The homeodomain transcription factor Six3 regulates hypothalamic Pomc expression and its absence from POMC neurons induces hyperphagia and mild obesity in male mice
Yu H, Chiang A, Rubinstein M, Low M. The homeodomain transcription factor Six3 regulates hypothalamic Pomc expression and its absence from POMC neurons induces hyperphagia and mild obesity in male mice. Molecular Metabolism 2024, 87: 101993. PMID: 39025297, PMCID: PMC11327434, DOI: 10.1016/j.molmet.2024.101993.Peer-Reviewed Original ResearchHypothalamic POMC expressionPOMC neuronsPOMC expressionFood intakeMild obesityDaily food intakeFemale micePOMC immunoreactivityAdult micePOMC-expressing neuronsSuppress food intakeMaintenance of physiological levelsPOMC mRNA levelsReduced POMC expressionBody weightKnockout mouse modelMouse hypothalamic neuronsIncreased daily food intakeCentral melanocortinEnhanced energy expenditureExpression of Six3Functional significanceMelanocortin neuronsHypothalamic neuronsAnorexigenic neuropeptidesA mammalian tripartite enhancer cluster controls hypothalamic Pomc expression, food intake, and body weight
Rojo D, Hael C, Soria A, de Souza F, Low M, Franchini L, Rubinstein M. A mammalian tripartite enhancer cluster controls hypothalamic Pomc expression, food intake, and body weight. Proceedings Of The National Academy Of Sciences Of The United States Of America 2024, 121: e2322692121. PMID: 38652744, PMCID: PMC11067048, DOI: 10.1073/pnas.2322692121.Peer-Reviewed Original ResearchConceptsFood intakeControl of food intakeHypothalamic POMC expressionBody weight homeostasisHypothalamic arcuate neuronsConvergent evolutionary processesReporter gene expressionPurifying selectionArcuate neuronsDeletion eventsMouse genomeMolecular evolutionWeight homeostasisFemale miceAdult micePOMC expressionTranscriptional enhancersMutant miceEnhancer mutantsTranscription factorsPlacental mammalsMammalian ordersGene expressionMiceEvolutionary process