PUBLICATION
Hepatocyte vitamin D receptor functions as a nutrient sensor that regulates energy storage and tissue growth in zebrafish
- Authors
- Freeburg, S.H., Shwartz, A., Kemény, L.V., Smith, C.J., Weeks, O., Miller, B.M., PenkoffLidbeck, N., Fisher, D.E., Evason, K.J., Goessling, W.
- ID
- ZDB-PUB-240701-2
- Date
- 2024
- Source
- Cell Reports 43: 114393114393 (Journal)
- Registered Authors
- Evason, Kimberley, PenkoffLidbeck, Nadia
- Keywords
- CP: Metabolism, evolution, liver, metabolism, nuclear hormone receptors, vitamin D, zebrafish
- MeSH Terms
-
- Animals
- Energy Metabolism*
- Fatty Acids/metabolism
- Hepatocytes*/metabolism
- Homeostasis
- Lipid Metabolism
- Liver/metabolism
- Nutrients/metabolism
- Receptors, Calcitriol*/metabolism
- Signal Transduction
- Zebrafish*/metabolism
- Zebrafish Proteins/genetics
- Zebrafish Proteins/metabolism
- PubMed
- 38944835 Full text @ Cell Rep.
Citation
Freeburg, S.H., Shwartz, A., Kemény, L.V., Smith, C.J., Weeks, O., Miller, B.M., PenkoffLidbeck, N., Fisher, D.E., Evason, K.J., Goessling, W. (2024) Hepatocyte vitamin D receptor functions as a nutrient sensor that regulates energy storage and tissue growth in zebrafish. Cell Reports. 43:114393114393.
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.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping