 15 weeks of age. 2. Phenotype effects (obese greater than lean) were present for weight gain, adiposity, serum glycemic and lipid parameters, and for liver glucokinase, glucose-6-phosphate dehydrogenase, and malic enzyme activity. Miglitol treatment was associated with improvements in glucokinase and malic enzyme in both strains, and in improvements in glycemic parameters in obese rats. 3. These results are consistent with variable improvements in glycemic control and insulin action following low dose Miglitol treatment, and indicate that indirect effects of the drug on insulin sensitivity in peripheral tissues and on glucoregulatory enzymes may contribute to the glycemic improvements observed with this drug, while greater dosages or longer treatment may be required to observe comparable improvements in adiposity or plasma lipid profiles.

1-Deoxynojirimycin↗

Low-carbohydrate diets cause obesity, low-carbohydrate diets reverse obesity: a metabolic mechanism resolving the paradox.

High-fat diets produce obesity in part because, per calorie, glucose produces greater post-prandial thermogenesis than lipids, an effect probably mediated by glucose-sensing neurons. A very low-carbohydrate/high-fat/high-protein Atkins-type diet produces obesity but is marginally ketogenic in mice. In contrast, high-sucrose/low-fat diets, and very low-carbohydrate/high-fat/low-protein (anti-epileptic) ketogenic diets reverse diet-induced obesity independent of caloric intake. We propose that a non-ketogenic high-fat diet reduces glucose metabolism and signaling in glucose-sensing neurons, thereby reducing post-prandial thermogenesis, and that a ketogenic high-fat diet does not reduce glucose signaling, thereby preventing and/or reversing obesity.

Blood Glucose↗

Chronic withdrawal of a high-palatable obesity-inducing diet completely reverses metabolic and vascular abnormalities associated with dietary-obesity in the rat.

Chronic consumption of a high-palatable diet induces obesity and markedly impairs arterial relaxation. We have recently reported that endothelial function is only partially resorted after acute withdrawal of palatable diet. Therefore, this study was designed to investigate the effects of chronic withdrawal of high-palatable obesity-inducing diet on metabolic and vascular function in rats. Wistar rats were fed either standard laboratory chow throughout (controls) or given a highly-palatable diet (diet-fed) for 15 weeks; or fed the diet for 8 weeks and then returned to chow (diet-to-chow) for further 7 weeks before sacrifice. Diet-fed rats had higher body weight, fat mass, liver and heart weight than both chow-fed and diet-to-chow groups (P<0.01 for all). Compared with chow-fed and diet-to-chow groups, diet-fed rats had significantly raised fasting plasma levels of insulin, leptin and triglycerides levels (each +180%; P<0.0001), but not glucose or non-esterified fatty acids. There were no significant differences between any metabolic parameters between chow-fed and diet-to-chow groups. Mesenteric arteries showed no significant differences between any groups in KCl-induced tension generation, while diet-fed groups had significantly higher noradrenaline-induced vasoconstriction than both chow-fed and diet-to-chow groups. Maximum endothelial-dependent vasorelaxation responses to carbamylcholine (CCh) were significantly (by 23%; P<0.001) attenuated in the diet-fed group. This defect was abolished in the diet-to-chow group. There were no significant differences in endothelium-independent vasorelaxation responses to sodium nitroprusside between the three groups. In conclusion, palatable diet induces obesity and metabolic abnormalities as well as a marked endothelial dysfunction. These abnormalities are completely reversed by chronic withdrawal of the obesity-inducing high-palatable diet.

Animals↗

Chronic stress reduces body fat content in both obesity-prone and obesity-resistant strains of mice.

