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Flaxseed Oil Attenuates Hepatic Steatosis and Insulin Resistance in Mice by Rescuing the Adaption to ER Stress
- Yu, Xiao, Deng, Qianchun, Tang, Yuhan, Xiao, Lin, Liu, Liegang, Yao, Ping, Tang, Hu, Dong, Xuyan
- Journal of agricultural and food chemistry 2018 v.66 no.41 pp. 10729-10740
- animal models, biochemical pathways, dose response, endoplasmic reticulum, fatty liver, high fat diet, humans, inflammation, insulin receptors, insulin resistance, linseed oil, lipid composition, lipid metabolism disorders, liver, mice, mitogen-activated protein kinase, non-specific serine/threonine protein kinase, noninsulin-dependent diabetes mellitus, omega-3 fatty acids, phosphorylation, tyrosine, unfolded protein response
- Increasing evidence has demonstrated the benefits of α-linolenic acid-rich flaxseed oil (ALA-FO) against lipid metabolism abnormality in both rodent models and humans. However, the metabolic response of FO to insulin resistance and type 2 diabetes is still inconsistent. This study aimed to explore the effect of FO on chronic high fat diet (HFD)-induced hepatic steatosis, insulin resistance, and inflammation, mainly focusing on hepatic n-3 fatty acid remodeling and endoplasmic reticulum (ER) unfolded protein response. The results showed that lard-based HFD feeding for 16 weeks (60% fat-derived calories) induced whole-body insulin resistance, lipid profile abnormality, and inflammation in mice, which was alleviated by FO in a dose-dependent manner. Moreover, FO effectively improved hepatic steatosis and insulin resistance in mice by modulating the specific location of ALA and its long-chain n-3 fatty acids across hepatic lipid fractions and enhancing insulin-stimulated phosphorylation of hepatic insulin receptor subtract-1 (IRS-1) tyrosine 632 and protein kinase B (AKT) (p < 0.05). Importantly, the differential depositions of ALA and its long-chain n-3 fatty acids in plasma and ER membranes were observed, concomitant with the rescued ER unfolded protein response and Jun N-terminal kinase (JNK) signaling in mice liver.