Role of clock genes in a mouse model for developmental origins of the metabolic syndrome

时钟基因在代谢综合征发育起源小鼠模型中的作用

• 批准号: BB/G01812X/1
• 负责人: Felino Cagampang
• 金额: $ 37.84万
• 依托单位: University of Southampton
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2009
• 资助国家: 英国
• 起止时间: 2009 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=BB%2FG01812X%2F1
• 关键词: Role; clock; genes; mouse; model

Daily, or circadian, rhythms are important in all organisms, including humans. Circadian rhythms influence nearly all aspects of physiology and behaviour, including our sleep-wake cycles, activity, feeding behaviour, cardiovascular function, body temperature and metabolism. These rhythms are generated within the body and the mechanisms that control them takes form while the baby is still in the mother's womb. Studies have shown that the diet of the mother during pregnancy is important in maintaining the health of her offspring and may also influence their susceptibility to developing obesity, diabetes and heart disease later in life. If the mother eats a healthy diet during pregnancy, one would expect the development of normal circadian rhythms of the baby's body function and metabolism, enabling the baby to cope with a healthy diet in childhood and adulthood. The risk of the person developing obesity, diabetes and heart disease later in life is very low. However, if the mother eats an unhealthy diet during pregnancy it might result in the abnormal development of circadian rhythms of body function and metabolism. This leads to disruption in sleep and activity patterns and inefficient processing of the food the baby eats. The baby is at risk of becoming heavier and fatter and will have high blood pressure in adulthood. If the baby is not brought up after birth and throughout childhood to eat a healthy diet, but eats instead a diet rich in fat, the baby's already disrupted circadian rhythms of metabolism is now not able to cope with this diet. This person is likely to become obese and risk of adult diabetes and heart disease later in life increases considerably. It is our intention of undertaking this study using a rodent model. Only by choosing an animal model is it possible to study this phenomenon, because it is necessary to change both the pre- and post natal diets and it would be unethical to undertake these changes in pregnant mothers and their babies.

日常或昼夜节律对包括人类在内的所有生物都很重要。昼夜节律几乎影响着生理和行为的所有方面，包括我们的睡眠-觉醒周期、活动、摄食行为、心血管功能、体温和新陈代谢。这些节律是在体内产生的，控制它们的机制在婴儿还在母亲子宫里的时候就形成了。研究表明，母亲在怀孕期间的饮食对维持后代的健康很重要，也可能影响他们在以后的生活中患肥胖症、糖尿病和心脏病的可能性。如果母亲在怀孕期间吃健康的饮食，人们就会期望婴儿身体功能和新陈代谢的正常昼夜节律的发展，使婴儿能够在童年和成年时期适应健康的饮食。这个人在以后的生活中患肥胖症、糖尿病和心脏病的风险非常低。然而，如果母亲在怀孕期间吃了不健康的饮食，可能会导致身体功能和新陈代谢的昼夜节律发育异常。这会导致睡眠和活动模式的中断，以及婴儿对所吃食物的低效处理。婴儿有变重变胖的危险，成年后会有高血压。如果婴儿在出生后和整个童年时期没有吃健康的饮食，而是吃富含脂肪的饮食，那么婴儿已经被打乱的昼夜节律的新陈代谢现在无法应对这种饮食。这个人很可能变得肥胖，并且在以后的生活中患成人糖尿病和心脏病的风险大大增加。我们的目的是使用啮齿动物模型进行这项研究。只有通过选择动物模型才有可能研究这种现象，因为有必要改变产前和产后的饮食，而在孕妇和她们的婴儿身上进行这些改变是不道德的。

项目成果

Variation in stability of housekeeping genes in endometrium of healthy and polycystic ovarian syndrome (PCOS) women

健康和多囊卵巢综合征（PCOS）女性子宫内膜管家基因稳定性的变化

• 发表时间: 2011
• 期刊: HUMAN REPRODUCTION
• 影响因子: 6.1
• 作者: Bruce K. D.

Developmental priming of fatty liver disease involves SIRT1 reduction, clock gene misalignment, and lipogenic transcription factor up-regulation

脂肪肝疾病的发育启动涉及 SIRT1 减少、时钟基因错位和脂肪生成转录因子上调

• 发表时间: 2011
• 作者: Bruce KD

Parental Obesity: Intergenerational Programming and Consequences

父母肥胖：代际规划及其后果

• DOI: 10.1007/978-1-4939-6386-7_12
• 发表时间: 2016
• 作者: Bruce K

Effect of pre- and postnatal high fat feeding on the 24h energy expenditure profile in the adult mouse offspring.

产前和产后高脂肪喂养对成年小鼠后代 24 小时能量消耗曲线的影响。

• 作者: Bruce KD

Altered cellular redox status, sirtuin abundance and clock gene expression in a mouse model of developmentally primed NASH.

• DOI: 10.1016/j.bbalip.2016.03.026
• 发表时间: 2016-07
• 期刊: Biochimica et biophysica acta
• 作者: Bruce KD;Szczepankiewicz D;Sihota KK;Ravindraanandan M;Thomas H;Lillycrop KA;Burdge GC;Hanson MA;Byrne CD;Cagampang FR
• 通讯作者: Cagampang FR