Unpredictable stressors have been used to assess the effect of stress on energy metabolism in obesity-prone (C57BL6J) and obesity-resistant (AJ) mice. Mice were exposed for 25 days to a stress protocol. Both strains of mice were divided into groups of control and stressed mice, which had access to either a high-fat or a high-carbohydrate diet. Twenty-four hours after the last session of stress, mice were sacrificed for blood and brain collections. Insulin, corticosterone, and glucose concentrations in plasma were measured, and expressions of corticotropin-releasing factor (CRF) in the paraventricular hypothalamic nucleus (PVH) and the central amygdala (CeA) were determined by in situ hybridization. Stressed mice in all groups had lower body fat contents than control mice, and all mice fed with the high-fat diet had heavier retroperitoneal and inguinal fat pads than mice fed with carbohydrate. CRF mRNA level in the CeA was lower in B6 mice than in AJ mice. Stressed mice had a lower expression of CRF in the CeA than control mice. In conclusion, chronic stress reduces body fat content in obesity-prone as well as in obesity-resistant mice.

Adipose Tissue↗

Assessment of emotional, externally induced and restrained eating behaviour in nine to twelve-year-old obese and non-obese children.

Are there differences in eating behaviour between obese and non-obese children? Using the parent version of the Dutch Eating Behaviour Questionnaire (DEBQ-parent version), the results of the present study suggest an affirmative answer to this question. The scores for obese children were significantly higher on the scales for emotional, external and restrained eating behaviour. Relationships were found between emotional eating and negative feelings of physical competence; between external eating and negative feelings of self-worth; and between both eating styles and various aspects of problem behaviour. No relationship was found between external eating and locus of control. Higher scores on both scales were associated with greater caloric intake. These findings suggest that DEBQ can be used as a screening instrument for assessing eating styles of obese children.

Analysis of Variance↗

Central leptin gene delivery evokes persistent leptin signal transduction in young and aged-obese rats but physiological responses become attenuated over time in aged-obese rats.

The purpose of this study was to determine if long-term leptin treatment desensitizes leptin signal transduction and the subsequent downstream anorexic and thermogenic responses in normal and leptin-resistant age-related obese rats. To this end, we administered, i.c.v., recombinant adeno-associated virus encoding rat leptin cDNA (rAAV-leptin) or control virus into young and aged-obese rats and after 9 or 46 days, examined food intake, oxygen consumption, body weight, serum leptin, STAT3 phosphorylation, hypothalamic NPY and POMC mRNAs, and UCP1 expression and protein level in brown adipose tissue (BAT). In young rats, rAAV-leptin depleted body fat and both anorexic and thermogenic mechanisms contributed to this effect. Moreover, leptin signal transduction was not desensitized, and there were persistent physiological responses. Similarly, in the aged-obese rats, there was unabated leptin signal transduction, however, both the anorexic and thermogenic responses completely attenuated sometime after day 9. This attenuation, downstream of the leptin receptor, may be contributing to the leptin-resistance and age-related weight gain in these aged-obese rats. Finally, in young rats, although the initial responses to rAAV-leptin were dominated by anorexic responses, by 46 days, the predominant response was thermogenic rather than anorexic, suggesting that energy expenditure may be an important component of long-term weight maintenance.

Adipose Tissue, Brown↗

Differential satiating effects of fats in the small intestine of obesity-resistant and obesity-prone rats.

The effects of duodenal infusions of fats on sham feeding was measured in two strains of rats that differ in their susceptibility to fat-induced obesity. Osborne-Mendel rats are prone to developing obesity on a high-fat diet and preferentially choose fats over carbohydrates in macronutrient selection paradigms. In contrast, S 5B/PL rats are resistant to developing obesity when eating a high-fat diet, and preferentially choose carbohydrates in macronutrient selection paradigms. To test the hypothesis that differences in the satiating potency of fats in the small intestine contributed to these differences between the two strains, we measured the effects of duodenal infusions of Intralipid and sodium linoleate on sham-feeding intakes. The results were consistent with the hypothesis. Duodenal infusions of either of these fats decreased intake significantly more in S5B/PL rats than in Osborne-Mendel rats. Both rat strains sham fed similar amounts when intestinally infused with 0.15 M NaCl. These results suggest that differences in responses to intestinal satiating mechanisms may contribute to the differences in susceptibility to fat-induced obesity in these rat strains.

