Dietary n-3 long-chain polyunsaturated fatty acids upregulate energy dissipating metabolic pathways conveying anti-obesogenic effects in mice.
Dietary n-3 long-chain polyunsaturated fatty acids upregulate energy dissipating metabolic pathways conveying anti-obesogenic effects in mice.
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DOI：
10.1186/s12986-018-0291-x
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发表时间：
2018
影响因子：
4.5
通讯作者：
Bader BL
中科院分区：
文献类型：
--
作者：
Worsch S;Heikenwalder M;Hauner H;Bader BL
我们之前在饮食诱导肥胖 (DIO) 小鼠模型中报道了与 n-3 长链多不饱和脂肪酸 (LCPUFA) 相关的抗肥胖和抗炎作用。使用两种等热量高脂肪饮食（HFD；48 kJ% 脂肪）、HFD (HF) 和富含 n-3 LCPUFA 的 HFD (HF/n-3) 以及对照饮食（C；13 kJ% 脂肪）。然而，其根本机制在很大程度上仍不清楚。在这里，我们评估了脂肪量的减少是否反映了 n-3 LCPUFA 诱导的肠道、肝脏和肩胛间棕色脂肪组织 (iBAT) 脂质代谢的表达变化，以及 iBAT 生热能力的增加。对于 HF/n-3，饱和和单不饱和脂肪酸被 n-3 LCPUFA 二十碳五烯酸和二十二碳六烯酸部分取代，与 HF (13.5) 和 C (9.85) 的不平衡比率相比，实现了平衡的 n-6/n-3 PUFA 比率 (0.84)。对饲喂特定大豆/棕榈油饮食 12 周的雄性 C57BL/6 J 小鼠的肠、肝脏和 iBAT 进行了进一步分析。进行了基因和蛋白质表达分析、免疫组织化学和代谢相互作用的相关分析。与 HF 和 C 相比，我们的分析表明 HF/n-3 小鼠的从头脂肪生成 (DNL) 显着减少和/或肝脏和肠道脂肪酸氧化（ω-氧化和过氧化物酶体 β-氧化）增加。对于 iBAT，HF/n-3 的产热潜力增强，这与解偶联蛋白 1 和参与线粒体生物发生的基因的表达上调一致。此外，观察到脂肪酸的供应和氧化能力较高，表达和相关分析表明能量代谢和三酰甘油（TAG）的无效循环的协调调节。此外，HF/n-3显着增加了抗炎巨噬细胞和嗜酸性粒细胞的数量，并显着提高了活化的AMP激活蛋白激酶α（AMPKα）、过氧化物酶体增殖物激活受体α（PPARα）和成纤维细胞生长因子21（FGF21）的水平。我们的数据表明，通过将转录调控途径、AMPKα和FGF21作为潜在介质，HF/n-3激活了效率较低的能量产生途径，例如过氧化物酶体β-氧化，在诱导TAG无效循环时增加了ATP消耗，并另外增加了iBAT的生热和氧化潜力。因此，我们认为 n-3 LCPUFA 是上调能量耗散代谢途径的有效诱导剂，从而在小鼠中发挥抗肥胖作用。本文的在线版本 (10.1186/s12986-018-0291-x) 包含补充材料，可供授权用户使用。
We previously reported on the anti-obesogenic and anti-inflammatory effects associated with n-3 long-chain polyunsaturated fatty acids (LCPUFA) in our diet-induced obesity (DIO) mouse model. Two isocaloric high-fat diets (HFDs; 48 kJ% fat), HFD (HF) and n-3 LCPUFA-enriched HFD (HF/n-3), and a control diet (C; 13 kJ% fat) were used. The underlying mechanisms however have largely remained unclear. Here, we assessed whether the reduced fat mass reflected n-3 LCPUFA-induced expression changes in lipid metabolism of the intestine, liver, and interscapular brown adipose tissue (iBAT), as well as increased iBAT thermogenic capacity. For HF/n-3, saturated and monounsaturated fatty acids were partially substituted by n-3 LCPUFA eicosapentaenoic acid and docosahexaenoic acid to achieve a balanced n-6/n-3 PUFA ratio (0.84) compared to the unbalanced ratios of HF (13.5) and C (9.85). Intestine, liver and iBAT from male C57BL/6 J mice, fed defined soybean/palm oil-based diets for 12 weeks, were further analysed. Gene and protein expression analyses, immunohistochemistry and correlation analyses for metabolic interactions were performed. Compared to HF and C, our analyses suggest significantly diminished de novo lipogenesis (DNL) and/or increased hepatic and intestinal fatty acid oxidation (ω-oxidation and peroxisomal β-oxidation) in HF/n-3 mice. For iBAT, the thermogenic potential was enhanced upon HF/n-3 consistent with upregulated expression for uncoupling protein-1 and genes involved in mitochondrial biogenesis. In addition, a higher capacity for the supply and oxidation of fatty acids was observed and expression and correlation analyses indicated a coordinated regulation of energy metabolism and futile cycling of triacylglycerol (TAG). Moreover, HF/n-3 significantly increased the number of anti-inflammatory macrophages and eosinophils and significantly enhanced the levels of activated AMP-activated protein kinase α (AMPKα), peroxisome proliferator-activated receptor α (PPARα) and fibroblast growth factor 21 (FGF21). Our data suggest that by targeting transcriptional regulatory pathways, AMPKα, and FGF21 as potential mediators, HF/n-3 activated less efficient pathways for energy production, such as peroxisomal β-oxidation, increased ATP consumption upon the induction of futile cycling of TAG, and additionally increased the thermogenic and oxidative potential of iBAT. Therefore, we consider n-3 LCPUFA as the potent inducer for upregulating energy dissipating metabolic pathways conveying anti-obesogenic effects in mice. The online version of this article (10.1186/s12986-018-0291-x) contains supplementary material, which is available to authorized users.
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影响因子：
82.9
作者：
Fischer K;Ruiz HH;Jhun K;Finan B;Oberlin DJ;van der Heide V;Kalinovich AV;Petrovic N;Wolf Y;Clemmensen C;Shin AC;Divanovic S;Brombacher F;Glasmacher E;Keipert S;Jastroch M;Nagler J;Schramm KW;Medrikova D;Collden G;Woods SC;Herzig S;Homann D;Jung S;Nedergaard J;Cannon B;Tschöp MH;Müller TD;Buettner C
通讯作者：
Buettner C
影响因子：
30.8
作者：
通讯作者：
--
影响因子：
5.6
作者：
Dossi, Camila G.;Tapia, Gladys S.;D'Espessailles, Amanda
通讯作者：
D'Espessailles, Amanda
影响因子：
8.1
作者：
Dahlhoff C;Worsch S;Sailer M;Hummel BA;Fiamoncini J;Uebel K;Obeid R;Scherling C;Geisel J;Bader BL;Daniel H
通讯作者：
Daniel H
DOI：
10.1073/pnas.1006962107
发表时间：
2010-07-13
影响因子：
11.1
作者：
Chau, Mary D. L.;Gao, Jiaping;Gromada, Jesper
通讯作者：
Gromada, Jesper