High fat feeding induces hepatic fatty acid elongation in mice.
High fat feeding induces hepatic fatty acid elongation in mice.
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DOI：
10.1371/journal.pone.0006066
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发表时间：
2009-06-26
期刊：
影响因子：
3.7
通讯作者：
Reijngoud DJ
中科院分区：
文献类型：
--
作者：
Oosterveer MH;van Dijk TH;Tietge UJ;Boer T;Havinga R;Stellaard F;Groen AK;Kuipers F;Reijngoud DJ
高脂饮食促进肝脏脂质蓄积。巧合的是，这些饮食也诱导啮齿动物肝脏中的脂肪生成基因表达。这些基因的高表达是否实际上导致通过体内从头脂肪生成途径的通量增加尚未得到证实。为了探究这一明显的悖论，我们量化了喂食食物、高脂肪或富含n-3多不饱和脂肪酸（PUFA）的高脂肪饮食的C57 Bl/6 J小鼠的从头脂肪生成。一种新的方法的基础上质量同位素分布分析（MIDA）的1- 13 C醋酸输注后，应用于同时确定从头脂肪生成，脂肪酸延长以及胆固醇合成。此外，我们测量了极低密度脂蛋白-甘油三酯（VLDL-TG）的生产率。高脂喂养促进肝脏脂质积累，并诱导脂肪和胆固醇基因的表达相比，饲料喂养的小鼠：基因表达的诱导被发现转化为增加油酸合成。有趣的是，在喂食高脂饲料的小鼠中，这种较高的脂肪生成通量（油酸为+74 µg/g/h）主要是由于未标记棕榈酸酯的肝脏延长（+66 µg/g/h）而不是从头合成棕榈酸酯的延长。此外，胆固醇合成分数增加，即对照组和高脂肪喂养动物分别为5.8±0.4%和8.1±0.6%。肝脏VLDL-TG的产生不受高脂喂养的影响。鱼油部分替代饱和脂肪完全逆转了高脂喂养的脂肪生成作用：肝脏脂肪生成和胆固醇生成基因表达水平以及脂肪酸和胆固醇合成率正常化。高脂喂养通过链延长和随后的去饱和而不是从头合成诱导小鼠肝脏脂肪酸合成，而VLDL-TG输出不受影响。鱼油抑制脂肪生成通量可预防高脂饮食诱导的小鼠肝脏脂肪变性。
High-fat diets promote hepatic lipid accumulation. Paradoxically, these diets also induce lipogenic gene expression in rodent liver. Whether high expression of these genes actually results in an increased flux through the de novo lipogenic pathway in vivo has not been demonstrated. To interrogate this apparent paradox, we have quantified de novo lipogenesis in C57Bl/6J mice fed either chow, a high-fat or a n-3 polyunsaturated fatty acid (PUFA)-enriched high-fat diet. A novel approach based on mass isotopomer distribution analysis (MIDA) following 1-13C acetate infusion was applied to simultaneously determine de novo lipogenesis, fatty acid elongation as well as cholesterol synthesis. Furthermore, we measured very low density lipoprotein-triglyceride (VLDL-TG) production rates. High-fat feeding promoted hepatic lipid accumulation and induced the expression of lipogenic and cholesterogenic genes compared to chow-fed mice: induction of gene expression was found to translate into increased oleate synthesis. Interestingly, this higher lipogenic flux (+74 µg/g/h for oleic acid) in mice fed the high-fat diet was mainly due to an increased hepatic elongation of unlabeled palmitate (+66 µg/g/h) rather than to elongation of de novo synthesized palmitate. In addition, fractional cholesterol synthesis was increased, i.e. 5.8±0.4% vs. 8.1±0.6% for control and high fat-fed animals, respectively. Hepatic VLDL-TG production was not affected by high-fat feeding. Partial replacement of saturated fat by fish oil completely reversed the lipogenic effects of high-fat feeding: hepatic lipogenic and cholesterogenic gene expression levels as well as fatty acid and cholesterol synthesis rates were normalized. High-fat feeding induces hepatic fatty acid synthesis in mice, by chain elongation and subsequent desaturation rather than de novo synthesis, while VLDL-TG output remains unaffected. Suppression of lipogenic fluxes by fish oil prevents from high fat diet-induced hepatic steatosis in mice.
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影响因子：
3.9
作者：
Gibbons, GF;Wiggins, D;Hebbachi, AM
通讯作者：
Hebbachi, AM
影响因子：
4.1
作者：
Jung, HR;Turner, SM;Hellerstein, MK
通讯作者：
Hellerstein, MK
影响因子：
4.8
作者：
Li, Zheng Zheng;Berk, Michael;Feldstein, Ariel E.
通讯作者：
Feldstein, Ariel E.
DOI：
10.1016/0005-2760(95)00006-x
发表时间：
1995-04-28
期刊：
BIOCHIMICA ET BIOPHYSICA ACTA-LIPIDS AND LIPID METABOLISM
影响因子：
--
作者：
LIN, YG;SMIT, MJ;KUIPERS, F
通讯作者：
KUIPERS, F
影响因子：
2.8
作者：
Davidson, Michael H.
通讯作者：
Davidson, Michael H.