High fat diet rapidly suppresses B lymphopoiesis by disrupting the supportive capacity of the bone marrow niche.
High fat diet rapidly suppresses B lymphopoiesis by disrupting the supportive capacity of the bone marrow niche.
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DOI：
10.1371/journal.pone.0090639
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发表时间：
2014
期刊：
影响因子：
3.7
通讯作者：
Rubin CT
中科院分区：
文献类型：
--
作者：
Adler BJ;Green DE;Pagnotti GM;Chan ME;Rubin CT
骨髓（BM）生态位是造血的主要部位，来自这个微环境的线索对维持造血至关重要。肥胖增加了终生对许多慢性疾病的易感性，并与白细胞生成缺陷有关。肥胖对造血组织施加的压力促使我们研究高脂肪饮食（HFD: 60%卡路里来自脂肪）对BM中B细胞发育的影响。7周龄雄性C57Bl/6J小鼠分别饲喂高脂（HFD）和常规饲料（RD），为期2天、1周和6周。与RD相比，HFD 2 d后b细胞群（B220+）未发生变化，1 w内b细胞比例下降了- 10%，6 w时下降了- 25% （p<0.05）。提取BM RNA，追踪b细胞发育标志物Il-7、Ebf-1和Pax-5的表达。在第2天，Il-7和Ebf-1的表达分别下降了- 20% （p = 0.08）和- 11% (p = 0.06)，而Pax-5的表达没有显著影响。然而，在1周时，与RD相比，HFD小鼠Il-7、Ebf-1和Pax-5的表达分别下降了-19%、- 20%和- 16%，到6周时，与RD相比，Il-7、Ebf-1和Pax-5的表达进一步降低至- 23%、- 29%和- 34% (p<0.05)，与此同时，骨髓间隙内脂肪侵入增加了+363% （p<0.01）。Il-7是早期b细胞谱系中的一个关键因子，由BM生态位中的支持细胞分泌，并且是b细胞承诺所必需的。这些数据表明，骨髓Il-7的表达以及b细胞的分化在HFD的作用下会迅速受损。在HFD仅2天后，Il-7表达被抑制的趋势表明，BM生态位和依赖于它的细胞对饮食是多么敏感，这最终可能导致代谢紊乱（如肥胖）的疾病易感性。
The bone marrow (BM) niche is the primary site of hematopoiesis, and cues from this microenvironment are critical to maintain hematopoiesis. Obesity increases lifetime susceptibility to a host of chronic diseases, and has been linked to defective leukogenesis. The pressures obesity exerts on hematopoietic tissues led us to study the effects of a high fat diet (HFD: 60% Kcal from fat) on B cell development in BM. Seven week old male C57Bl/6J mice were fed either a high fat (HFD) or regular chow (RD) diet for periods of 2 days, 1 week and 6 weeks. B-cell populations (B220+) were not altered after 2 d of HFD, within 1 w B-cell proportions were reduced by −10%, and by 6 w by −25% as compared to RD (p<0.05). BM RNA was extracted to track the expression of B-cell development markers Il-7, Ebf-1 and Pax-5. At 2 d, the expression of Il-7 and Ebf-1 were reduced by −20% (p = 0.08) and −11% (p = 0.06) whereas Pax-5 was not significantly impacted. At one week, however, the expressions of Il-7, Ebf-1, and Pax-5 in HFD mice fell by -19%, −20% and −16%, and by six weeks were further reduced to −23%, −29% and −34% as compared to RD (p<0.05 for all), a suppression paralleled by a +363% increase in adipose encroachment within the marrow space (p<0.01). Il-7 is a critical factor in the early B-cell lineage which is secreted by supportive cells in the BM niche, and is necessary for B-cell commitment. These data indicate that BM Il-7 expression, and by extension B-cell differentiation, are rapidly impaired by HFD. The trend towards suppressed expression of Il-7 following only 2 d of HFD demonstrates how susceptible the BM niche, and the cells which rely on it, are to diet, which ultimately could contribute to disease susceptibility in metabolic disorders such as obesity.
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