Hepatocyte vitamin D receptor functions as a nutrient sensor that regulates energy storage and tissue growth in zebrafish.
Cell Rep
; 43(7): 114393, 2024 Jul 23.
Article
em En
| MEDLINE
| ID: mdl-38944835
ABSTRACT
Vitamin D receptor (VDR) has been implicated in fatty liver pathogenesis, but its role in the regulation of organismal energy usage remains unclear. Here, we illuminate the evolutionary function of VDR by demonstrating that zebrafish Vdr coordinates hepatic and organismal energy homeostasis through antagonistic regulation of nutrient storage and tissue growth. Hepatocyte-specific Vdr impairment increases hepatic lipid storage, partially through acsl4a induction, while simultaneously diminishing fatty acid oxidation and liver growth. Importantly, Vdr impairment exacerbates the starvation-induced hepatic storage of systemic fatty acids, indicating that loss of Vdr signaling elicits hepatocellular energy deficiency. Strikingly, hepatocyte Vdr impairment diminishes diet-induced systemic growth while increasing hepatic and visceral fat in adult fish, revealing that hepatic Vdr signaling is required for complete adaptation to food availability. These data establish hepatocyte Vdr as a regulator of organismal energy expenditure and define an evolutionary function for VDR as a transcriptional effector of environmental nutrient supply.
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Texto completo:
1
Bases de dados:
MEDLINE
Assunto principal:
Peixe-Zebra
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Receptores de Calcitriol
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Hepatócitos
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Metabolismo Energético
Limite:
Animals
Idioma:
En
Revista:
Cell Rep
Ano de publicação:
2024
Tipo de documento:
Article
País de afiliação:
Estados Unidos