小柯机器人

德国亥姆霍兹慕尼黑中心Stephan Herzig等研究人员合作发现，巨噬细胞-肝细胞糖皮质激素受体轴协调空腹酮生成。该项研究成果于2022年2月3日在线发表在《细胞—代谢》杂志上。

研究人员结合了细胞类型解析基因组学和计算方法来绘制空腹期间肝细胞和肝脏巨噬细胞之间的交流图谱。研究人员确定糖皮质激素受体（GR）是禁食诱导的巨噬细胞分泌组（包括禁食抑制的细胞因子）重新编程的关键驱动因素，并显示缺乏巨噬细胞GR会损害禁食期间的生酮作用，以及内毒素血症。从机制上讲，巨噬细胞GR抑制了肿瘤坏死因子（TNF）的表达，并促进了肝细胞GR的核转位，从而激活脂肪氧化/生酮相关的基因程序，该程序由GR和肝细胞中的过氧化物酶体增殖激活受体α（PPARα）合作诱导。

总之，这项研究结果证明了常驻肝脏的巨噬细胞如何直接影响肝细胞的生酮作用，从而也概述了免疫系统在炎症性疾病和感染期间可以设定代谢基调的策略。

据悉，空腹代谢和免疫是紧密相连的；然而，在健康受试者空腹期间，免疫细胞是如何促进代谢平衡的，这一点在很大程度上是未知的。

附：英文原文

Title: A macrophage-hepatocyte glucocorticoid receptor axis coordinates fasting ketogenesis

Author: Anne Loft, Sren Fisker Schmidt, Giorgio Caratti, Ulrich Stifel, Jesper Havelund, Revathi Sekar, Yun Kwon, Alba Sulaj, Kan Kau Chow, Ana Jimena Alfaro, Thomas Schwarzmayr, Nikolaj Rittig, Mads Svart, Foivos-Filippos Tsokanos, Adriano Maida, Andreas Blutke, Annette Feuchtinger, Niels Mller, Matthias Blüher, Peter Nawroth, Julia Szendrdi, Nils J. Frgeman, Anja Zeigerer, Jan Tuckermann, Stephan Herzig

Issue&Volume: 2022-02-03

Abstract: Fasting metabolism and immunity are tightly linked; however, it is largely unknownhow immune cells contribute to metabolic homeostasis during fasting in healthy subjects.Here, we combined cell-type-resolved genomics and computational approaches to mapcrosstalk between hepatocytes and liver macrophages during fasting. We identifiedthe glucocorticoid receptor (GR) as a key driver of fasting-induced reprogrammingof the macrophage secretome including fasting-suppressed cytokines and showed thatlack of macrophage GR impaired induction of ketogenesis during fasting as well asendotoxemia. Mechanistically, macrophage GR suppressed the expression of tumor necrosisfactor (TNF) and promoted nuclear translocation of hepatocyte GR to activate a fatoxidation/ketogenesis-related gene program, cooperatively induced by GR and peroxisomeproliferator-activated receptor alpha (PPARα) in hepatocytes. Together, our resultsdemonstrate how resident liver macrophages directly influence ketogenesis in hepatocytes,thereby also outlining a strategy by which the immune system can set the metabolictone during inflammatory disease and infection.

DOI: 10.1016/j.cmet.2022.01.004

Source: https://www.cell.com/cell-metabolism/fulltext/S1550-4131(22)00004-3

Cell Metabolism：《细胞—代谢》，创刊于2005年。隶属于细胞出版社，最新IF：31.373
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