Short-term effects of overfeeding on metabolic risk in humans

过度喂养对人类代谢风险的短期影响

• 批准号: nhmrc : 427639
• 负责人: A/Pr Leonie Heilbronn
• 金额: $ 27.82万
• 依托单位: Garvan Institute of Medical Research
• 依托单位国家: 澳大利亚
• 项目类别: NHMRC Project Grants
• 财政年份: 2007
• 资助国家: 澳大利亚
• 起止时间: 2007-01-01 至 2009-12-31
• 项目状态: 已结题
• 来源: https://researchdata.edu.au/short-term-effects-risk-humans/81429
• 关键词: Short; term; effects; overfeeding; metabolic

The prevalence of obesity is rapidly increasing in Australia and other parts of the world. Obesity is closely associated with insulin resistance and plays a role in the development of type 2 diabetes. However, the effects of short-term periods of over nutrition in humans remain unclear. In the proposed study, we will investigate the effects of short-term weight gain by high fat feeding in lean subjects, in subjects who are overweight and in subjects who are genetically more likely to develop diabetes (due to strong family history). The aims are to distinguish physiological and endocrine characteristics of individuals who store more fat in response to overfeeding. We will identify differences between these individuals and whether they have defects in upregulating machinery involved in fat oxidation and energy production in skeletal muscle that may help them adapt during to energy excess. We will look for changes in type 2 diabetes risk and we will have the potential to identify defects in factors that are involved in this response. We will also re-examine indivudals again after calorie restriction and weight loss. We also plan to confirm the role of the candidate genes involved in fat oxidation that have been identifieid in human studies by in vivo gene transfer technology in rodents. This study will determine whether overweight and lean subjects behave similarly when faced with an overfeeding challenge. We expect that individuals with a genetic predisposition for T2DM will become more IR, due to metabolic inflexibility and a decreased ability to upregulate machinery involved in fatty acid oxidation and mitochondrial function. By characterising the physiological and endocrine responses to overfeeding, we will establish quantifiable markers allowing us to distinguish those at risk and identify new targets for pharmacological or lifestyle intervention.

在澳大利亚和世界其他地区，肥胖症的流行率正在迅速上升。肥胖与胰岛素抵抗密切相关，并在2型糖尿病的发展中发挥作用。然而，短期营养过剩对人类的影响尚不清楚。在这项拟议的研究中，我们将调查高脂肪喂养对瘦受试者、超重受试者和遗传上更容易患糖尿病的受试者(由于有很强的家族病史)的短期体重增加的影响。其目的是区分因过度进食而储存更多脂肪的个体的生理和内分泌特征。我们将确定这些个体之间的差异，以及他们是否在参与骨骼肌脂肪氧化和能量产生的上调机制方面存在缺陷，这可能有助于他们在适应能量过剩的过程中。我们将寻找2型糖尿病风险的变化，我们将有可能确定参与这一反应的因素中的缺陷。我们还将在限制卡路里和减肥后再次对个体进行检查。我们还计划通过在啮齿动物体内的基因转移技术来确认参与脂肪氧化的候选基因在人类研究中的作用。这项研究将确定超重和苗条的受试者在面对过度进食挑战时的表现是否相似。我们预计，具有T2 DM遗传易感性的个体将变得更加IR，这是由于代谢缺乏灵活性，以及上调涉及脂肪酸氧化和线粒体功能的机械的能力降低。通过表征对过度喂养的生理和内分泌反应，我们将建立可量化的标记物，使我们能够区分处于危险中的人，并确定药物或生活方式干预的新靶点。