Ruth M R, Proctor S D, Field C J
Department of Agricultural Food and Nutritional Science, Alberta Institute for Human Nutrition, University of Alberta, Edmonton, Alberta, Canada.
Int J Obes (Lond). 2009 Jan;33(1):96-103. doi: 10.1038/ijo.2008.227. Epub 2008 Dec 2.
berrant immune responses have been identified in obesity; however, immune cells of lymph nodes residing in the inflammatory environment of visceral adipose tissue have been largely overlooked. Eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) can reduce inflammation and modify T-cell function and therefore may improve immune function in obesity. Thus, we determined the effects of feeding fish oil (FO) containing EPA and DHA on mesenteric lymph node (MLN) immune cell function.
In this study, 14-week-old obese, leptin receptor-deficient JCR:LA-cp rats (cp/cp) (n=10 per group) were randomized to one of three nutritionally adequate diets for 3 weeks: control (ctl, 0% EPA+DHA), low FO (LFO, 0.8% w/w EPA+DHA) or high FO (HFO, 1.4% w/w EPA+DHA). Lean JCR:LA-cp (Cp/cp or Cp/Cp) rats (n=5) were fed ctl diet. MLN cell phospholipid (PL) fatty acid composition, phenotypes and cytokine production were measured.
Obese ctl rats produced more IL-1beta, IL-4 and IL-10, despite a higher proportion of (n-3) polyunsaturated fatty acids (PUFAs) and a lower (n-6):(n-3) PUFA ratio in MLN PL compared with lean ctl rats (P<0.05). Concanavalin A-stimulated IL-2 production did not differ from lean rats even though obese ctl rats had a lower proportion of CD4(+)CD25(+) cells (P<0.05). Feeding FO to obese rats increased the incorporation of (n-3) PUFA into MLN PL and normalized production of IL-1beta (HFO only), IL-4 and IL-10 to the levels similar to lean ctl rats (P<0.05).
We demonstrate for the first time that obese JCR:LA-cp rats have impaired responses of MLN immune cells to mitogen stimulation and altered PL fatty acid composition. Feeding FO lowered the ex vivo inflammatory response (HFO only) and production of Th2 cytokines, without changing IL-2 production from ConA-stimulated splenocytes, which may occur independent of leptin signalling.
已在肥胖症中发现异常免疫反应;然而,位于内脏脂肪组织炎症环境中的淋巴结免疫细胞在很大程度上被忽视了。二十碳五烯酸(EPA)和二十二碳六烯酸(DHA)可减轻炎症并改变T细胞功能,因此可能改善肥胖症中的免疫功能。因此,我们确定了喂食含EPA和DHA的鱼油(FO)对肠系膜淋巴结(MLN)免疫细胞功能的影响。
在本研究中,将14周龄的肥胖、瘦素受体缺陷型JCR:LA-cp大鼠(cp/cp)(每组n = 10)随机分为三种营养充足的饮食组之一,持续3周:对照组(ctl,0% EPA + DHA)、低鱼油组(LFO,0.8% w/w EPA + DHA)或高鱼油组(HFO,1.4% w/w EPA + DHA)。将瘦的JCR:LA-cp(Cp/cp或Cp/Cp)大鼠(n = 5)喂食ctl饮食。测量MLN细胞磷脂(PL)脂肪酸组成、表型和细胞因子产生情况。
尽管与瘦的ctl大鼠相比,肥胖的ctl大鼠MLN PL中(n - 3)多不饱和脂肪酸(PUFA)比例更高且(n - 6):(n - 3)PUFA比值更低,但肥胖的ctl大鼠产生更多的IL - 1β、IL - 4和IL - 10(P < 0.05)。即使肥胖的ctl大鼠CD4(+)CD25(+)细胞比例较低(P < 0.05),伴刀豆球蛋白A刺激的IL - 2产生与瘦大鼠并无差异。给肥胖大鼠喂食FO可增加(n - 3)PUFA掺入MLN PL,并使IL - 1β(仅HFO组)、IL - 4和IL - 10的产生恢复正常,达到与瘦的ctl大鼠相似的水平(P < 0.05)。
我们首次证明肥胖的JCR:LA-cp大鼠MLN免疫细胞对丝裂原刺激的反应受损,且PL脂肪酸组成发生改变。喂食FO可降低体外炎症反应(仅HFO组)和Th2细胞因子的产生,而不改变伴刀豆球蛋白A刺激的脾细胞产生的IL - 2,这可能独立于瘦素信号传导而发生。