Obesity Accelerates Age-Associated Defects in Human B Cells Through a Metabolic Reprogramming Induced by the Fatty Acid Palmitate.
Obesity Accelerates Age-Associated Defects in Human B Cells Through a Metabolic Reprogramming Induced by the Fatty Acid Palmitate.
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DOI：
10.3389/fragi.2021.828697
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发表时间：
2021
影响因子：
--
通讯作者：
Blomberg, Bonnie B.
中科院分区：
文献类型：
--
作者：
Frasca, Daniela;Romero, Maria;Garcia, Denisse;Diaz, Alain;Blomberg, Bonnie B.
我们检测了四组个体：青年瘦肉组(YL)、老年瘦肉组(EL)、青年肥胖组(YO)和老年肥胖组(EO)的血浆和血源性B细胞培养上清液中自身免疫抗体的分泌。我们发现Yo和El个体的分泌物是相似的，这表明肥胖会加速循环中B细胞的年龄相关缺陷。为了确定至少一个可能的分子途径，我们使用了一个体外模型，在该模型中，来自YL和EL个体的B细胞被脂肪酸棕榈酸酯(FA)刺激，FA是人体中最常见的饱和脂肪酸。使用棕榈酸酯的基本原理是，由于衰老和肥胖期间发生的自发脂解作用增加，循环中棕榈酸酯的水平会慢性增加，这可能会诱导自身免疫B细胞。结果表明，YL和EL患者的B细胞与FA棕榈酸酯体外孵育可诱导自身免疫抗体转录因子T-bet的mRNA表达和自身免疫抗体的分泌，YL患者的B细胞与EL患者的B细胞相似，证实了我们最初的假设。研究发现，在FA棕榈酸酯存在的情况下，自身免疫B细胞的产生与YL和EL个体的B细胞代谢重编程有关。这些结果表明了FA棕榈酸酯在诱导人类B细胞免疫衰老中的关键作用，并首次表明了代谢途径在这一过程中的重要性。
We have measured the secretion of autoimmune antibodies in plasma samples and in culture supernatants of blood-derived B cells from four groups of individuals: young lean (YL), elderly lean (EL), young obese (YO) and elderly obese (EO). We found secretion comparable in YO and EL individuals, suggesting that obesity accelerates age-associated defects in circulating B cells. To define at least one possible molecular pathway involved, we used an in vitro model in which B cells from YL and EL individuals have been stimulated with the Fatty Acid (FA) palmitate, the most common saturated FA in the human body. The rationale to use palmitate is that there is a chronic increase in circulating levels of palmitate, due to increased spontaneous lipolysis occurring during aging and obesity, and this may induce autoimmune B cells. Results herein show that in vitro incubation of B cells from YL and EL individuals with the FA palmitate induces mRNA expression of T-bet, the transcription factor for autoimmune antibodies, as well as secretion of autoimmune IgG antibodies, with B cells from YL individuals looking similar to B cells from EL individuals, confirming our initial hypothesis. The generation of autoimmune B cells in the presence of the FA palmitate was found to be associated with a metabolic reprogramming of B cells from both YL and EL individuals. These results altogether show the critical role of the FA palmitate in inducing human B cell immunosenescence and show for the first time the importance of metabolic pathways in this process.
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影响因子：
64.5
作者：
Cubillos-Ruiz JR;Silberman PC;Rutkowski MR;Chopra S;Perales-Puchalt A;Song M;Zhang S;Bettigole SE;Gupta D;Holcomb K;Ellenson LH;Caputo T;Lee AH;Conejo-Garcia JR;Glimcher LH
通讯作者：
Glimcher LH
影响因子：
12.6
作者：
Hass, DJ;Brensinger, CM;Lichtenstein, GR
通讯作者：
Lichtenstein, GR
影响因子：
37.8
作者：
Apovian CM;Gokce N
通讯作者：
Gokce N
影响因子：
7.3
作者：
Frasca D;Diaz A;Romero M;Blomberg BB
通讯作者：
Blomberg BB
影响因子：
5.6
作者：
Frasca D;Romero M;Diaz A;Garcia D;Thaller S;Blomberg BB
通讯作者：
Blomberg BB