Alx3 deficiency disrupts energy homeostasis, alters body composition, and impairs hypothalamic regulation of food intake
Year: 2024
Type: article
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.
Institutions: Consejo Superior de Investigaciones Científicas, Instituto de Salud Carlos III, Instituto de Investigaciones Biomédicas Sols-Morreale, Centro de Investigación Biomédica en Red Diabetes y Enfermedades Metabólicas Asociadas, Centro de Investigación Biomédica en Red, Universidad Autónoma de Madrid, Centre for Industrial Technological Development, Institut de Recerca Biomèdica Catalunya Sud, Hospital Universitari Joan XXIII de Tarragona, Universitat Rovira i Virgili, Instituto Ramón y Cajal de Investigación Sanitaria, Hospital Universitario Ramón y Cajal
Language: English
Subfield: Endocrine and Autonomic Systems
Field: Neuroscience
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $4,290
Funders: Generalitat de Catalunya, Ministerio de Economía y Competitividad, Ministerio de Ciencia e Innovación, Universitat de Barcelona, Centro de Investigación Biomédica en Red Diabetes y Enfermedades Metabólicas Asociadas, Consejo Superior de Investigaciones Científicas, Instituto de Salud Carlos III, Agencia Estatal de Investigación
Awards: G1102667736, G143542058, G1643719742, G1822713905, G1855990336, G2064873908, G2309174360, G2330336016, G2462415295, G3005324705, G3487406020, G3518538256, G3761702578, G3851156701, G430777504, G5075480604, G5129869293, G526084217, G5421974903, G5805502524, G5913267992, G6213712056, G6219764815, G6268823086, G6619045171, G7064500655, Metabolitos como nuevos sensores energéticos. Efectos beneficiosos sobre la salud metabólica en la obesidad, comparando restricción calorica diaria vs ayuno intermitente. Estudio randomizado-cruzado., G7620767143, G8188828777, G8317322199, G8401454605, G8430294048, G8565740951
OpenAlex ID: W4401498366