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Alx3 deficiency disrupts energy homeostasis, alters body composition, and impairs hypothalamic regulation of food intake.

Authors :
Mirasierra, Mercedes
Fernández-Pérez, Antonio
Lizarbe, Blanca
Keiran, Noelia
Ruiz-Cañas, Laura
Casarejos, María José
Cerdán, Sebastián
Vendrell, Joan
Fernández-Veledo, Sonia
Vallejo, Mario
Source :
Cellular & Molecular Life Sciences. 8/12/2024, Vol. 81 Issue 1, p1-22. 22p.
Publication Year :
2024

Abstract

The coordination of food intake, energy storage, and expenditure involves complex interactions between hypothalamic neurons and peripheral tissues including pancreatic islets, adipocytes, muscle, and liver. Previous research shows that deficiency of the transcription factor Alx3 alters pancreatic islet-dependent glucose homeostasis. In this study we carried out a comprehensive assessment of metabolic alterations in Alx3 deficiency. We report that Alx3-deficient mice exhibit decreased food intake without changes in body weight, along with reduced energy expenditure and altered respiratory exchange ratio. Magnetic resonance imaging reveals increased adiposity and decreased muscle mass, which was associated with markers of motor and sympathetic denervation. By contrast, Alx3-deficient mice on a high-fat diet show attenuated weight gain and improved insulin sensitivity, compared to control mice. Gene expression analysis demonstrates altered lipogenic and lipolytic gene profiles. In wild type mice Alx3 is expressed in hypothalamic arcuate nucleus neurons, but not in major peripheral metabolic organs. Functional diffusion-weighted magnetic resonance imaging reveals selective hypothalamic responses to fasting in the arcuate nucleus of Alx3-deficient mice. Additionally, altered expression of proopiomelanocortin and melanocortin-3 receptor mRNA in the hypothalamus suggests impaired regulation of feeding behavior. This study highlights the crucial role for Alx3 in governing food intake, energy homeostasis, and metabolic nutrient partitioning, thereby influencing body mass composition. [ABSTRACT FROM AUTHOR]

Details

Language :
English
ISSN :
1420682X
Volume :
81
Issue :
1
Database :
Academic Search Index
Journal :
Cellular & Molecular Life Sciences
Publication Type :
Academic Journal
Accession number :
178970248
Full Text :
https://doi.org/10.1007/s00018-024-05384-z