棕色脂肪细胞产热的完全激活需要 Basigin 作用,The FEBS Journal

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棕色脂肪细胞产热的完全激活需要 Basigin 作用
The FEBS Journal ( IF 5.5 ) Pub Date : 2023-01-03 , DOI: 10.1111/febs.16716
Kaja Rupar ₁ , Marie S Isidor ₁ , Lidia Argemi-Muntadas ₁ , Marina Agueda-Oyarzabal ₁ , Kaja Plucińska ₁ , Erin L Brown ₁ , Matthias Mattanovich _{1,

2} , Simone Bossi ₁ , Marco Tozzi ₁ , David Tandio ₁ , Patricia S S Petersen ₁ , Tora I Henriksen ₃ , Kajetan Trošt ₁ , Jacob B Hansen ₄ , Zachary Gerhart-Hines ₁ , Søren Nielsen ₃ , Thomas Moritz ₁ , Brice Emanuelli ₁

Affiliation

探索负责棕色脂肪组织 (BAT) 高代谢活动的机制对于利用其能量耗散能力进行治疗至关重要。Basigin (Bsg) 是一种多功能的高度糖基化跨膜蛋白，最近被提议作为区分“白色”和“棕色”脂肪细胞的 98 个关键标记之一，但其在产热棕色脂肪细胞中的功能尚不清楚。在这里，我们报告Bsg与小鼠肥胖呈负相关。相比之下，Bsg表达在 BAT 的成熟脂肪细胞部分中在冷适应后增加。此外，Bsg 水平在棕色脂肪细胞体外成熟过程中被高度诱导并且以 HIF-1α 依赖性方式在 β-肾上腺素能刺激下进一步增加。siRNA 介导的Bsg基因在培养的棕色脂肪细胞中的沉默不影响脂肪生成和线粒体功能。然而，线粒体呼吸、脂肪分解和Ucp1显着降低当被去甲肾上腺素激活时，在缺乏 Bsg 的脂肪细胞中观察到转录。此外，使用气相色谱/质谱-飞行时间分析来评估细胞代谢物的组成，我们证明缺乏 Bsg 的棕色脂肪细胞具有较低水平的细胞内乳酸和乙酰乙酸。Bsg 还需要调节 NE 刺激的脂肪细胞中的细胞内 AcAc 和三羧酸循环中间水平。我们的研究强调了 Bsg 在活跃的棕色脂肪细胞中的关键作用，可能是通过控制细胞代谢来实现的。

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Full activation of thermogenesis in brown adipocytes requires Basigin action

Exploring mechanisms responsible for brown adipose tissue's (BAT) high metabolic activity is crucial to exploit its energy-dissipating ability for therapeutic purposes. Basigin (Bsg), a multifunctional highly glycosylated transmembrane protein, was recently proposed as one of the 98 critical markers allowing to distinguish ‘white’ and ‘brown’ adipocytes, yet its function in thermogenic brown adipocytes is unknown. Here, we report that Bsg is negatively associated with obesity in mice. By contrast, Bsg expression increased in the mature adipocyte fraction of BAT upon cold acclimation. Additionally, Bsg levels were highly induced during brown adipocyte maturation in vitro and were further increased upon β-adrenergic stimulation in a HIF-1α-dependent manner. siRNA-mediated Bsg gene silencing in cultured brown adipocytes did not impact adipogenesis nor mitochondrial function. However, a significant decrease in mitochondrial respiration, lipolysis and Ucp1 transcription was observed in adipocytes lacking Bsg, when activated by norepinephrine. Furthermore, using gas chromatography/mass spectrometry–time-of-flight analysis to assess the composition of cellular metabolites, we demonstrate that brown adipocytes lacking Bsg have lower levels of intracellular lactate and acetoacetate. Bsg was additionally required to regulate intracellular AcAc and tricarboxylic acid cycle intermediate levels in NE-stimulated adipocytes. Our study highlights the critical role of Bsg in active brown adipocytes, possibly by controlling cellular metabolism.

更新日期：2023-01-03

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