背景:棕色脂肪组织(BAT)燃烧脂质和葡萄糖以产生热量。通过这个非颤抖的产热过程,BAT在寒冷环境中的体温调节中起着关键作用,但其对免疫引起的发热的作用尚不清楚。
方法:男性APOE*3-莱顿。CETP小鼠,一个完善的人样脂蛋白代谢模型,和野生型小鼠腹膜内注射肠沙门氏菌(S.tm)。能量消耗和衬底利用率,血浆脂质水平,脂肪组织摄取脂肪酸,并检查了脂肪组织中的脂质含量和产热标志物。
结果:S.tm感染导致一系列特征性症状,包括体温升高和体重下降。感染后72小时,全身能量消耗显着降低,但是脂肪氧化增加,并伴有血浆甘油三酯(TG)水平的大幅降低,如APOE*3-Leiden所示。CETP小鼠。S.tm感染强烈增加了BAT对富含TG的脂蛋白(TRLs)中脂肪酸的摄取,与感染小鼠的体温呈正相关。对野生型或APOE*3-莱顿的BAT进行组织学检查。CETP小鼠,观察到酪氨酸羟化酶水平升高,指示受刺激的交感神经活动。此外,基因表达谱与更多的肾上腺素能刺激一致,而脂质含量降低。此外,观察到白色脂肪组织褐变,由TG衍生的脂肪酸摄取适度增加证明,多房细胞的存在,和诱导UCP-1表达。
结论:我们建议BAT,或一般的产热脂肪组织,涉及在侵入性细菌感染后维持升高的体温。
BACKGROUND: Brown adipose tissue (BAT) combusts lipids and glucose to generate heat. Via this process of non-shivering thermogenesis, BAT plays a pivotal role in thermoregulation in cold environments, but its contribution to immune-induced fever is less clear.
METHODS: Male APOE*3-Leiden.CETP mice, a well-established model for human-like lipoprotein metabolism, and wildtype mice were given an intraperitoneal injection of Salmonella enterica serovar Typhimurium (S.tm). Energy expenditure and substrate utilization, plasma lipid levels, fatty acid uptake by adipose tissues, and lipid content and thermogenic markers in adipose tissues were examined.
RESULTS: S.tm infection led to a set of characteristic symptoms, including elevated body temperature and decreased body weight. Whole-body energy expenditure was significantly decreased 72 hours post-infection, but fat oxidation was increased and accompanied by a substantial reduction in plasma triglyceride (TG) levels as demonstrated in APOE*3-Leiden.CETP mice. S.tm infection strongly increased uptake of fatty acids from TG-rich lipoproteins (TRLs) by BAT, which showed a positive correlation with body temperature in infected mice. Upon histological examination of BAT from wildtype or APOE*3-Leiden.CETP mice, elevated levels of tyrosine hydroxylase were observed, indicative of stimulated sympathetic activity. In addition, the gene expression profile was consistent with more adrenergic stimulation, while lipid content was reduced. Furthermore, browning of white adipose tissue was observed, evidenced by a modest increase in TG-derived fatty acid uptake, the presence of multilocular cells, and induction of UCP-1 expression.
CONCLUSIONS: We proposed that BAT, or thermogenic adipose tissue in general, is involved in the maintenance of elevated body temperature upon invasive bacterial infection.