Dataset Information

Retinoic acid induces white adipose tissue browning by increasing adipose vascularity and inducing beige adipogenesis of PDGFR?+ adipose progenitors.

ABSTRACT: Formation of beige adipocytes within white adipose tissue enhances energy expenditure, which is a promising strategy to reduce obesity and prevent metabolic symptoms. Vitamin A and its bioactive metabolite, retinoic acid (RA), have regulatory roles in lipid metabolism. Here we report that RA induces white adipose tissue browning via activating vascular endothelial growth factor (VEGF) signaling. RA triggered angiogenesis and elicited de novo generation of platelet-derived growth factor receptor ? positive (PDGFR?+) adipose precursor cells via VEGFA/VEGFR2 signaling. In addition, RA promoted beige/brown adipocyte formation from capillary networks in vitro. Using PDGFR? tracking mice, we found that the vascular system acted as an adipogenic repository by containing PDGFR?+ progenitors which differentiated into beige adipocytes under RA or VEGF164 treatments. Conditional knockout of VEGF receptors blocked RA-stimulated white adipose tissue browning. Moreover, the VEGFA and RA activated p38MAPK to enhance the binding of RA receptor to RA response elements of the Prdm16 promoter and upregulated Prdm16 transcription. In conclusion, RA induces white adipose tissue browning by increasing adipose vascularity and promoting beige adipogenesis of PDGFR?+ adipose progenitors.

SUBMITTER: Wang B

PROVIDER: S-EPMC5633810 | biostudies-other | 2017

REPOSITORIES: biostudies-other

ACCESS DATA

Publications

Retinoic acid induces white adipose tissue browning by increasing adipose vascularity and inducing beige adipogenesis of PDGFRα<sup>+</sup> adipose progenitors.

Wang Bo B Fu Xing X Liang Xingwei X Deavila Jeanene M JM Wang Zhixiu Z Zhao Liang L Tian Qiyu Q Zhao Junxing J Gomez Noe Alberto NA Trombetta Sophie C SC Zhu Mei-Jun MJ Du Min M

Cell discovery 20171010

Formation of beige adipocytes within white adipose tissue enhances energy expenditure, which is a promising strategy to reduce obesity and prevent metabolic symptoms. Vitamin A and its bioactive metabolite, retinoic acid (RA), have regulatory roles in lipid metabolism. Here we report that RA induces white adipose tissue browning via activating vascular endothelial growth factor (VEGF) signaling. RA triggered angiogenesis and elicited <i>de novo</i> generation of platelet-derived growth factor re ...[more]

PMID: 29021914

Similar Datasets

Project description:BackgroundThe enrichment of peri-cancerous adipose tissue is a distinctive feature of colorectal cancer (CRC), accelerating disease progression and worsening prognosis. The communication between tumor cells and adjacent adipocytes plays a crucial role in CRC advancement. However, the precise regulatory mechanisms are largely unknown. This study aims to explore the mechanism of migration and invasion inhibitory protein (MIIP) downregulation in the remodeling of tumor cell-adipocyte communication and its role in promoting CRC.ResultsMIIP expression was found to be decreased in CRC tissues and closely associated with adjacent adipocyte browning. In an in vitro co-culture model, adipocytes treated with MIIP-downregulated tumor supernatant exhibited aggravated browning and lipolysis. This finding was further confirmed in subcutaneously allografted mice co-injected with adipocytes and MIIP-downregulated murine CRC cells. Mechanistically, MIIP interacted with the critical lipid mobilization factor AZGP1 and regulated AZGP1's glycosylation status by interfering with its association with STT3A. MIIP downregulation promoted N-glycosylation and over-secretion of AZGP1 in tumor cells. Subsequently, AZGP1 induced adipocyte browning and lipolysis through the cAMP-PKA pathway, releasing free fatty acids (FFAs) into the microenvironment. These FFAs served as the primary energy source, promoting CRC cell proliferation, invasion, and apoptosis resistance, accompanied by metabolic reprogramming. In a tumor-bearing mouse model, inhibition of β-adrenergic receptor or FFA uptake, combined with oxaliplatin, significantly improved therapeutic efficacy in CRC with abnormal MIIP expression.ConclusionsOur data demonstrate that MIIP plays a regulatory role in the communication between CRC and neighboring adipose tissue by regulating AZGP1 N-glycosylation and secretion. MIIP reduction leads to AZGP1 oversecretion, resulting in adipose browning-induced CRC rapid progression and poor prognosis. Inhibition of β-adrenergic receptor or FFA uptake, combined with oxaliplatin, may represent a promising therapeutic strategy for CRC with aberrant MIIP expression.

Dataset Information

Retinoic acid induces white adipose tissue browning by increasing adipose vascularity and inducing beige adipogenesis of PDGFR?+ adipose progenitors.

Publications

Retinoic acid induces white adipose tissue browning by increasing adipose vascularity and inducing beige adipogenesis of PDGFRα<sup>+</sup> adipose progenitors.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets