脑-肝轴中Δ5-和Δ6-去饱和酶的调节

Modulation of Δ5- and Δ6-desaturases in the brain-liver axis.

作者信息

Zúñiga-Hernández Jessica, Farias Camila, Espinosa Alejandra, Mercado Lorena, Dagnino-Subiabre Alexies, Campo Andrea Del, Illesca Paola, Videla Luis A, Valenzuela Rodrigo

机构信息

Biomedical Sciences Department, Faculty of Health Sciences, University of Talca, Talca, Chile.

Department of Nutrition, Faculty of Medicine, University of Chile, Santiago, Chile.

出版信息

Nutrition. 2025 Mar;131:112629. doi: 10.1016/j.nut.2024.112629. Epub 2024 Nov 12.

DOI:10.1016/j.nut.2024.112629

PMID:39642695

Abstract

OBJECTIVE

Obesity is associated with liver depletion of ω-3 polyunsaturated fatty acids (ω-3 PUFAS) promoting steatosis and inflammation, whose levels are maintained by diet or biosynthesis involving Δ-5D, Δ-6D desaturases and elongases.

METHOD

We aimed to assess Δ-5D and Δ-6D activities in liver and brain from mice fed a control diet (CD) or high-fat diet (HFD) for four to sixteen weeks.

RESULTS

HFD led to (1) an early (4 weeks) enhancement in liver Δ-5D, Δ-6D, and PPAR-α activities, without changes in oxidative stress, liver damage or fat accumulation; (2) a latter progressive loss in hepatic desaturation with insufficient compensatory increases in mRNA and protein expression, leading to ω-3 PUFA depletion, PPAR-α down-regulation reducing FA oxidation, and liver steatosis with enhancement in lipogenesis; and (3) brain ω-3 PUFA depletion after 12 to 16 weeks of HFD feeding.

CONCLUSION

In conclusion, the brain-liver axis is drastically affected by obesity in a time dependent fashion.

摘要

目的

肥胖与肝脏中ω-3多不饱和脂肪酸（ω-3 PUFAs）的消耗有关，这会促进脂肪变性和炎症，其水平可通过饮食或涉及Δ-5D、Δ-6D去饱和酶和延长酶的生物合成来维持。

方法

我们旨在评估喂食对照饮食（CD）或高脂饮食（HFD）4至16周的小鼠肝脏和大脑中的Δ-5D和Δ-6D活性。

结果

高脂饮食导致（1）肝脏Δ-5D、Δ-6D和PPAR-α活性早期（4周）增强，氧化应激、肝损伤或脂肪积累无变化；（2）随后肝脏去饱和逐渐丧失，mRNA和蛋白质表达的补偿性增加不足，导致ω-3 PUFA消耗、PPAR-α下调，从而减少脂肪酸氧化，以及肝脏脂肪变性伴脂肪生成增强；（3）高脂饮食喂养12至16周后大脑ω-3 PUFA消耗。