Microglial Lipid Biology in the Hypothalamic Regulation of Metabolic Homeostasis.
Microglial Lipid Biology in the Hypothalamic Regulation of Metabolic Homeostasis.
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DOI：
10.3389/fendo.2021.668396
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发表时间：
2021
影响因子：
5.2
通讯作者：
Valdearcos M
中科院分区：
文献类型：
--
作者：
Folick A;Koliwad SK;Valdearcos M
在哺乳动物中，骨髓细胞有助于维持外周代谢组织的稳态，并且它们的免疫失调有助于肥胖和相关代谢疾病的进展。越来越多的证据表明，先天性免疫细胞也作为功能调节器内的中基底下丘脑（MBH），一个关键的大脑区域控制能量和葡萄糖稳态。具体而言，小胶质细胞，CNS的驻留实质髓样细胞，在脑生理学和病理学中发挥重要作用。最近的研究揭示了一系列不断扩大的小胶质细胞功能，超出了它们作为免疫哨兵的既定角色，包括在大脑发育，电路完善和突触组织中的作用。我们发现小胶质细胞通过传递过量营养消耗引起的信息来调节MBH功能。例如，小胶质细胞可以感觉到饱和脂肪的过度消耗，并相应地指示MBH内的神经元，从而导致能量平衡的响应性改变。有趣的是，最近出现的高分辨率单细胞技术使特定的小胶质细胞群体和表型能够以前所未有的细节进行分析。这些技术突出了小胶质细胞的特定亚群，这些亚群以其调节脂质代谢基因表达的能力而闻名，所述脂质代谢基因包括脂蛋白脂肪酶（LPL）、载脂蛋白E（APOE）和髓样细胞上表达的触发受体2（TREM2）。这种转录特征的发现突出了小胶质细胞脂质代谢作为脑健康和疾病发病机制的决定因素，对脑疾病和潜在代谢疾病的治疗具有有趣的意义。在这里，我们回顾了我们目前的理解如何在小胶质细胞脂质代谢的变化可能会影响下丘脑控制全身代谢。
In mammals, myeloid cells help maintain the homeostasis of peripheral metabolic tissues, and their immunologic dysregulation contributes to the progression of obesity and associated metabolic disease. There is accumulating evidence that innate immune cells also serve as functional regulators within the mediobasal hypothalamus (MBH), a critical brain region controlling both energy and glucose homeostasis. Specifically, microglia, the resident parenchymal myeloid cells of the CNS, play important roles in brain physiology and pathology. Recent studies have revealed an expanding array of microglial functions beyond their established roles as immune sentinels, including roles in brain development, circuit refinement, and synaptic organization. We showed that microglia modulate MBH function by transmitting information resulting from excess nutrient consumption. For instance, microglia can sense the excessive consumption of saturated fats and instruct neurons within the MBH accordingly, leading to responsive alterations in energy balance. Interestingly, the recent emergence of high-resolution single-cell techniques has enabled specific microglial populations and phenotypes to be profiled in unprecedented detail. Such techniques have highlighted specific subsets of microglia notable for their capacity to regulate the expression of lipid metabolic genes, including lipoprotein lipase (LPL), apolipoprotein E (APOE) and Triggering Receptor Expressed on Myeloid Cells 2 (TREM2). The discovery of this transcriptional signature highlights microglial lipid metabolism as a determinant of brain health and disease pathogenesis, with intriguing implications for the treatment of brain disorders and potentially metabolic disease. Here we review our current understanding of how changes in microglial lipid metabolism could influence the hypothalamic control of systemic metabolism.
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DOI：
10.1038/ijo.2017.231
发表时间：
2018-03
期刊：
International journal of obesity (2005)
影响因子：
--
作者：
Banks WA;Farr SA;Salameh TS;Niehoff ML;Rhea EM;Morley JE;Hanson AJ;Hansen KM;Craft S
通讯作者：
Craft S
对人类、黑猩猩、猕猴和小鼠组织的大规模分析揭示了脑脂质组的组织和进化
影响因子：
16.2
作者：
Bozek, Katarzyna;Wei, Yuning;Khaitovich, Philipp
通讯作者：
Khaitovich, Philipp
影响因子：
4.7
作者：
Bouyakdan, Khalil;Taib, Bouchra;Alquier, Thierry
通讯作者：
Alquier, Thierry
影响因子：
7.7
作者：
Beutler, Lisa R.;Corpuz, Timothy, V;Knight, Zachary A.
通讯作者：
Knight, Zachary A.
影响因子：
11
作者：
Cansell, C.;Castel, J.;Luquet, S.
通讯作者：
Luquet, S.