京都大学 / 0048 / 新制・課程博士 / 博士(医学) / 甲第22365号 / 医博第4606号 / 新制||医||1043(附属図書館) / 京都大学大学院医学研究科医学専攻 / (主査)教授 岩田 想, 教授 川上 浩司, 教授 横出 正之 / 学位規則第4条第1項該当 / Doctor of Medical Science / Kyoto University / DFAM

One of the major healthcare issues found almost worldwide, especially in the United States, is the obesity epidemic. Obesity is known to have deleterious effects on many body/organ systems. C1q TNF-related protein-3 (CTRP3) is effective at preventing high-fat diet-induced fatty liver. With these two factors taken into consideration, this study explores the possible effects of a high caloric diet on the muscle wall of the uterus, i.e., the myometrium, and how over-expression of CTRP3 may modify those effects. We hypothesize that consumption of excessive amounts of fat and sugar will have detrimental effects on the dual layers of the mouse myometrium. For this study, 17 mice were divided into 4 treatment groups: wild type/low fat diet, wild type/high fat diet, CTRP3-overexpressing/low fat diet, and CTRP3-overexpressing/high fat diet. The mice were placed on their respective diets at 7 weeks of age with a feeding duration of 12 weeks. At the conclusion of the feeding protocol, the female reproductive tissues were harvested and fixed in 4% paraformaldehyde and subsequently paraffin embedded. The uterine horns of each mouse were painstakingly paraffin embedded in a vertical position so that cross sections of the uterus could be obtained and measured. These 4µ sections were stained using standard H&E staining techniques and visualized under light microscopy. A randomization grid was utilized to determine measurement locations on the tissue. For each animal, 15 measurements were made of the outer longitudinal layer of the uterine horn, as well as 15 measurements of the inner circular layer, and 15 measurements of the thickness of the two layers combined. Two-way ANOVA was used to determine if any changes seen were statistically significant. At the time of the writing of this abstract, no appreciable differences have been found between the treatment groups, although there will be more data and final statistics completed before the presentation of our findings.

C1q TNF-related protein-3 (CTRP3) is effective at preventing high-fat diet-induced fatty liver; Recent studies have shown that overexpression of C1q TNF-related protein-3 (CTRP3) in mice fed a high alcohol diet can protect the animal from developing fatty liver disease, and therefore may be a possible treatment for alcoholic fatty liver disease (ALD). However, the possible effects of overexpression of CTRP3 on other tissue has not been widely investigated. If overexpression of CTRP3 proves to be harmful to other tissues, its use as a treatment for ALD would come into question. This study utilized kidney tissue from mice that were fed a high fat diet for 13-14 weeks. The feeding started when the mice were 7 weeks old and continued for 9 weeks. The mice were divided into 4 categories: wild-type/low fat diet, wild-type/high fat diet, transgenic/low fat diet, and transgenic/high fat diet. The kidneys were harvested and fixed in 4% paraformaldehyde and subsequently paraffin embedded. Sections were cut at 4µ and stained using three different staining techniques: standard H&E, Periodic Acid Schiff (PAS), and Masson’s Trichrome Staining. These three methods were utilized to better visualize possible effects on the tissue, i.e. changes in connective tissue deposition or basement membrane thicknesses, etc. Light microscopic examination of the tissues to date has revealed abnormalities in some of the kidney tubules in the transgenic high fat diet group. These same abnormalities have not been observed in the other treatment groups. This study is still in its early stages and much more in-depth investigation is needed to determine which of the tubules of the nephron are affected, and what this effect is. If this study confirms that overexpression of CTRP3 coupled with a high fat diet is harmful to kidney tissues, the use of CTRP3 in the treatment of ALD would require careful monitoring of the patient’s diet.

