Effects of distinct n-6 to n-3 polyunsaturated fatty acid ratios on insulin resistant and AD-like phenotypes in high-fat diets-fed APP/PS1 mice

被引:8
作者
Ma, Xiaojun [1 ]
Guo, Yujie [1 ]
Xu, Jingjing [1 ]
Wang, Xixiang [1 ]
Dong, Shengqi [1 ]
Gao, Yanyan [1 ]
Van Halm-Lutterodt, Nicholas [3 ]
Yuan, Linhong [1 ,2 ]
机构
[1] Capital Med Univ, Sch Publ Hlth, Dept Nutr & Food Hyg, Beijing, Peoples R China
[2] Capital Med Univ, Beijing Key Lab Environm Toxicol, Beijing, Peoples R China
[3] Brown Univ, Sch Profess Studies, Providence, RI 02912 USA
基金
中国国家自然科学基金;
关键词
High-fat diet; Insulin resistance; N-6/n-3 PUFA ratio; AD-like pathology; APP/PS1; mice; GROWTH-FACTOR EXPRESSION; BLOOD-CELL MEMBRANES; ALZHEIMERS-DISEASE; GLUCOSE TRANSPORTERS; COGNITIVE DECLINE; AMYLOID-BETA; MOUSE MODEL; BRAIN; ACCUMULATION; MECHANISMS;
D O I
10.1016/j.foodres.2022.112207
中图分类号
TS2 [食品工业];
学科分类号
0832 ;
摘要
Type 2 diabetes mellitus (T2DM) and Alzheimer's disease (AD) are prevalent diseases with similar pathophysiological characteristics and genetic predispositions. Polyunsaturated fatty acids (PUFAs) are essential in maintaining normal brain function. However, little is known about the effect of dietary n-6/n-3 PUFA ratio on AD-like pathology, particularly in high-fat diet (HFD)-fed AD model mice. In the present study, the APP/PS1 mice were fed with 60 % HFD for 3.5 months to induce insulin resistance. After that, 45 % HFD with various n-6/ n-3 PUFA ratios (n-6/n-3 = 1:1, 5:1 or 16:1) was applied for an additional 3.5 months of treatment. The behavior of mice was observed using the water maze after dietary intervention. The animals were euthanized after behavioral testing, and serum and tissue samples were collected for biochemical, histological, and pathological tests and evaluation. HFD caused insulin resistance, increased serum IL-6 and TNF- alpha levels, cortical soluble A beta(1-40), A beta(1- 42) content, and cortical n-6/n-3 PUFA ratio in APP/PS1 mice. Increased APP and BACE1 protein expression and p-IR/IR ratio but decreased pro-inflammatory cytokines mRNA expression was detected in the cortex of 60 % HFD-fed APP/PS1 mice. N-3 PUFAs-rich diet (n-6/n-3 = 1:1) alleviated insulin resistance and hyperlipidemia caused by 60 % HFD. Cortical soluble A beta(1- 40) and A beta(1- 42) contents, as well as the expression of cortical APP, GLUT1, GLUT3, insulin metabolism-related molecules, and NF-kappa B pathway downstream proinflammatory cytokines, were found to be n-6/n-3 PUFAs ratio-dependent, indicating that dietary n-6/n-3 PUFA ratio plays a critical role in modifying the responses of serum inflammatory cytokines, AD pathology, cortical n-6/n-3 PUFAs ratio, insulin signaling, and neuroinflammation to HFD treatment.
引用
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页数:13
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