Vámos Attila, Shaw Abhirup, Varga Klára, Csomós István, Mocsár Gábor, Balajthy Zoltán, Lányi Cecília, Bacso Zsolt, Szatmári-Tóth Mária, Kristóf Endre
Laboratory of Cell Biochemistry, Department of Biochemistry and Molecular Biology, Faculty of Medicine, University of Debrecen, H-4032 Debrecen, Hungary.
Doctoral School of Molecular Cell and Immune Biology, University of Debrecen, H-4032 Debrecen, Hungary.
Pharmaceuticals (Basel). 2022 Mar 17;15(3):363. doi: 10.3390/ph15030363.
Brown and beige adipocytes have multilocular lipid droplets, express uncoupling protein (UCP) 1, and promote energy expenditure. In rodents, when the stimulus of browning subsides, parkin-dependent mitophagy is activated and dormant beige adipocytes persist. In humans, however, the molecular events during the beige to white transition have not been studied in detail. In this study, human primary subcutaneous abdominal preadipocytes were differentiated to beige for 14 days, then either the beige culture conditions were applied for an additional 14 days or it was replaced by a white medium. Control white adipocytes were differentiated by their specific cocktail for 28 days. Peroxisome proliferator-activated receptor γ-driven beige differentiation resulted in increased mitochondrial biogenesis, UCP1 expression, fragmentation, and respiration as compared to white. Morphology, UCP1 content, mitochondrial fragmentation, and basal respiration of the adipocytes that underwent transition, along with the induction of mitophagy, were similar to control white adipocytes. However, white converted beige adipocytes had a stronger responsiveness to dibutyril-cAMP, which mimics adrenergic stimulus, than the control white ones. Gene expression patterns showed that the removal of mitochondria in transitioning adipocytes may involve both parkin-dependent and -independent pathways. Preventing the entry of beige adipocytes into white transition can be a feasible way to maintain elevated thermogenesis and energy expenditure.
棕色和米色脂肪细胞具有多泡脂滴，表达解偶联蛋白（UCP）1，并促进能量消耗。在啮齿动物中，当褐变刺激消退时，帕金蛋白依赖性线粒体自噬被激活，休眠的米色脂肪细胞持续存在。然而，在人类中，米色向白色转变过程中的分子事件尚未得到详细研究。在本研究中，将人原发性腹部皮下前脂肪细胞分化为米色14天，然后要么将米色培养条件再维持14天，要么换成白色培养基。对照白色脂肪细胞通过其特定的混合试剂分化28天。与白色脂肪细胞相比，过氧化物酶体增殖物激活受体γ驱动的米色分化导致线粒体生物发生增加、UCP1表达增加、线粒体碎片化增加以及呼吸作用增强。经历转变的脂肪细胞的形态、UCP1含量、线粒体碎片化和基础呼吸，以及线粒体自噬的诱导，与对照白色脂肪细胞相似。然而，白色转米色的脂肪细胞对模拟肾上腺素能刺激的二丁酰环磷腺苷（dibutyril-cAMP）的反应比对照白色脂肪细胞更强。基因表达模式表明，转变中的脂肪细胞中线粒体的清除可能涉及帕金蛋白依赖性和非依赖性途径。防止米色脂肪细胞进入白色转变可能是维持产热和能量消耗升高的一种可行方法。
