RORα and 25-Hydroxycholesterol Crosstalk Regulates Lipid Droplet Homeostasis in Macrophages.
Nuclear hormone receptors have important roles in the regulation of metabolic and inflammatory pathways. The retinoid-related orphan receptor alpha (Rorα)-deficient staggerer (sg/sg) mice display several phenotypes indicative of aberrant lipid metabolism, including dyslipidemia, and increased suscep...
| Main Authors: | , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Public Library of Science (PLoS)
2016-01-01
|
| Series: | PLoS ONE |
| Online Access: | http://europepmc.org/articles/PMC4727927?pdf=render |
| _version_ | 1828486238280089600 |
|---|---|
| author | Zewen Kelvin Tuong Patrick Lau Ximing Du Nicholas D Condon Joel M Goode Tae Gyu Oh Jeremy C Yeo George E O Muscat Jennifer L Stow |
| author_facet | Zewen Kelvin Tuong Patrick Lau Ximing Du Nicholas D Condon Joel M Goode Tae Gyu Oh Jeremy C Yeo George E O Muscat Jennifer L Stow |
| author_sort | Zewen Kelvin Tuong |
| collection | DOAJ |
| description | Nuclear hormone receptors have important roles in the regulation of metabolic and inflammatory pathways. The retinoid-related orphan receptor alpha (Rorα)-deficient staggerer (sg/sg) mice display several phenotypes indicative of aberrant lipid metabolism, including dyslipidemia, and increased susceptibility to atherosclerosis. In this study we demonstrate that macrophages from sg/sg mice have increased ability to accumulate lipids and accordingly exhibit larger lipid droplets (LD). We have previously shown that BMMs from sg/sg mice have significantly decreased expression of cholesterol 25-hydroxylase (Ch25h) mRNA, the enzyme that produces the oxysterol, 25-hydroxycholesterol (25HC), and now confirm this at the protein level. 25HC functions as an inverse agonist for RORα. siRNA knockdown of Ch25h in macrophages up-regulates Vldlr mRNA expression and causes increased accumulation of LDs. Treatment with physiological concentrations of 25HC in sg/sg macrophages restored lipid accumulation back to normal levels. Thus, 25HC and RORα signify a new pathway involved in the regulation of lipid homeostasis in macrophages, potentially via increased uptake of lipid which is suggested by mRNA expression changes in Vldlr and other related genes. |
| first_indexed | 2024-12-11T09:29:38Z |
| format | Article |
| id | doaj.art-61f2313aad8344a498cd7c54cd093eba |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-12-11T09:29:38Z |
| publishDate | 2016-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-61f2313aad8344a498cd7c54cd093eba2022-12-22T01:13:03ZengPublic Library of Science (PLoS)PLoS ONE1932-62032016-01-01111e014717910.1371/journal.pone.0147179RORα and 25-Hydroxycholesterol Crosstalk Regulates Lipid Droplet Homeostasis in Macrophages.Zewen Kelvin TuongPatrick LauXiming DuNicholas D CondonJoel M GoodeTae Gyu OhJeremy C YeoGeorge E O MuscatJennifer L StowNuclear hormone receptors have important roles in the regulation of metabolic and inflammatory pathways. The retinoid-related orphan receptor alpha (Rorα)-deficient staggerer (sg/sg) mice display several phenotypes indicative of aberrant lipid metabolism, including dyslipidemia, and increased susceptibility to atherosclerosis. In this study we demonstrate that macrophages from sg/sg mice have increased ability to accumulate lipids and accordingly exhibit larger lipid droplets (LD). We have previously shown that BMMs from sg/sg mice have significantly decreased expression of cholesterol 25-hydroxylase (Ch25h) mRNA, the enzyme that produces the oxysterol, 25-hydroxycholesterol (25HC), and now confirm this at the protein level. 25HC functions as an inverse agonist for RORα. siRNA knockdown of Ch25h in macrophages up-regulates Vldlr mRNA expression and causes increased accumulation of LDs. Treatment with physiological concentrations of 25HC in sg/sg macrophages restored lipid accumulation back to normal levels. Thus, 25HC and RORα signify a new pathway involved in the regulation of lipid homeostasis in macrophages, potentially via increased uptake of lipid which is suggested by mRNA expression changes in Vldlr and other related genes.http://europepmc.org/articles/PMC4727927?pdf=render |
| spellingShingle | Zewen Kelvin Tuong Patrick Lau Ximing Du Nicholas D Condon Joel M Goode Tae Gyu Oh Jeremy C Yeo George E O Muscat Jennifer L Stow RORα and 25-Hydroxycholesterol Crosstalk Regulates Lipid Droplet Homeostasis in Macrophages. PLoS ONE |
| title | RORα and 25-Hydroxycholesterol Crosstalk Regulates Lipid Droplet Homeostasis in Macrophages. |
| title_full | RORα and 25-Hydroxycholesterol Crosstalk Regulates Lipid Droplet Homeostasis in Macrophages. |
| title_fullStr | RORα and 25-Hydroxycholesterol Crosstalk Regulates Lipid Droplet Homeostasis in Macrophages. |
| title_full_unstemmed | RORα and 25-Hydroxycholesterol Crosstalk Regulates Lipid Droplet Homeostasis in Macrophages. |
| title_short | RORα and 25-Hydroxycholesterol Crosstalk Regulates Lipid Droplet Homeostasis in Macrophages. |
| title_sort | rorα and 25 hydroxycholesterol crosstalk regulates lipid droplet homeostasis in macrophages |
| url | http://europepmc.org/articles/PMC4727927?pdf=render |
| work_keys_str_mv | AT zewenkelvintuong roraand25hydroxycholesterolcrosstalkregulateslipiddroplethomeostasisinmacrophages AT patricklau roraand25hydroxycholesterolcrosstalkregulateslipiddroplethomeostasisinmacrophages AT ximingdu roraand25hydroxycholesterolcrosstalkregulateslipiddroplethomeostasisinmacrophages AT nicholasdcondon roraand25hydroxycholesterolcrosstalkregulateslipiddroplethomeostasisinmacrophages AT joelmgoode roraand25hydroxycholesterolcrosstalkregulateslipiddroplethomeostasisinmacrophages AT taegyuoh roraand25hydroxycholesterolcrosstalkregulateslipiddroplethomeostasisinmacrophages AT jeremycyeo roraand25hydroxycholesterolcrosstalkregulateslipiddroplethomeostasisinmacrophages AT georgeeomuscat roraand25hydroxycholesterolcrosstalkregulateslipiddroplethomeostasisinmacrophages AT jenniferlstow roraand25hydroxycholesterolcrosstalkregulateslipiddroplethomeostasisinmacrophages |