Anti-IL-17 Antibody Improves Hepatic Steatosis by Suppressing Interleukin-17-Related Fatty Acid Synthesis and Metabolism

Abstract EN

To investigate the relationship between interleukin-17 and proteins involved in fatty acid metabolism with respect to alcoholic liver disease, male ICR mice were randomized into five groups: control, alcoholic liver disease (ALD) at 4 weeks, 8 weeks, and 12 weeks, and anti-IL-17 antibody treated ALD.

A proteomic approach was adopted to investigate changes in liver proteins between control and ALD groups.

The proteomic analysis was performed by two-dimensional difference gel electrophoresis.

Spots of interest were subsequently subjected to nanospray ionization tandem mass spectrometry (MS/MS) for protein identification.

Additionally, expression levels of selected proteins were confirmed by western blot.

Transcriptional levels of some selected proteins were determined by RT-PCR.

Expression levels of 95 protein spots changed significantly (ratio >1.5, P<0.05) during the development of ALD.

Sterol regulatory element-binding protein-lc (SREBP-1c), carbohydrate response element binding protein (ChREBP), enoyl-coenzyme A hydratase (ECHS1), and peroxisome proliferator-activated receptor alpha (PPAR-α) were identified by MS/MS among the proteins shown to vary the most; increased IL-17 elevated the transcription of SREBP-1c and ChREBP but suppressed ECHS1 and PPAR-α.

The interleukin-17 signaling pathway is involved in ALD development; anti-IL-17 antibody improved hepatic steatosis by suppressing interleukin-17-related fatty acid metabolism.