Odd chain fatty acid metabolism in mice after a high fat diet.
Odd chain fatty acid metabolism in mice after a high fat diet.
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DOI：
10.1016/j.biocel.2021.106135
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发表时间：
2022-03
期刊：
影响因子：
--
通讯作者：
Griffiths HR
中科院分区：
文献类型：
--
作者：
Ampong I;John Ikwuobe O;Brown JEP;Bailey CJ;Gao D;Gutierrez-Merino J;Griffiths HR
流行病学研究表明，奇数链饱和脂肪酸（FA：C15：0和C17：0）的循环水平较高与代谢性疾病的风险较低相关。这些奇数链饱和脂肪酸 (OCSFA) 是通过过氧化物酶体中的 α-氧化、从头脂肪生成、饮食和肠道微生物群产生的。尽管浓度较低，但它们作为降低代谢疾病风险的潜在靶点引起了人们的兴趣。为了确定 OCSFA 是否受到肥胖饮食的影响，我们研究了高膳食脂肪摄入是否会影响产生 OCSFA 的肠道微生物群、肝脏脂质代谢基因和循环 OCSFA 的频率。测定喂养标准饲料或高脂肪饮食（HFD；60% 卡路里为脂肪）4 周和 12 周的无病原体 SPF C57BL/6J 小鼠的肝脏和血清中的 FA 浓度。通过气相色谱-质谱法分析死后小鼠肝脏的脂肪沉积情况，分析 FA 的组成，并通过 qPCR 分析脂质代谢基因脂肪酸去饱和酶 2 (FADS2)、硬脂酰辅酶 A 去饱和酶 1 (SCD1)、长链脂肪酸家族成员 6 延伸 (ELOVL6) 和 2-羟酰辅酶A 裂解酶 1 (HACL)。通过 16S RNA 测序分析回肠粪便颗粒中的肠道微生物群。在 HFD 喂养的 SPF 小鼠中，4 周后观察到血清和肝脏 C15:0 (>50%；P<0.05) 和肝脏 C17:0 (>35%；P<0.05) 显着减少，同时肝脏脂肪积累。此外，SPF小鼠经HFD治疗后，肝脏基因表达（HACL1、ELOVL6、SCD1和FADS2）降低（>50%；P<0.05），产生C3:0的有益肠道细菌（如阿克曼氏菌、乳杆菌、双歧杆菌）的相对丰度也降低。总之，高膳食脂肪摄入量会降低血清和肝脏 OCSFA、产生 OCSFA 的肠道微生物群，并与肝脏脂质代谢受损相关。需要进一步的研究来确定 OCSFA 和产生 C3:0 的肠道细菌是否对对抗代谢疾病有任何有益作用。已知肝脏和微生物代谢会影响奇数链脂肪酸 (OCFA) 水平。高脂肪饮食 (HFD) 降低了小鼠的血浆 C15:0 和肝脏 C15:0 和 C17:0。 HFD 喂养的小鼠 HACL1、ELOVL6、SCD1 和 FADS2 表达较低，并且肝脏脂肪积累。 HFD 后阿克曼氏菌、乳杆菌、双歧杆菌的相对丰度降低。 HFD 降低了 OCFA 水平、产生 OCFA 的肠道微生物群和肝脏 FA 代谢。
Epidemiological studies show that higher circulating levels of odd chain saturated fatty acids (FA: C15:0 and C17:0) are associated with lower risk of metabolic disease. These odd chain saturated fatty acids (OCSFA) are produced by α-oxidation in peroxisomes, de novo lipogenesis, from the diet and by gut microbiota. Although present at low concentrations, they are of interest as potential targets to reduce metabolic disease risk. To determine whether OCSFA are affected by obesogenic diets, we have investigated whether high dietary fat intake affects the frequency of OCSFA-producing gut microbiota, liver lipid metabolism genes and circulating OCSFA. FA concentrations were determined in liver and serum from pathogen-free SPF C57BL/6 J mice fed either standard chow or a high fat diet (HFD; 60% calories as fat) for four and twelve weeks. Post-mortem mouse livers were analysed histologically for fat deposition by gas chromatography–mass spectrometry for FA composition and by qPCR for the lipid metabolic genes fatty acid desaturase 2 (FADS2), stearoyl CoA desaturase 1 (SCD1), elongation of long-chain fatty acids family member 6 (ELOVL6) and 2-hydroxyacyl-CoA lyase 1 (HACL). Gut microbiota in faecal pellets from the ileum were analysed by 16S RNA sequencing. A significant depletion of serum and liver C15:0 (>50%; P < 0.05) and liver C17:0 (>35%; P < 0.05) was observed in HFD-fed SPF mice in parallel with hepatic fat accumulation after four weeks. In addition, liver gene expression (HACL1, ELOVL6, SCD1 and FADS2) was lower (>50%; P < 0.05) and the relative abundance of beneficial C3:0-producing gut bacteria such as Akkermansia, Lactobacillus, Bifidobacterium was lower after HFD in SPF mice. In summary, high dietary fat intake reduces serum and liver OCSFA, OCSFA-producing gut microbiota and is associated with impaired liver lipid metabolism. Further studies are required to identify whether there is any beneficial effect of OCSFA and C3:0-producing gut bacteria to counter metabolic disease. Liver and microbiota metabolism are known to affect odd chain fatty acid (OCFA)levels. A high fat diet (HFD) lowered plasma C15:0 and liver C15:0 and C17:0 in mice. HFD-fed mice expressed lower HACL1, ELOVL6, SCD1 and FADS2, and accumulated liver fat. Relative abundance of Akkermansia, Lactobacillus, Bifidobacterium was lower after HFD. HFD reduced OCFA levels, OCFA-producing gut microbiota and hepatic FA metabolism.
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DOI：
10.1016/j.bbrc.2016.10.031
发表时间：
2016-11-11
影响因子：
3.1
作者：
Li, Zhipeng;Jin, Hui;Ji, Geun Eog
通讯作者：
Ji, Geun Eog
DOI：
10.1073/pnas.1219451110
发表时间：
2013-05-28
影响因子：
11.1
作者：
Everard, Amandine;Belzer, Clara;Cani, Patrice D.
通讯作者：
Cani, Patrice D.
影响因子：
3.3
作者：
Gentile, C. L.;Weir, T. L.;Foster, M. T.
通讯作者：
Foster, M. T.
DOI：
10.3390/molecules20022425
发表时间：
2015-01-30
期刊：
Molecules (Basel, Switzerland)
影响因子：
--
作者：
Jenkins B;West JA;Koulman A
通讯作者：
Koulman A
影响因子：
3.6
作者：
Gao, Dan;Griffiths, Helen R.;Bailey, Clifford J.
通讯作者：
Bailey, Clifford J.