PRJNA427382
Liver macrophages regulate metabolism independently of inflammation
It is currently debated as to whether liver macrophage (LM) activation form anti- to pro-inflammatory phenotype contributes to obesity-induced metabolic diseases. Here we report that LMs do not undergo a pro-inflammatory phenotype switch with obesity-induced insulin resistance in mice and humans. Consistently, immune response related genes remained unchanged in fly immune cells (haemocytes) upon high fat feeding. However, unbiased transcriptomic analyses revealed that LMs produce non-inflammatory factors, such insulin like growth factor binding protein 7 (Igfbp7), able to directly regulate liver metabolism. Using a unique method to manipulate gene expression only in LMs in vivo, we discovered that IGFBP7 specifically produced by LMs induces lipogenesis and gluconeogenesis, two major pathways increased in metabolic diseases. This study shows that macrophages contribute to insulin resistance independently of their inflammatory status and that targeting non-inflammatory factors produced by macrophages might represent a better strategy than anti-inflammatory drugs to tackle metabolic diseases.