A High-Fat Diet Disrupts Nerve Lipids and Mitochondrial Function in Murine Models of Neuropathy.
A High-Fat Diet Disrupts Nerve Lipids and Mitochondrial Function in Murine Models of Neuropathy.
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DOI：
10.3389/fphys.2022.921942
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发表时间：
2022
影响因子：
4
通讯作者：
中科院分区：
文献类型：
--
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随着前驱糖尿病和2型糖尿病（T2 D）的患病率在全球范围内持续增加，伴随的并发症也在增加。最常见的并发症，周围神经病变（PN），是一个复杂的过程，仍然不完全了解。血脂异常是糖尿病前期和T2 D患者PN的一个新风险因素，表明过量脂质损害外周神经;然而，导致PN的确切脂质变化尚不清楚。为了确定与PN相关的特定脂质变化，我们进行了一项非靶向脂质组学分析，比较了高脂饮食（HFD）喂养对三种小鼠（BL 6、BTBR和BKS）血浆、肝脏和外周神经中脂质的影响。HFD喂养引发了不同的品系和组织特异性脂质变化，这与BL 6小鼠中的PN相关，而不是代谢功能障碍和PN的不太稳健的鼠模型（BTBR和BKS小鼠）。BL 6小鼠神经内的中性脂质、磷脂、溶血磷脂和缩醛磷脂均发生显著变化。鞘磷脂（SM）和溶血磷脂酰乙醇胺（LPE）是HFD BL 6坐骨神经与其他菌株（BTBR和BKS）相比所特有的两种脂质物质。血浆和肝脏脂质显着改变，在所有小鼠品系喂食HFD独立的PN状态，表明神经特异性脂质变化有助于PN的发病机制。许多已确定的脂质影响线粒体功能和线粒体生物能量学，这在离体腓肠神经和背根神经节感觉神经元中显著受损。总的来说，我们的数据表明，食用HFD会使神经脂质组和线粒体功能失调，这可能会导致糖尿病前期的PN。
As the prevalence of prediabetes and type 2 diabetes (T2D) continues to increase worldwide, accompanying complications are also on the rise. The most prevalent complication, peripheral neuropathy (PN), is a complex process which remains incompletely understood. Dyslipidemia is an emerging risk factor for PN in both prediabetes and T2D, suggesting that excess lipids damage peripheral nerves; however, the precise lipid changes that contribute to PN are unknown. To identify specific lipid changes associated with PN, we conducted an untargeted lipidomics analysis comparing the effect of high-fat diet (HFD) feeding on lipids in the plasma, liver, and peripheral nerve from three strains of mice (BL6, BTBR, and BKS). HFD feeding triggered distinct strain- and tissue-specific lipid changes, which correlated with PN in BL6 mice versus less robust murine models of metabolic dysfunction and PN (BTBR and BKS mice). The BL6 mice showed significant changes in neutral lipids, phospholipids, lysophospholipids, and plasmalogens within the nerve. Sphingomyelin (SM) and lysophosphatidylethanolamine (LPE) were two lipid species that were unique to HFD BL6 sciatic nerve compared to other strains (BTBR and BKS). Plasma and liver lipids were significantly altered in all murine strains fed a HFD independent of PN status, suggesting that nerve-specific lipid changes contribute to PN pathogenesis. Many of the identified lipids affect mitochondrial function and mitochondrial bioenergetics, which were significantly impaired in ex vivo sural nerve and dorsal root ganglion sensory neurons. Collectively, our data show that consuming a HFD dysregulates the nerve lipidome and mitochondrial function, which may contribute to PN in prediabetes.
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影响因子：
3.5
作者：
Basu Ball W;Neff JK;Gohil VM
通讯作者：
Gohil VM
影响因子：
4.5
作者：
Murray AJ;Knight NS;Little SE;Cochlin LE;Clements M;Clarke K
通讯作者：
Clarke K
DOI：
10.1016/j.biocel.2021.106135
发表时间：
2022-03
期刊：
The international journal of biochemistry & cell biology
影响因子：
--
作者：
Ampong I;John Ikwuobe O;Brown JEP;Bailey CJ;Gao D;Gutierrez-Merino J;Griffiths HR
通讯作者：
Griffiths HR
影响因子：
4
作者：
Aon MA;Bhatt N;Cortassa SC
通讯作者：
Cortassa SC
影响因子：
16.2
作者：
Callaghan BC;Feldman E;Liu J;Kerber K;Pop-Busui R;Moffet H;Karter AJ
通讯作者：
Karter AJ