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J Agric Food Chem. 2017 Nov 8;65(44):9635-9646. doi: 10.1021/acs.jafc.7b03325. Epub 2017 Oct 25.

Flaxseed Oil Alleviates Chronic HFD-Induced Insulin Resistance through Remodeling Lipid Homeostasis in Obese Adipose Tissue.

Yu X1,2, Tang Y3, Liu P3, Xiao L3, Liu L3, Shen R1,2, Deng Q4,5,6, Yao P3.

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College of Food and Biological Engineering, Zhengzhou University of Light Industry , Zhengzhou 450001, China.
Henan Collaborative Innovation Center for Food Production and Safety , Zhengzhou 450001, China.
Department of Nutrition and Food Hygiene and MOE Key Laboratory of Environment and Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology , Wuhan 430030, China.
Oil Crops Research Institute, Chinese Academy of Agricultural Sciences , Wuhan 430062, China.
Hubei Key Laboratory of Lipid Chemistry and Nutrition , Wuhan 430062, China.
Key Laboratory of Oilseeds Processing, Ministry of Agriculture , Wuhan 430062, China.


Emerging evidence suggests that higher circulating long-chain n-3 polyunsaturated fatty acids (n-3PUFA) levels were intimately associated with lower prevalence of obesity and insulin resistance. However, the understanding of bioactivity and potential mechanism of α-linolenic acid-rich flaxseed oil (ALA-FO) against insulin resistance was still limited. This study evaluated the effect of FO on high-fat diet (HFD)-induced insulin resistance in C57BL/6J mice focused on adipose tissue lipolysis. Mice after HFD feeding for 16 weeks (60% fat-derived calories) exhibited systemic insulin resistance, which was greatly attenuated by medium dose of FO (M-FO), paralleling with differential accumulation of ALA and its n-3 derivatives across serum lipid fractions. Moreover, M-FO was sufficient to effectively block the metabolic activation of adipose tissue macrophages (ATMs), thereby improving adipose tissue insulin signaling. Importantly, suppression of hypoxia-inducible factors HIF-1α and HIF-2α were involved in FO-mediated modulation of adipose tissue lipolysis, accompanied by specific reconstitution of n-3PUFA within adipose tissue lipid fractions.


ATMs metabolic activation; adipose tissue lipolysis; flaxseed oil; hypoxia; insulin resistance

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