Liu Ying-Hua, Li Xiang-Yong, Chen Chih-Yu, Zhang Hong-Man, Kang Jing X
Laboratory for Lipid Medicine and Technology (LLMT), Massachusetts General Hospital and Harvard Medical School, Boston, MA 02129, USA.
Nutrition Department, People's Liberation Army General Hospital, Beijing 100853, China.
Mar Drugs. 2015 Feb 13;13(2):1026-36. doi: 10.3390/md13021026.
Bacterial endotoxin lipopolysaccharide (LPS)-induced sepsis is a critical medical condition, characterized by a severe systemic inflammation and rapid loss of muscle mass. Preventive and therapeutic strategies for this complex disease are still lacking. Here, we evaluated the effect of omega-3 (n-3) polyunsaturated fatty acid (PUFA) intervention on LPS-challenged mice with respect to inflammation, body weight and the expression of Toll-like receptor 4 (TLR4) pathway components. LPS administration induced a dramatic loss of body weight within two days. Treatment with n-3 PUFA not only stopped loss of body weight but also gradually reversed it back to baseline levels within one week. Accordingly, the animals treated with n-3 PUFA exhibited markedly lower levels of inflammatory cytokines or markers in plasma and tissues, as well as down-regulation of TLR4 pathway components compared to animals without n-3 PUFA treatment or those treated with omega-6 PUFA. Our data demonstrate that n-3 PUFA intervention can suppress LPS-induced inflammation and weight loss via, at least in part, down-regulation of pro-inflammatory targets of the TLR4 signaling pathway, and highlight the therapeutic potential of n-3 PUFA in the management of sepsis.
细菌内毒素脂多糖（LPS）诱导的脓毒症是一种危急的医学病症，其特征为严重的全身炎症反应和肌肉质量迅速丧失。针对这种复杂疾病的预防和治疗策略仍然匮乏。在此，我们评估了ω-3（n-3）多不饱和脂肪酸（PUFA）干预对LPS攻击小鼠在炎症、体重以及Toll样受体4（TLR4）信号通路组分表达方面的影响。给予LPS在两天内导致体重显著下降。用n-3 PUFA治疗不仅阻止了体重下降，而且在一周内逐渐使其恢复至基线水平。相应地，与未用n-3 PUFA治疗的动物或用ω-6 PUFA治疗的动物相比，用n-3 PUFA治疗的动物血浆和组织中的炎性细胞因子或标志物水平显著降低，同时TLR4信号通路组分下调。我们的数据表明，n-3 PUFA干预可至少部分地通过下调TLR4信号通路的促炎靶点来抑制LPS诱导的炎症和体重减轻，并突出了n-3 PUFA在脓毒症治疗中的潜在应用价值。
