Study type: In vivo/preclinical · Status: Evidence verified by machine against declared source

Modulating intestinal neuroimmune VIPergic signaling attenuates the reduction in ILC3-derived IL-22 and hepatic steatosis in MASLD.

Hepatology communications · 2024

Study scale: C57BL/6 mice were purchased from Taconic Biosciences.

Product or molecular entity relationships

VIP: Exact entity relationship. Legacy citation custody associates this source with the catalog record; no product-relevance conclusion is implied.

Public plain-language summary

The published text is limited to the declared source and preserves reported uncertainty. It does not establish efficacy, safety, suitability, or evidence strength.

Research question

Given the described hepatoprotective role of IL-22, we hypothesize that modulation of this neuroimmune circuit could potentially be an innovative approach for the control of liver steatosis.

Study design

To address this, we expressed a Designer Receptors Exclusively Activated by Designer Drugs (DREADD)-chemogenetic tool (hM4Di) in VIP-producing neurons.1832 With this tool, we promoted intermittent inhibition of VIP-producing neurons upon in vivo treatment with the DREADD agonist C21 every other day for 16 weeks during exposure to an HFD.

Participants or experimental system

We previously described that vasoactive intestinal peptide–producing neurons (VIP-neurons) regulate the efficiency of intestinal dietary fat absorption and IL-22 production by type 3 innate lymphoid cells (ILC3) in the intestine.

Study scale

C57BL/6 mice were purchased from Taconic Biosciences.

Intervention or exposure

Production of IL-22 by intestinal ILC3 is reduced in steatotic mice that were exposed to an HFD for 16 weeks.

Comparator

(A) Time course of average weight (mg) of mice placed on HFD versus ND for 16 weeks.

Outcomes examined

We characterized IL-22 production by intestinal ILC3 at this dietary endpoint.

Key findings

Metabolic dysfunction–associated steatotic liver disease (MASLD, formerly known as NAFLD) is a major driver of cirrhosis and liver-related mortality.

Limitations and uncertainty

However, therapeutic options for MASLD, including prevention of liver steatosis, are limited.

Product relevance and evidence boundary

This record is a published study, held here with its citation and review status. It is not a statement that any catalog item is effective, safe, or suitable for any use, and nothing in it is a dose or a protocol.

Evidence verified by machine against declared source. Verification is limited to the declared source and review scope. It does not mean independent replication or establish efficacy, safety, or suitability.