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

ABSTRACT: 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)-?, 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-? 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-? 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.

SUBMITTER: Wu Z 

PROVIDER: S-EPMC6484337 | biostudies-literature | 2019 May

REPOSITORIES: biostudies-literature