Animals↗

A new approach to multicultural item generation in the development of two obesity-specific measures: the Obesity and Weight Loss Quality of Life (OWLQOL) questionnaire and the Weight-Related Symptom Measure (WRSM).

BACKGROUND: Being overweight or obese has substantial effects on individuals' perceptions of their health and quality of life (QoL). Generic measures often miss important QoL information, and existing obesity-specific instruments have shortcomings with respect to cross-cultural input, application to differing levels of severity, conceptual clarity, and patient burden. OBJECTIVE: This study aimed to develop culturally sensitive measures of QoL and symptoms in overweight or obese persons, both those trying to lose weight and those not trying to lose weight. METHODS: Currently accepted criteria and guidelines for questionnaire development were streamlined and augmented to include cross-cultural input from 5 European countries and the United States. The preliminary pool of items was created based on qualitative interviews conducted in the United States, followed by an early check of item translatability and preharmonization across all languages. Ten additional qualitative in-country interviews were then conducted to produce further culture-specific items. This was followed by 2 forward and 1 backward translation, plus cognitive debriefing interviews in each country. Finally, an expanded international harmonization meeting was held to ensure inclusion of appropriate new items and their acceptability across all 6 cultures. RESULTS: The procedures described resulted in development of the 41-item Obesity and Weight Loss Quality of Life questionnaire and the 20-item Weight-Related Symptom Measure. These questionnaires are subject to further psychometric validation. CONCLUSIONS: Augmentation of the initial item-generation and international harmonization steps of questionnaire development through integration of cross-cultural input allowed greater validity of cross-cultural content while meeting time, budget, and resource constraints.

Adult↗

The impact of obesity on the short-term and long-term outcomes after percutaneous coronary intervention: the obesity paradox?

OBJECTIVES: The purpose of this study was to assess the impact of body mass index (BMI) on the short- and long-term outcomes after percutaneous coronary intervention (PCI). BACKGROUND: Obesity is associated with advanced coronary artery disease (CAD). However, the relation between BMI and outcome after PCI remains controversial. METHODS: We studied 9,633 consecutive patients who underwent PCI between January 1994 and December 1999. Patients were divided into three groups according to BMI: normal, BMI between 18.5 and 24.9 (n = 1,923); overweight, BMI between 25 and 30 (n = 4,813); and obese, BMI >30 (n = 2,897). RESULTS: Obese patients were significantly younger and had consistently worse baseline clinical characteristics than normal or overweight patients, with a higher incidence of hypertension, diabetes, hypercholesterolemia and smoking history (p < 0.0001). Despite similar angiographic success rates among the three groups, normal BMI patients had a higher incidence of major in-hospital complications, including cardiac death (p = 0.001). At one-year follow-up, overall mortality rates were significantly higher for normal BMI patients compared with overweight or obese patients (p < 0.0001). Myocardial infarction and revascularization rates did not differ among the three groups. By multivariate Cox regression analysis, diabetes, hypertension, age, BMI and left ventricular function were independent predictors of long-term mortality. CONCLUSIONS: In patients with known CAD who undergo PCI, very lean patients (BMI <18.5) and those with BMI within the normal range are at the highest risk for in-hospital complications and cardiac death and for increased one-year mortality.

Age Factors↗

Surgery as an intervention for obesity. Results from the Swedish obese subjects study.

The prevalence of obesity is increasing dramatically all over the world, leading to suffering as well as high health care costs due to obesity-related co-morbidity. Long-term results from weight loss studies are hard to attain due to the difficulties in sustaining weight losses. Gastric surgery results in large and maintainable weight reductions. The Swedish obese subjects (SOS) study offers a unique possibility for investigating the effects of weight loss as compared with weight stability in obese subjects over a long period of time.

Adult↗