Dietary Macronutrient Composition Differentially Modulates the Remodeling of Mitochondrial Oxidative Metabolism during NAFLD.
Dietary Macronutrient Composition Differentially Modulates the Remodeling of Mitochondrial Oxidative Metabolism during NAFLD.
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DOI：
10.3390/metabo11050272
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发表时间：
2021-04-26
期刊：
影响因子：
4.1
通讯作者：
Sunny NE
中科院分区：
文献类型：
--
作者：
Kattapuram N;Zhang C;Muyyarikkandy MS;Surugihalli C;Muralidaran V;Gregory T;Sunny NE
富含脂肪和碳水化合物的饮食会加重非酒精性脂肪肝（NAFLD），其中线粒体功能障碍是其主要特征。目前尚不清楚，与高脂肪驱动的“氧化”环境相比，高碳水化合物驱动的“生脂”饮食是否对线粒体氧化重塑有不同的影响。我们假设高脂肪驱动的“氧化”环境将长期维持线粒体氧化功能，加速 NAFLD 期间的代谢功能障碍。小鼠 (C57BL/6NJ) 采用低脂（LF；10% 脂肪热量）、高脂（HF；60% 脂肪热量）或高果糖/高脂肪（HFr/HF；25% 脂肪和 34.9% 果糖热量）饮食饲养 10 周。通过使用核磁共振 (NMR) 光谱测量 D2O 中的氘掺入新合成的肝脏脂质中来确定从头脂肪生成。通过将分离的线粒体与[13C3]丙酮酸一起孵育、三羧酸（TCA）循环中间体的靶向代谢组学、氧化磷酸化（OXPHOS）的估计以及肝基因和蛋白质表达，对进食和禁食状态下的肝线粒体代谢进行了分析。与 HF 小鼠相比，HFr/HF 小鼠的从头脂肪生成更高。与我们的预期相反，HFr/HF 组在禁食后诱导了肝氧化功能。高果糖驱动的“脂肪生成”环境对线粒体氧化功能的差异诱导可能会影响肝脏胰岛素抵抗的严重程度。
Diets rich in fats and carbohydrates aggravate non-alcoholic fatty liver disease (NAFLD), of which mitochondrial dysfunction is a central feature. It is not clear whether a high-carbohydrate driven ‘lipogenic’ diet differentially affects mitochondrial oxidative remodeling compared to a high-fat driven ‘oxidative’ environment. We hypothesized that the high-fat driven ‘oxidative’ environment will chronically sustain mitochondrial oxidative function, hastening metabolic dysfunction during NAFLD. Mice (C57BL/6NJ) were reared on a low-fat (LF; 10% fat calories), high-fat (HF; 60% fat calories), or high-fructose/high-fat (HFr/HF; 25% fat and 34.9% fructose calories) diet for 10 weeks. De novo lipogenesis was determined by measuring the incorporation of deuterium from D2O into newly synthesized liver lipids using nuclear magnetic resonance (NMR) spectroscopy. Hepatic mitochondrial metabolism was profiled under fed and fasted states by the incubation of isolated mitochondria with [13C3]pyruvate, targeted metabolomics of tricarboxylic acid (TCA) cycle intermediates, estimates of oxidative phosphorylation (OXPHOS), and hepatic gene and protein expression. De novo lipogenesis was higher in the HFr/HF mice compared to their HF counterparts. Contrary to our expectations, hepatic oxidative function after fasting was induced in the HFr/HF group. This differential induction of mitochondrial oxidative function by the high fructose-driven ‘lipogenic’ environment could influence the progressive severity of hepatic insulin resistance.
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影响因子：
29.4
作者：
Lambert JE;Ramos-Roman MA;Browning JD;Parks EJ
通讯作者：
Parks EJ
影响因子：
13.5
作者：
Ishimoto, Takuji;Lanaspa, Miguel A.;Rivard, Christopher J.;Roncal-Jimenez, Carlos A.;Orlicky, David J.;Cicerchi, Christina;McMahan, Rachel H.;Abdelmalek, Manal F.;Rosen, Hugo R.;Jackman, Matthew R.;MacLean, Paul S.;Diggle, Christine P.;Asipu, Aruna;Inaba, Shinichiro;Kosugi, Tomoki;Sato, Waichi;Maruyama, Shoichi;Sanchez-Lozada, Laura G.;Sautin, Yuri Y.;Hill, James O.;Bonthron, David T.;Johnson, Richard J.
通讯作者：
Johnson, Richard J.
影响因子：
4.5
作者：
Isabel Garcia-Berumen, Claudia;Ortiz-Avila, Omar;Cortes-Rojo, Christian
通讯作者：
Cortes-Rojo, Christian
影响因子：
4.1
作者：
Green, Charlotte J.;Pramfalk, Camilla;Hodson, Leanne
通讯作者：
Hodson, Leanne
影响因子：
6.5
作者：
Duarte, Joao A. G.;Carvalho, Filipa;Burgess, Shawn C.
通讯作者：
Burgess, Shawn C.