Truncal adiposity impairs ventilation in obese adults by altering normal ventilatory mechanics. Leptin, an inflammatory adipocytokine, is elevated in obesity and has been shown to alter ventilatory responses to exercise. Leptin’s bioavailability appears to be regulated by its soluble receptor (LRe), which is reduced in obesity. Roux-en-Y gastric bypass surgery (RYGBS) is a weight loss intervention that reduces total fat mass and improves several obesity related co-morbidities including pulmonary dysfunction. The purpose of this study was to first evaluate the differences between ventilatory responses to carbon dioxide (VE/VCO2 slope) during progressive treadmill walking in morbidly obese and normal weight females. Second, we will analyze the relationships between the VE/VCO2 slope, truncal adiposity, serum leptin, and LRe. Lastly, we want to evaluate the changes in the ventilatory responses to exercise (VE/VCO2 slope), truncal adiposity, serum leptin, and LRe 3 months following Roux-en Y gastric bypass surgery. Thirteen obese (OB 37.7 ±11.4 years, 42.0 ± 4.8 kg/m2) and 12 normal weight females (NW 36.1 ±8.0 years, 22.8 ± 1.2 kg/m2) participated in this study. Blood samples for measure of fasting serum leptin and soluble leptin receptor were obtained prior to exercise. Cardiopulmonary variables were measured throughout exercise. Regional adiposity was determined through dual energy x-ray absorptiometry. Truncal adiposity was significantly greater in the obese group than the normal weight group. Serum leptin was greater in the obese group while LRe was lower than the normal weight group. The VE/VCO2 slopes were lower in obese group when compared to the normal weight group. There were no significant group differences in maximal ventilation, tidal volume or respiratory rate. Stepwise regression determined that truncal adiposity accounted for 31.5% of variance in VE/VCO2 slope (R= 0.561, R2 =0.315, p = 0.004). At 3 months post-surgery we observed significant reductions in the obese group in total percentages of fat, truncal adiposity, serum leptin. The soluble leptin receptor was not changed at any measured time point following RYGBS. There were no changes in 3 months post-surgery VE/VCO2 slopes in the obese group. Truncal adiposity, serum leptin and LRe were associated with reduced ventilatory responses to weight bearing exercise (VE/VCO2 slope) in obese females when compared to normal weight females. There were no differences between obese and normal weight females in maximal minute ventilation, tidal volume or respiratory rate. This result suggests that differences in VE/VCO2 slopes may not be entirely from maximal pulmonary capacity. Rather, the differences in VE/VCO2 slope may be attributed to truncal adiposity and its positive relationship with leptin. Elevated leptin in the obese group may indicate a state of central leptin resistance which has been shown to reduce the ventilatory responses to exercise. At 3 months post RYGBS significant reductions in total percent fat, serum leptin, truncal adiposity and BMI were observed. However, despite improvement in fat mass and serum leptin there were no changes in the VE/VCO2 slope and LRe at 3 months post RYGBS. Therefore, it is possible that the improvements in body composition and leptin following RYGBS were not sufficient to increase ventilation responses to weight bearing exercise in obese females.

The aims of the study were to obtain a method with which it would be possible to produce standardized wounds in the gastric mucosa, and to follow the regeneration of the acid producing parietal cells in those lesions during different experimental conditions. Quantitative methods applied to light and electron microscopy were used. Wounds were cauterized in the corpus mucosa in Sprague-Dawley rats and in addition, pyloroplasty, truncal vagotomy with pyloroplasty or ant- rectoiriy were performed. Other groups of rats with wounds were given long-term treatment with pentagastrin or cimetidine. Stimulation tests were carried out in two groups of wound operated rats. After different periods of time the animals were perfusion fixed and specimens from the wounds and normal mucosa beside the wounds were pre­pared for light and electron microscopy. By means of stereological techniques, different mucosal and cellular structures were then measur­ed. Parietal cells were found in 90 days old wounds. At this stage they were immature with large nuclei and few specialized cell organelles. In spite of this appearance they were able to respond morphologically to stimulation and to secrete acid. With further healing the morphology of the parietal cells became normal, but their volume fraction in the mucosa remained subnormal. The fraction of mucosa occupied by epithel­ial cells also stayed lower than normal. Pyloroplasty resulted in decreased cell and nuclear size of both normal and regenerating parietal cells. In the latter, there was also a de­crease in the mitochondrial volume density. If a truncal vagotomy was added to the pyloroplasty these changes disappeared and, in addition, an increase in parietal cell volume density was noticed in the normal mucosa. Antrectorny produced smaller parietal cells, and their maturation was delayed. Furthermore, mucosal thickness decreased. If pentagastrin was given to rats with wounds an increase in the number of parietal cells was noted, but maturation and morphology remained unaffected. Cimetidine treatment did not affect the parietal cell volume density in wounds or normal mucosa. However, a large increase in the secretory surface density was noticed when the effect of the last dose had ceas­ed. / <p>S. 1-45: sammanfattning, s. 47-121 utgörs av 5 uppsatser</p> / digitalisering@umu