Department of Pathology and Immunology, Washington University School of Medicine, St Louis, MO 63110, USA.
Department of Pathology and Immunology, Washington University School of Medicine, St Louis, MO 63110, USA.
Cell Metab. 2022 Oct 4;34(10):1499-1513.e8. doi: 10.1016/j.cmet.2022.08.010. Epub 2022 Sep 6.
Adipocytes transfer mitochondria to macrophages in white and brown adipose tissues to maintain metabolic homeostasis. In obesity, adipocyte-to-macrophage mitochondria transfer is impaired, and instead, adipocytes release mitochondria into the blood to induce a protective antioxidant response in the heart. We found that adipocyte-to-macrophage mitochondria transfer in white adipose tissue is inhibited in murine obesity elicited by a lard-based high-fat diet, but not a hydrogenated-coconut-oil-based high-fat diet, aging, or a corn-starch diet. The long-chain fatty acids enriched in lard suppress mitochondria capture by macrophages, diverting adipocyte-derived mitochondria into the blood for delivery to other organs, such as the heart. The depletion of macrophages rapidly increased the number of adipocyte-derived mitochondria in the blood. These findings suggest that dietary lipids regulate mitochondria uptake by macrophages locally in white adipose tissue to determine whether adipocyte-derived mitochondria are released into systemic circulation to support the metabolic adaptation of distant organs in response to nutrient stress.
脂肪细胞将线粒体转移到白色和棕色脂肪组织中的巨噬细胞中,以维持代谢平衡。在肥胖中,脂肪细胞向巨噬细胞的线粒体转移受损,相反,脂肪细胞将线粒体释放到血液中,以在心脏中诱导保护性抗氧化反应。我们发现,由猪油基高脂肪饮食引起的肥胖小鼠的白色脂肪组织中的脂肪细胞向巨噬细胞的线粒体转移受到抑制,但由氢化椰子油基高脂肪饮食、衰老或玉米淀粉饮食引起的肥胖则没有受到抑制。富含猪油的长链脂肪酸抑制了巨噬细胞对线粒体的捕获,将脂肪细胞衍生的线粒体转移到血液中,输送到其他器官,如心脏。巨噬细胞耗竭后,血液中脂肪细胞衍生的线粒体数量迅速增加。这些发现表明,膳食脂质可调节白色脂肪组织中巨噬细胞对线粒体的摄取,以确定脂肪细胞衍生的线粒体是否释放到全身循环中,以支持营养应激下远处器官的代谢适应。
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