血浆脂质谱及膳食特征对体脂积累和分布的影响：基于西北自然人群队列的研究

As the definition of obesity, adiposity accumulation, particularly at abdomen, is a leading component in the pathogenesis of obesity related chronic metabolic diseases. With the obesity prevalence growing more rapidly in west China, the substantial influences of their typical dietary patterns, lifestyle, and environment features were not well-understood. This project will be a multi-stage study based on data and samples from an established prospective cohort study, the China Northwest Cohort (CNC) study. Firstly, description analyses will be conducted for the obesity phenotypes and body fat distribution of the multi-ethnic population in the CNC study, and potential risk factors regarding dietary pattern and lifestyle features will be identified. Secondly, taking the advantage of cohort resurvey, and untargeted lipidomic approach (high throughput results with maximum identification of all the lipid molecules in biofluid), feature metabolites specifically predicting body fat accumulation and distribution change will be identified with a nested case-control design. Meanwhile, possible underling mechanisms and pathways are promisingly to be explored, with high-throughput results of lipidomic profile. Furthermore, sub-population-specific prediction models based on lipidomic profile will be established for adiposity accumulation and distribution. Our study results will provide novo insight into the extent to which dietary pattern may have substantially influenced the adiposity accumulation, and will be helpful to build up evidence-based screening strategies for people in high risk of obesity and related metabolic disease among northwest multi-ethnic population.

脂肪积累是肥胖的本质，而腹部脂肪积累是诸多慢病发生的早期诱因。我国西部地区肥胖率增速高于中东部，该区域人口特征及生活环境独特多样，长期膳食和生活方式如何影响肥胖发生的本质—脂肪积累，还未见详细研究报道。本项目拟依托于已建立的西北多民族自然人群队列数据和生物样本，在对多民族居民的肥胖表型和体脂分布特征及其膳食、生活方式和环境影响因素进行梳理的基础上，在队列重复调查中，以脂肪过多积累和腹型肥胖为主要结局，采用巢式病例对照设计，利用非靶向脂质组学技术，明确影响体脂积累和分布改变的特征性血浆脂质谱及代谢通路分子标记，结合传统风险因素，探讨影响该地区居民脂肪积累及分布规律的机制，并将建立不同亚人群体脂积累和分布预测模型。本研究将为揭示长期膳食习惯下的脂肪积累规律提供基于脂质组学的数据支持，为我国西北多民族居民肥胖相关代谢异常的高危人群早期精准筛查提供科学依据，从而为减轻该区域慢病负担做贡献。

脂肪积累是肥胖的本质，而腹部脂肪积累是诸多慢病发生的早期诱因。我国西北地区人口特征及生活环境独特多样，具有鲜明的膳食习惯特征，影响该地区居民肥胖表型的关键膳食特征是什么，还未见详细研究报道。本项目依托于西北自然人群队列数据和生物样本，梳理了该地区人群的肥胖表型特点，发现新疆、青海地区居民体脂过多和腹型肥胖占比最高，与偏好米饭主食相比，偏好面食与体脂过多积累、腹型肥胖风险正相关。在西北居民中，采用病例对照等设计，利用非靶向/广泛靶向脂质组学技术，明确了体脂过多积累与腹型肥胖的特征性血浆脂质谱，利用脂质组数据识别了主要代谢通路，主要有磷脂合成、鞘脂代谢、线粒体电子传递链、三羧酸循环、脂肪酸合成等，发现血浆代谢物对于碳酸饮料及大米过多摄入与腹型肥胖的关联有显著的介导作用。此外，利用一项营养减肥随机对照试验的血浆代谢组数据，发现基于血浆代谢物数据能更好地预测减肥中体脂降低。本研究为揭示长期膳食习惯下的脂肪积累规律提供了基于脂质组学的数据支持，为我国西北居民肥胖表型的识别、膳食危险因素及精准干预策略提供科学依据。