Involvement of the Vagus Nerve in the Anorectic Effect of Monoacylglycerol Acyltransferase 2 Inhibition in Mice

Overview

Journal Obes Sci Pract

Date 2023 Dec 13

PMID 38090688

Authors

Kosuke Takemoto

Hideaki Kato

Kenichi Higashino

Affiliations

Soon will be listed here.

Abstract

Background: Many of the drugs used for obesity treatment have adverse effects on the central nervous system. Therefore, novel treatments, such as peripherally acting drugs, are needed. Monoacylglycerol acyltransferase 2 (MGAT2), highly expressed in the small intestine, catalyzes the first step of triacylglycerol re-synthesis. MGAT2 inhibition suppresses food intake in high-fat diet (HFD)-fed mice, but the mechanisms remain unclear. Here, the involvement of the vagus nerve in MGAT2 inhibition-induced feeding suppression was investigated.

Methods: Fasted mice were administered an MGAT2 inhibitor. Food intake was measured after HFD re-feeding, and the effect of capsaicin pretreatment on changes in food intake was evaluated. The number of c-fos-positive cells in the nucleus tractus solitarius and levels of appetite regulators were determined after HFD re-feeding or lipid gavage.

Results: The anorectic effect of the MGAT2 inhibitor was abolished when vagus nerve function was interrupted by capsaicin. MGAT2 inhibition increased the number of c-fos-positive cells in the nucleus tractus solitarius and elevated intestinal oleoylethanolamide, plasma peptide tyrosine-tyrosine and plasma glucagon-like peptide-1 levels.

Conclusion: MGAT2 inhibition suppresses feeding behavior via peripheral vagus nerve signaling and may serve as a novel anti-obesity strategy with a low risk of unexpected central nervous system-related adverse effects.

Citing Articles

The Continuous and Reversible Transformation of the Polymorphs of an MGAT2 Inhibitor (S-309309) from the Anhydrate to the Hydrate in Response to Relative Humidity.

Miyano T, Sugita K, Ueda H Pharmaceutics. 2024; 16(7).

PMID: 39065646 PMC: 11280299. DOI: 10.3390/pharmaceutics16070949.

Involvement of the vagus nerve in the anorectic effect of monoacylglycerol acyltransferase 2 inhibition in mice.

Takemoto K, Kato H, Higashino K Obes Sci Pract. 2023; 9(6):601-608.

PMID: 38090688 PMC: 10712405. DOI: 10.1002/osp4.693.

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