Neuronal XRN1 is Required for Maintenance of Whole-body Metabolic Homeostasis

Overview

Journal iScience

Publisher Cell Press

Date 2021 Oct 14

PMID 34646989

Citations 5

Authors

Shohei Takaoka

Akiko Yanagiya

Haytham Mohamed Aly Mohamed

Rei Higa

Takaya Abe

Ken-Ichi Inoue

Akinori Takahashi

Patrick Stoney

Tadashi Yamamoto

Affiliations

Soon will be listed here.

Abstract

Control of mRNA stability and degradation is essential for appropriate gene expression, and its dysregulation causes various disorders, including cancer, neurodegenerative diseases, diabetes, and obesity. The 5'-3' exoribonuclease XRN1 executes the last step of RNA decay, but its physiological impact is not well understood. To address this, forebrain-specific conditional knockout mice (-cKO) were generated, as 1 null mice were embryonic lethal. -cKO mice exhibited obesity with leptin resistance, hyperglycemia, hyperphagia, and decreased energy expenditure. Obesity resulted from dysregulated communication between the central nervous system and peripheral tissues. Moreover, expression of mRNAs encoding proteins that regulate appetite and energy expenditure was dysregulated in the hypothalamus of -cKO mice. Therefore, we propose that XRN1 function in the hypothalamus is critical for maintenance of metabolic homeostasis.

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