A Multiorgan Map of Metabolic, Signaling, and Inflammatory Pathways That Coordinately Control Fasting Glycemia in Mice

Overview

Journal iScience

Publisher Cell Press

Date 2024 Nov 7

PMID 39507247

Authors

Florence Mehl

Ana Rodriguez Sanchez-Archidona

Ida Meitil

Mathias Gerl

Celine Cruciani-Guglielmacci

Leonore Wigger

Herve Le Stunff

Kelly Meneyrol

Justine Lallement

Jessica Denom

Christian Klose

Kai Simons

Marco Pagni

Christophe Magnan

Mark Ibberson

Bernard Thorens

Affiliations

Soon will be listed here.

Abstract

To identify the pathways that are coordinately regulated in pancreatic β cells, muscle, liver, and fat to control fasting glycemia we fed C57Bl/6, DBA/2, and Balb/c mice a regular chow or a high fat diet for 5, 13, and 33 days. Physiological, transcriptomic and lipidomic data were used in a data fusion approach to identify organ-specific pathways linked to fasting glycemia across all conditions investigated. In pancreatic islets, constant insulinemia despite higher glycemic levels was associated with reduced expression of hormone and neurotransmitter receptors, OXPHOS, cadherins, integrins, and gap junction mRNAs. Higher glycemia and insulin resistance were associated, in muscle, with decreased insulin signaling, glycolytic, Krebs' cycle, OXPHOS, and endo/exocytosis mRNAs; in hepatocytes, with reduced insulin signaling, branched chain amino acid catabolism and OXPHOS mRNAs; in adipose tissue, with increased innate immunity and lipid catabolism mRNAs. These data provide a resource for further studies of interorgan communication in glucose homeostasis.

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