以小鼠為模式探討國人飲食中陶斯松暴露量對肥胖與腸道菌相之影響

Effects of Taiwanese dietary chlorpyrifos exposure levels on obesity and gut microbiota in normal and high-fat diet-fed mice

戴暐庭(Wei-Ting Tai)

指導教授 ： 謝淑貞

國立臺灣大學/生物資源暨農學院/食品科技研究所/碩士(2019年)

https://doi.org/10.6342/NTU201903333

摘要

代謝症候群是指血壓或空腹血糖偏高、血脂異常、腹部肥胖等許多與糖尿病和心血管疾病相關的危險因子聚集的現象，主要與生理代謝異常而產生胰島素阻抗的情形有關，而造成胰島素阻抗的原因主要為肥胖。肥胖為攝取高熱量食物以及運動量不足所導致，不過近年來也發現腸道菌相在其中扮演重要角色，而許多研究發現環境中許多物質亦有導致肥胖的疑慮，例如農藥、多氯聯苯、雙酚A等。本研究以使用量較大與使用較廣泛之殺蟲劑陶斯松作為主軸，以一般飲食與高脂飲食小鼠為模式，探討國人飲食中陶斯松的暴露量是否會影響其脂肪組織中脂質合成、代謝以及慢性發炎的反應，亦探討其對於腸道菌相的影響。在一般飲食及高脂飲食下，給予小鼠不同劑量陶斯松持續90天，結果顯示在高脂飲食下低劑量陶斯松對於皮下脂肪組織的脂質堆積較控制組有顯著影響，而腸道菌相的資訊顯示，各組之Firmicutes與Bacteroidetes ratio組間無顯著差異，低劑量和中劑量則可減少Deferribacteres的比例；低劑量亦會減少Verrucomicrobia的比例，脂多醣(lipopolysaccharide, LPS)的數據則顯示本研究所使用的劑量可能尚未影響腸道通透性，此外也以3T3-L1細胞模式探討陶斯松對脂肪細胞脂肪之影響，結果顯示低劑量陶斯松對脂肪細胞分化以及脂解作用的影響明顯高於高劑量處理，綜合上述，本研究發現低劑量的陶斯松對於動物體與脂肪細胞的影響，其相關機制仍有待後續研究進行確認。

關鍵字

農藥 ； 陶斯松 ； 肥胖 ； 腸道菌 ； 脂肪新生 ； 脂肪分解

並列摘要

Metabolic syndrome is a cluster of conditions, including increased blood pressure, high fasting blood sugar, abnormal cholesterol or triglyceride levels, excess body fat around the waist occurs together increasing your risk of heart disease and type 2 diabetes. Main reason of metabolic syndrome is insulin resistance due to metabolic abnormality. Then obesity always leads to insulin resistance. High-density caloric diets coupled with decreased physical activity as the root causes of obesity while the latest researches also regard gut microbiota as crucial factor. However, several studies have indicated the remaining chemical compound in our environment is also the possibility reason of obesity, for example pesticide, polychlorinated biphenyl (PCB), bisphenol A and so on. The aim of this study was to explore the Taiwanese dietary exposure of large usage amount, widely used pesticide-chlorpyrifos whether to affect fat synthesis and metabolism, also the grade of chronic inflammation in adipose tissue and the composition of gut microbiota by normal diet and high fat diet mice model during 90 days. Results showed that weight of inguinal subcutaneous fat in low dose chlorpyrifos group significantly higher than control group. The gut microbiota abundance ratio of phylum Firmicutes and Bacteroidetes didn’t have significantly difference between control and various doses chlorpyrifos group, but it was decreased abundance of Deferribacteres in low dose and medium dose. Abundance of Verrucomicrobia also decreased in low dose. Regardless of diet conditions, the lipopolysaccharide (LPS) concentration in serum didn’t have significantly difference between control and various doses chlorpyrifos group. It could show that dietary exposure chlorpyrifos didn’t affect the intestinal integrity. Furthermore, to investigate the effect of chlorpyrifos in adipocyte by 3T3-L1 cell model. Results showed that low dose significantly inhibited the adipogenesis and lipolysis than control group. In sum, this study found that the effects of low doses of chlorpyrifos on animal and adipocytes, the relevant mechanism remains to be confirmed by future studies.

並列關鍵字

pesticide ； chlorpyrifos ； obesity ； gut microbiota ； adipogenesis ； lipolysis

參考文獻

1.Reaven, G. M., The Metabolic Syndrome: Requiescat in Pace. Clinical chemistry 2005, 51 (6), 931-938.1.

2.Saklayen, M. G., The Global Epidemic of the Metabolic Syndrome. Current hypertension reports 2018, 20 (2), 12-12.2.

3.Blüher, M., Adipose tissue inflammation: a cause or consequence of obesity-related insulin resistance? Clinical Science 2016, 130 (18), 1603-1614.3.

4.Johnson, Andrew M. F.; Olefsky, Jerrold M., The Origins and Drivers of Insulin Resistance. Cell 2013, 152 (4), 673-684.4.

5.Lee, Y. S.; Wollam, J.; Olefsky, J. M., An Integrated View of Immunometabolism. Cell 2018, 172 (1), 22-40.5.