Abstract
Angiopoietin-like 8 (ANGPTL8) is closely linked to obesity-associated
metabolic diseases and insulin resistance. The aim of the current study was
to investigate the ability of ANGPTL8 to reverse insulin resistance in obese
mice. The administration of ANGPTL8 reduced weight gain and improved glucose
tolerance in mice with diet-induced obesity. In addition, ANGPTL8
administration modified macrophage infiltration, reduced monocyte
chemoattractant protein-1 (MCP-1) and interleukin-1β(IL-1β)
levels, and increased adiponectin gene expression in inguinal white adipose
tissue (iWAT). Moreover, the exposure of a cultured peritoneal macrophage
line to ANGPTL8 reduced the mRNA expression of M1 macrophage markers
(TNF-α and IL-1β) upon stimulation with lipopolysaccharides
in a dose-dependent manner. By contrast, when incubated with IL-4, exposure
of macrophages to ANGPTL8 increased the mRNA expression of M2 macrophage
markers (Arg1 and Chi3l3) in a dose-dependent manner. Collectively, the
results of the present study demonstrated that treatment with ANGPTL8 can
attenuate adipose tissue inflammation through regulation of macrophage
polarization, and thus, it could be useful for improving insulin
resistance.
Key words
ANGPTL8 - obesity-related inflammation - macrophage polarization - macrophage infiltration
- insulin resistance