京都大学 / 0048 / 新制・課程博士 / 博士(人間健康科学) / 甲第18194号 / 人健博第11号 / 新制||人健||1(附属図書館) / 31052 / 京都大学大学院医学研究科人間健康科学系専攻 / (主査)教授 細田 公則, 教授 高桑 徹也, 教授 任 和子 / 学位規則第4条第1項該当 / Doctor of Human Health Sciences / Kyoto University / DFAM

Exocrine pancreatic insufficiency (EPI) is a major complication of cystic fibrosis. Conventional treatment involves the replacement of pancreatic enzymes and intake of a low fat diet. However, contrary to previous therapeutic strategies, a high fat diet may be beneficial in EPI patients. The present study investigated the effects of dietary supplementation with Creon 10 000 a pancreatic enzyme preparation, in conjunction with a high-fat diet, on growth performance, digestibility and absorption of fat in a pig model of EPI by the surgical ligation of the pancreatic duct in 6 male pigs (Swedish Landrace X Yorkshire X Hampshire). Following surgery, and for the duration of the experimental period, pigs were fed a high fat diet (twice daily). The experimental period lasted for 15 days during which blood, urine and faecal samples were collected. In the last 7 days of the experimental period (days 8-14), Creon 10 000 was included in the high fat meals. Urine and faecal samples were analysed for dry matter, crude protein and fat content. Plasma was used to assess the lipaemic index and the plasma lipid profiles. Treatment with Creon 10 000 significantly increased body mass (P = 0.016) and the digestibility of dry matter, crude protein as well as the co-efficient of fat absorption were also significantly improved following treatment (P<0.05). Creon 10 000 improved the lipaemic index values and significant changes in plasma free fatty acid and triglyceride concentrations were observed but not in cholesterol or high and low density lipoproteins. This study supports previous reports that the administration of pancreatic enzyme preparations together with a high fat meal is a beneficial strategy for the nutritional management of EPI.

The effects of low carbohydrate (CHO), high fat (LCHF) diets on adaptations to high-intensity exercise have recently gained interest. Consuming a LCHF may potentially decrease the ability to use CHO during exercise and impair high-intensity exercise adaptations. Therefore, the purpose of this investigation was to examine the importance of CHO timing while consuming a LCHF diet and completing a high-intensity exercise program. Eighteen resistance trained males were randomized into two treatment groups. Both groups completed 6 weeks of a high-intensity exercise training program with the first 2 weeks serving as familiarization to resistance training (RT) 3 days per week and completing one high-intensity interval training (HIIT) session. During the final 4 weeks, participants trained 5 days per weeks, three days of RT and two days of HIIT (repeated 30 s all out sprints). All participants consumed a LCHF diet (~25%, ~25%, and ~50% of daily kilocalorie intake coming from CHO, protein, and fat). The supplemented (SUPP) group (n=9) consumed 30 g of CHO during exercise and 40 g of CHO immediately after each exercise session. The remainder of the SUPP groups daily CHO intake came outside of training. The non-supplemented (NONSUPP) group (n=9) consumed an artificially flavored placebo during exercise. The NONSUPP group had the same daily CHO intake as the SUPP group, with the only difference being CHO timing. Dependent variables measured pre-and post-training included back squat and bench press one-repetition maximums, peak oxygen consumption (V̇O2 peak), power output (Wingate test), body composition, fasted glucose, insulin, and testosterone, and gastrointestinal distress (GID) during exercise. Both groups significantly improved back squat and bench press strength, biceps thickness, absolute and relative V̇O2 peak, and power output. Respiratory exchange ratio was significantly lower and time to exhaustion significantly increased during the post V̇O2 peak test. However, there were no changes in resting glucose, insulin, and testosterone or body fat. RT and HIIT caused significant increases in GID, independent of beverage content, with no differences between training. Our results suggest that CHO timing has no impact on adaptations to exercise training, but favorable training adaptations can be made while consuming a LCHF diet.

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京都大学 / 新制・課程博士 / 博士(医学) / 甲第24200号 / 医博第4894号 / 新制||医||1061(附属図書館) / 京都大学大学院医学研究科医学専攻 / (主査)教授 長船 健二, 教授 中本 裕士, 教授 江木 盛時 / 学位規則第4条第1項該当 / Doctor of Medical Science / Kyoto University / DFAM

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