Masoodi Mojgan, Kuda Ondrej, Rossmeisl Martin, Flachs Pavel, Kopecky Jan
Nestlé Institute of Health Sciences SA, EPFL Innovation Park, bâtiment H, 1015 Lausanne, Switzerland.
Department of Adipose Tissue Biology, Institute of Physiology Academy of Sciences of the Czech Republic, v.v.i., Prague, Czech Republic.
Biochim Biophys Acta. 2015 Apr;1851(4):503-18. doi: 10.1016/j.bbalip.2014.09.023. Epub 2014 Oct 12.
Obesity-associated low-grade inflammation of white adipose tissue (WAT) contributes to development of insulin resistance and other disorders. Accumulation of immune cells, especially macrophages, and macrophage polarization from M2 to M1 state, affect intrinsic WAT signaling, namely anti-inflammatory and proinflammatory cytokines, fatty acids (FA), and lipid mediators derived from both n-6 and n-3 long-chain PUFA such as (i) arachidonic acid (AA)-derived eicosanoids and endocannabinoids, and (ii) specialized pro-resolving lipid mediators including resolvins derived from both eicosapentaenoic (EPA) and docosahexaenoic acid (DHA), lipoxins (AA metabolites), protectins and maresins (DHA metabolites). In this respect, potential differences in modulating adipocyte metabolism by various lipid mediators formed by inflammatory M1 macrophages typical of obese state, and non-inflammatory M2 macrophages typical of lean state remain to be established. Studies in mice suggest that (i) transient accumulation of M2 macrophages could be essential for the control of tissue FA levels during activation of lipolysis, (ii) currently unidentified M2 macrophage-borne signaling molecule(s) could inhibit lipolysis and re-esterification of lipolyzed FA back to triacylglycerols (TAG/FA cycle), and (iii) the egress of M2 macrophages from rebuilt WAT and removal of the negative feedback regulation could allow for a full unmasking of metabolic activities of adipocytes. Thus, M2 macrophages could support remodeling of WAT to a tissue containing metabolically flexible adipocytes endowed with a high capacity of both TAG/FA cycling and oxidative phosphorylation. This situation could be exemplified by a combined intervention using mild calorie restriction and dietary supplementation with EPA/DHA, which enhances the formation of "healthy" adipocytes. This article is part of a Special Issue entitled Oxygenated metabolism of PUFA: analysis and biological relevance."
肥胖相关的白色脂肪组织（WAT）低度炎症会导致胰岛素抵抗和其他疾病的发生。免疫细胞尤其是巨噬细胞的积累，以及巨噬细胞从M2状态向M1状态的极化，会影响WAT的内在信号传导，即抗炎和促炎细胞因子、脂肪酸（FA）以及源自n-6和n-3长链多不饱和脂肪酸的脂质介质，例如：（i）花生四烯酸（AA）衍生的类二十烷酸和内源性大麻素，以及（ii）包括源自二十碳五烯酸（EPA）和二十二碳六烯酸（DHA）的消退素、脂氧素（AA代谢物）、保护素和maresins（DHA代谢物）在内的特殊促消退脂质介质。在这方面，由肥胖状态典型的炎性M1巨噬细胞和瘦状态典型的非炎性M2巨噬细胞形成的各种脂质介质在调节脂肪细胞代谢方面的潜在差异仍有待确定。对小鼠的研究表明：（i）M2巨噬细胞的短暂积累对于脂解激活过程中组织FA水平的控制可能至关重要；（ii）目前尚未确定的M2巨噬细胞携带的信号分子可能会抑制脂解以及将脂解产生的FA重新酯化为三酰甘油（TAG/FA循环）；（iii）M2巨噬细胞从重建的WAT中流出以及负反馈调节的消除可能会使脂肪细胞的代谢活动完全显现出来。因此，M2巨噬细胞可以支持WAT重塑为一种含有代谢灵活的脂肪细胞的组织，这些脂肪细胞具有高TAG/FA循环能力和氧化磷酸化能力。这种情况可以通过轻度热量限制和补充EPA/DHA的联合干预来举例说明，这种联合干预可增强“健康”脂肪细胞的形成。本文是名为“多不饱和脂肪酸的氧化代谢：分析与生物学意义”的特刊的一部分。
