京都大学 / 新制・課程博士 / 博士(農学) / 甲第24109号 / 農博第2514号 / 新制||農||1093(附属図書館) / 学位論文||R4||N5400(農学部図書室) / 京都大学大学院農学研究科応用生物科学専攻 / (主査)教授 佐藤 健司, 教授 菅原 達也, 准教授 木下 政人 / 学位規則第4条第1項該当 / Doctor of Agricultural Science / Kyoto University / DGAM

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<p>A high-fat diet can adversely affect bone mechanical properties, but it is unknown how these changes affect bone adaptation. Bone adaptation occurs in response to strain-related mechanisms, and strain in the bone is affected by the size and mechanical properties of the bone.The purpose of this study was to compare the strain during loading in femurs from rats fed a high-fat (HF) or normal control (NC) diet. At 3 weeks of age, male and female Wistar rats were randomly assigned to receive a NC (NC–17% fat; N=8 per gender) or HF diet (HF–41% fat; N=8 per gender) until termination (39 weeks of age). Right femurs were loaded <em>ex vivo</em> in 3-point bending to physiologic levels and mechanical strain was measured. The mechanical properties of the left femurs were determined by 3-point bend tests to failure. The dietary effects were limited in both genders. Femoral cross-sectional area properties (bone area, moment of inertia), determined from µCT scans, were significantly greater in HF femurs vs. NC for males and females. Elastic modulus was calculated from strain and deformation data and no dietary effects were seen in either gender. At the applied loads, despite significantly larger cross-sectional area properties in the HF femurs, there was no significant difference in strain between HF and NC femurs for either gender. It appears that adaptive modeling occurs during growth in the HF bones to target a predetermined level of strain to preserve bone structural integrity.</p> / Master of Applied Science (MASc)

Adult exposure to high fat diet (HFD) has been linked to increased risk of musculoskeletal, cardiovascular, and metabolic diseases; however, the contribution of gestational HFD to elevated oxidative stress (OS), perinatal cardiovascular, skeletal, and metabolic dysfunction as well as long-term effects on adult offspring are incompletely understood. Pathophysiologic mechanisms linking gestational HFD, OS, and insulin resistance to perinatal development and adult-onset chronic diseases are explored in the present study, and maternal antioxidant (quercetin) is offered as a potential preventive dietary supplement to reduce fetal and maternal sequelae of HFD. Female C57BL/6 mice were fed "cafeteria-style" HFD (including 32.1% saturated fat to mimic a typical fast food menu) with or without quercetin for one month prior to conception, and throughout gestation. HFD dams developed gestational diabetes with significantly increased placental OS and vasculopathy. Neonates were smaller at birth than age-matched controls, and surviving offspring developed type 2 diabetes, hypertension and osteoporosis during adulthood, despite having been fed healthy diet throughout their postnatal life. Additional measures of bone using three-dimensionally reconstructed computed tomographic image analysis (microCT) revealed microarchitectural changes of bone at birth, and at 6 and 12 months postnatally. Fetuses from HFD dams displayed diminished bone mineral density (BMD) and disrupted endochondral and intramembranous ossification with significantly shortened distal limb lengths, as compared to offspring of standard rodent chow dams. Skeletal malformation persisted into adulthood despite the fact that both control and HFD offspring were fed conventional rodent chow throughout postnatal life. The offspring gestationally exposed to HFD showed significant decreased femoral BMD at 6 months of age and dysregulation of distal femoral trabecular architecture at 12 months of age, indicating development of osteoporosis. We were able to reduce incidence of placental vasculopathy, fetal maldevelopment and adult-onset type 2 diabetes, hypertension and osteoporosis with concurrent maternal quercetin supplementation during pregnancy. Collectively, these data suggested that maternal HFD increases placental OS and vascular damage during pregnancy, which are associated with fetal malformation and elevated adult-onset multisystemic chronic diseases. Maternal quercetin supplementation must be further explored as a potential dietary intervention for improved placental integrity, fetal development and lifelong health. / Ph. D.