Mesenteric adipose tissue B lymphocytes promote local and hepatic inflammation in non-alcoholic fatty liver disease mice

Mesenteric adipose tissue (MAT) inflammation is associated with non-alcoholic fatty liver disease (NAFLD), and immune cells play pivotal roles in the inflammation of adipose tissue. Here, we investigated the roles of MAT B lymphocytes in NAFLD. Mice fed with high-fat diet (HFD) and normal diet (ND) were killed in time gradients (4, 8 and 12 weeks). Compared with ND-fed mice, intra-hepatic CD45(+) CD19(+) B lymphocytes increased after 4 weeks (P < 0.01) of HFD feeding, and lasted until the 12th week, infiltrated earlier than CD45(+) CD3(+) T lymphocytes and CD45(+) F4/80(+) macrophages. The mRNA expression of tumour necrosis factor (TNF)-alpha, interleukin (IL)-6 and monocyte chemotactic protein (MCP)-1 decreased in MAT of B-null HFD-fed mice compared to that in wild-type HFD-fed mice, along with lesser macrophages. Mesenteric adipose tissue B cells from HFD-fed mice promoted macrophage differentiation to type-I macrophages and expression of pro-inflammatory cytokines in vitro. Macrophages pre-treated with MAT B cells from HFD-fed mice showed elevated mRNA expression of IL-6 and TNF-alpha and declined IL-10 levels in adipocytes compared to ND MAT B cell pre-treated macrophages. Besides, internal near-infrared scanning and external transwell assay showed that HFD MAT B cells migrated to the liver more than ND MAT B cells. High-fat diet MAT B cells induced higher MCP-1 and lower IL-10 expression in primary hepatocytes compared to ND MAT B cells in co-culture experiment. These data indicate that B lymphocytes infiltrate early in MAT during the development of NAFLD, which may not only promote MAT inflammation by regulating macrophages but also migrate to the liver and induce hepatocytes inflammation.