A BAFF/APRIL axis regulates obesogenic diet-driven weight gain.
A BAFF/APRIL axis regulates obesogenic diet-driven weight gain.
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DOI：
10.1038/s41467-021-23084-1
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发表时间：
2021-05-18
影响因子：
16.6
通讯作者：
Divanovic S
中科院分区：
文献类型：
--
作者：
Chan CC;Harley ITW;Pfluger PT;Trompette A;Stankiewicz TE;Allen JL;Moreno-Fernandez ME;Damen MSMA;Oates JR;Alarcon PC;Doll JR;Flick MJ;Flick LM;Sanchez-Gurmaches J;Mukherjee R;Karns R;Helmrath M;Inge TH;Weisberg SP;Pamp SJ;Relman DA;Seeley RJ;Tschöp MH;Karp CL;Divanovic S
免疫介质对体重稳态的影响仍然不明确。在缺乏Toll样受体信号负调节因子的小鼠中，对饮食诱导的肥胖的抵抗性的研究偶然发现了B细胞活化因子（BAFF）的作用。在这里，我们表明，在多个小鼠模型中，BAFF的过度表达与体重增加的保护有关，近似于BAFF浓度的对数线性剂量反应关系。BAFF刺激的皮下白色脂肪细胞的基因表达分析揭示了脂质代谢途径的上调，BAFF诱导白色脂肪组织（WAT）脂解。来自BAFF过表达小鼠的棕色脂肪组织（BAT）表现出Ucp 1表达增加，BAFF促进棕色脂肪细胞呼吸和体内能量消耗。增殖诱导配体（APRIL），BAFF同源物，类似地调节WAT和BAT脂质处理。BAFF和APRIL的基因缺失增加了饮食诱导的肥胖。最后，BAFF/APRIL效应在人脂肪细胞中是保守的，并且较高的BAFF/APRIL水平与减肥手术后较大的BMI降低相关。总之，BAFF/APRIL轴是体重增加和脂肪组织功能的多方面免疫调节剂。免疫系统和脂肪组织之间的相互作用有助于体重的调节，然而，其潜在机制仍不完全清楚。在这里，作者剖析了两种结构和功能相似的免疫介质BAFF和APRIL在调节饮食诱导的体重增加和脂肪细胞脂质处理中的作用。
The impact of immune mediators on weight homeostasis remains underdefined. Interrogation of resistance to diet-induced obesity in mice lacking a negative regulator of Toll-like receptor signaling serendipitously uncovered a role for B cell activating factor (BAFF). Here we show that overexpression of BAFF in multiple mouse models associates with protection from weight gain, approximating a log-linear dose response relation to BAFF concentrations. Gene expression analysis of BAFF-stimulated subcutaneous white adipocytes unveils upregulation of lipid metabolism pathways, with BAFF inducing white adipose tissue (WAT) lipolysis. Brown adipose tissue (BAT) from BAFF-overexpressing mice exhibits increased Ucp1 expression and BAFF promotes brown adipocyte respiration and in vivo energy expenditure. A proliferation-inducing ligand (APRIL), a BAFF homolog, similarly modulates WAT and BAT lipid handling. Genetic deletion of both BAFF and APRIL augments diet-induced obesity. Lastly, BAFF/APRIL effects are conserved in human adipocytes and higher BAFF/APRIL levels correlate with greater BMI decrease after bariatric surgery. Together, the BAFF/APRIL axis is a multifaceted immune regulator of weight gain and adipose tissue function. Interactions between the immune system and adipose tissue contribute to the regulation of body weight, however, the underlying mechanisms remain incompletely understood. Here the authors dissect the role of two structurally and functionally similar immune mediators, BAFF and APRIL, in modifying diet-induced weight gain and adipocyte lipid handling.
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影响因子：
120.7
作者：
Flegal, Katherine M.;Carroll, Margaret D.;Curtin, Lester R.
通讯作者：
Curtin, Lester R.
影响因子：
7.7
作者：
Cani, Patrice D.;Amar, Jacques;Burcelin, Remy
通讯作者：
Burcelin, Remy
影响因子：
82.9
作者：
Fischer K;Ruiz HH;Jhun K;Finan B;Oberlin DJ;van der Heide V;Kalinovich AV;Petrovic N;Wolf Y;Clemmensen C;Shin AC;Divanovic S;Brombacher F;Glasmacher E;Keipert S;Jastroch M;Nagler J;Schramm KW;Medrikova D;Collden G;Woods SC;Herzig S;Homann D;Jung S;Nedergaard J;Cannon B;Tschöp MH;Müller TD;Buettner C
通讯作者：
Buettner C
影响因子：
29
作者：
Eguchi, Jun;Yan, Qing-Wu;Rosen, Evan D.
通讯作者：
Rosen, Evan D.
DOI：
10.1073/pnas.1215840110
发表时间：
2013-03-26
影响因子：
11.1
作者：
DeFuria, Jason;Belkina, Anna C.;Nikolajczyk, Barbara S.
通讯作者：
Nikolajczyk, Barbara S.