PUBLICATION
Postnatal triglyceride accumulation is regulated by the mineralocorticoid receptor under basal and stress conditions
- Authors
- Faught, E., Vijayan, M.M.
- ID
- ZDB-PUB-190629-3
- Date
- 2019
- Source
- The Journal of physiology 597(19): 4927-4941 (Journal)
- Registered Authors
- Faught, Erin, Vijayan, Mathilakath
- Keywords
- none
- MeSH Terms
-
- Adipocytes
- Adipogenesis
- Animals
- Gene Deletion
- Gene Expression Regulation/drug effects
- Hydrocortisone/pharmacology*
- Larva
- Lipid Metabolism
- Receptors, Glucocorticoid/genetics
- Receptors, Glucocorticoid/metabolism*
- Receptors, Mineralocorticoid/agonists*
- Stress, Physiological*
- Triglycerides/metabolism*
- Up-Regulation
- Zebrafish
- PubMed
- 31246274 Full text @ J. Physiol.
Citation
Faught, E., Vijayan, M.M. (2019) Postnatal triglyceride accumulation is regulated by the mineralocorticoid receptor under basal and stress conditions. The Journal of physiology. 597(19):4927-4941.
Abstract
Key points Glucocorticoids (GCs) either enhance or reduce obesity in mammals, but limited information exists on the role of corticosteroid receptors in mediating GCs effect on lipid metabolism during postnatal development. Mineralocorticoid receptor (MR) activation leads to triglyceride (TG) accumulation post-feeding, whereas glucocorticoid receptor (GR) activation reduces TG levels. The TG profile was inversely related to the lipoprotein lipase (lpl) transcript abundance, and this gene was downregulated by MR activation. Cortisol plays an important role in adipogenesis during postnatal development in zebrafish, and this includes gene/pathway-specific signalling by GR, MR, and GR/MR interactions. Ubiquitous MR and GR knockout in zebrafish provides an excellent model to study the mode of action of GCs in regulating lipid metabolism.
Abstract Glucocorticoids (GCs) act through two receptors, the mineralocorticoid receptor (MR) and the glucocorticoid receptor (GR), which differ in both their affinity to bind GCs and their function. As MR has 10-fold higher affinity for GCs compared to GR, it has been postulated that MR activation occurs at basal levels, while stress levels of these steroid hormones activate GR signalling. There is a growing body of evidence that both these receptors are involved in GC-mediated lipid metabolism. However, the role of GCs in lipogenesis and lipolysis is controversial, as these steroids appear to both enhance and reduce obesity. As lipid synthesis is a critical part of early development, we hypothesized that both MR and GR contribute to lipid regulation by GCs during postnatal growth. Using MR and GR knockout zebrafish, we demonstrate that MR, but not GR, is involved in triglyceride (TG) accumulation during the larval development post-feeding. Lack of MR did not affect the gene expression of fatty acid synthase (fas), or acyl-CoA:diacylglycerol acyltransferase 2 (dgat2), but increased lipoprotein lipase (lpl) transcript abundance. Activation of GR with exogenous cortisol decreased TG levels and increased lpl mRNA levels, but these responses require the presence of MR. Larval transcriptome revealed that MR was the primary regulator of genes involved in lipid synthesis, while GR activation favoured lipid catabolism. Our results underscore a key role for MR signalling in mediating postnatal lipid accumulation, as well as cooperatively regulating GR-mediated lipolysis during postnatal stress. This article is protected by copyright. All rights reserved.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping