Palafox-Sánchez Victoria, Ying Zhe, Royes Luiz Fernando Freire, Gomez-Pinilla Fernando
Department of Integrative Biology & Physiology, UCLA, Los Angeles, USA.
Department of Integrative Biology & Physiology, UCLA, Los Angeles, USA; Exercise Biochemistry Laboratory, Center of Physical Education and Sports, Federal University of Santa Maria - UFSM, Santa Maria, RS, Brazil.
Biochim Biophys Acta Mol Basis Dis. 2021 Apr 1;1867(4):166078. doi: 10.1016/j.bbadis.2021.166078. Epub 2021 Jan 12.
To shed light on the impact of systemic physiology on the pathology of traumatic brain injury (TBI), we examine the effects of TBI (concussive injury) and dietary fructose on critical aspects of lipid homeostasis in the brain and liver of young-adult rats. Lipids are integral components of brain structure and function, and the liver has a role on the synthesis and metabolism of lipids. Fructose is mainly metabolized in the liver with potential implications for brain function. Lipidomic analysis accompanied by unbiased sparse partial least squares discriminant analysis (sPLS-DA) identified lysophosphatidylcholine (LPC) and cholesterol ester (CE) as the top lipid families impacted by TBI and fructose in the hippocampus, and only LPC (16:0) was associated with hippocampal-dependent memory performance. Fructose and TBI elevated liver pro-inflammatory markers, interleukin-1α (IL-1α), Interferon-γ (IFN-γ) that correlated with hippocampal-dependent memory dysfunction, and monocyte chemoattractant protein-1 (MCP-1) positively correlated with LPC levels in the hippocampus. The effects of fructose were more pronounced in the liver, in agreement with the role of liver on fructose metabolism and suggest that fructose could exacerbate liver inflammation caused by TBI. The overall results indicate that TBI and fructose interact to influence systemic and central inflammation by engaging liver lipids. The impact of TBI and fructose diet on the periphery provides a therapeutic target to counteract the TBI pathogenesis.
为了阐明全身生理对创伤性脑损伤（TBI）病理的影响，我们研究了TBI（脑震荡损伤）和膳食果糖对年轻成年大鼠脑和肝脏脂质稳态关键方面的影响。脂质是脑结构和功能的重要组成部分，肝脏在脂质的合成和代谢中发挥作用。果糖主要在肝脏中代谢，可能对脑功能产生影响。脂质组学分析结合无偏稀疏偏最小二乘判别分析（sPLS-DA）确定溶血磷脂酰胆碱（LPC）和胆固醇酯（CE）是海马体中受TBI和果糖影响最大的脂质家族，并且只有LPC（16:0）与海马体依赖性记忆表现相关。果糖和TBI升高了肝脏促炎标志物白细胞介素-1α（IL-1α）、与海马体依赖性记忆功能障碍相关的干扰素-γ（IFN-γ），以及与海马体中LPC水平呈正相关的单核细胞趋化蛋白-1（MCP-1）。果糖的影响在肝脏中更为明显，这与肝脏在果糖代谢中的作用一致，表明果糖可能会加剧TBI引起的肝脏炎症。总体结果表明，TBI和果糖相互作用，通过影响肝脏脂质来影响全身和中枢炎症。TBI和果糖饮食对周围组织的影响为对抗TBI发病机制提供了一个治疗靶点。
