Deletion of miR-130b/301b cluster promotes macrophage efferocytosis and resolution of adipose tissue inflammation.

Macrophage efferocytosis, the clearance of apoptotic cells, is essential for tissue homeostasis and preventing inflammation. Impaired efferocytosis contributes to chronic inflammatory conditions, including obesity. However, its key regulators remain unclear. MicroRNA-130b (miR-130b) is increased in adipose tissue macrophages of individuals with obesity. Here, we found that miR-130b was enriched in bone marrow of mice, and its expression in bone marrow-derived macrophages was suppressed by IL-4 and by apoptotic cell uptake. Deletion of the miR-130b and its cluster member miR-301b enhanced macrophage efferocytosis in vitro and apoptotic cell clearance in vivo, accompanied by increased mitochondrial respiration and anti-inflammatory polarization. In high fat diet-fed mice, global deletion of miR-130b/301b reduced inflammatory gene expression in adipose tissues. Mechanistically, miR-130b suppressed PPARγ and PGC-1α, regulators of mitochondrial metabolism and inflammation, and miR-130b/301b deletion increased CX3CR1, a receptor for apoptotic cell "find me" signals. Together, miR-130b/301b deletion promotes macrophage efferocytosis and resolves adipose tissue inflammation.