Fatty Acid Metabolite Profiling Reveals Oxylipins as Markers of Brown but Not Brite Adipose Tissue

Fatty Acid Metabolite Profiling Reveals Oxylipins as Markers of Brown but Not Brite Adipose Tissue
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DOI:
10.3389/fendo.2020.00073
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发表时间:
2020-02-21
影响因子:
5.2
通讯作者:
Klingenspor, Martin
Klingenspor, Martin
中科院分区:
医学2区
文献类型:
--
作者:
Dieckmann, Sebastian;Maurer, Stefanie;Klingenspor, Martin

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ω-6和ω-3多不饱和脂肪酸的代谢产物是参与脂肪生成和能量平衡调节的重要信号分子。这些代谢物中的一些属于氧化脂质类,与棕色或棕色脂肪组织介导的小鼠非颤抖性产热有关。我们的目的是确定新的分子与产热潜力,并澄清这些发现的相关性,在翻译的背景下。因此,我们表征并比较了具有不同丰度的棕色或棕色脂肪细胞的鼠和人脂肪组织的氧脂素谱。在适应不同环境温度的C57 BL/6 J小鼠的棕色和白色脂肪组织中以及在人锁骨上棕色和白色脂肪组织的活组织检查中,对一组广泛的36种脂肪酸代谢物进行了定量。小鼠棕色脂肪组织的氧脂素谱与白色脂肪组织没有区别,表明体内脂肪组织布朗宁与氧脂素代谢的主要变化无关。人棕色和白色脂肪组织也显示出相似的代谢产物谱。这与先前的研究一致,该研究提出人棕色脂肪组织类似于代表棕色和白色脂肪细胞的异质混合物的鼠棕色脂肪组织的性质。尽管总体氧脂素谱用作真正棕色而非白色脂肪组织中产热脂肪细胞丰度的标志物,但我们鉴定了5-HETE和5,6-EET作为与人BAT和鼠棕色脂肪中棕色或棕色脂肪细胞丰度一致相关的单独化合物。进一步的研究需要确定这些候选人是否仅仅是生热能力的标志物或功能效应物。
Metabolites of omega-6 and omega-3 polyunsaturated fatty acids are important signaling molecules implicated in the control of adipogenesis and energy balance regulation. Some of these metabolites belonging to the group of oxylipins have been associated with non-shivering thermogenesis in mice mediated by brown or brite adipose tissue. We aimed to identify novel molecules with thermogenic potential and to clarify the relevance of these findings in a translational context. Therefore, we characterized and compared the oxylipin profiles of murine and human adipose tissues with different abundance of brown or brite adipocytes. A broad panel of 36 fatty acid metabolites was quantified in brown and white adipose tissues of C57BL/6J mice acclimatized to different ambient temperatures and in biopsies of human supraclavicular brown and white adipose tissue. The oxylipin profile of murine brite adipose tissue was not distinguishable from white adipose tissue, suggesting that adipose tissue browning in vivo is not associated with major changes in the oxylipin metabolism. Human brown and white adipose tissue also exhibited similar metabolite profiles. This is in line with previous studies proposing human brown adipose tissue to resemble the nature of murine brite adipose tissue representing a heterogeneous mixture of brite and white adipocytes. Although the global oxylipin profile served as a marker for the abundance of thermogenic adipocytes in bona fide brown but not white adipose tissue, we identified 5-HETE and 5,6-EET as individual compounds consistently associated with the abundance of brown or brite adipocytes in human BAT and murine brite fat. Further studies need to establish whether these candidates are mere markers or functional effectors of thermogenic capacity.