Intelectin1 ameliorates macrophage activation via inhibiting the nuclear factor kappa B pathway

Area of Science:

• Endocrinology
• Immunology
• Metabolic Syndrome Research

Background:

• Intelectin-1 (ITLN1) is an adipokine with decreased expression in diabetes and obesity.
• Mechanisms of ITLN1 production and function remain controversial.
• ITLN1 plays a role in metabolic health and inflammation.

Purpose of the Study:

• To investigate the impact of a high-fat, high-carbohydrate diet (HFHCD) on ITLN1 synthesis in the intestine.
• To elucidate the role of endoplasmic reticulum (ER) stress in regulating ITLN1 expression.
• To determine the effects of ITLN1 on macrophage activation and inflammatory pathways.

Main Methods:

• Mice were fed a HFHCD for 8 weeks to induce ER stress and alter ITLN1 expression.
• In vitro studies examined ITLN1 interaction with adiponectin receptor 1 and its effect on macrophage signaling.
• Chemical chaperones were used to reduce ER stress and assess ITLN1 restoration.

Main Results:

• HFHCD feeding increased intestinal ER stress, inhibited ITLN1 expression in intestinal endocrine cells, and lowered circulating ITLN1 levels.
• Reducing ER stress restored ITLN1 expression in HFHCD-fed mice.
• ITLN1 interacted with adiponectin receptor 1, suppressing pro-inflammatory cytokine production and macrophage phagocytosis via the NF-κB pathway.

Conclusions:

• Diet-induced ER stress reduces circulating ITLN1 by inhibiting intestinal synthesis.
• Decreased ITLN1 levels may enhance pro-inflammatory cytokine expression and macrophage activation.
• Reduced ITLN1 exacerbates chronic inflammation associated with metabolic syndrome.