Related Experiment Video
Updated: Jul 2, 2026
Quantitative Analysis of Dietary Vitamin A Metabolites in Murine Ocular and Non-Ocular Tissues Using High-Performance Liquid Chromatography
Published on: December 27, 2024
All-trans retinoic acid decreases murine adipose retinol binding protein 4 production
Josep Mercader1, Nuria Granados, M Luisa Bonet
1Laboratory of Molecular Biology, Nutrition and Biotechnology, Universitat de les Illes Balears, Palma de Mallorca, Spain.
Background/Aims:
Adipose-derived retinol binding protein 4 (RBP4) might contribute to the development of insulin resistance, and therefore further knowledge of factors regulating it is of interest. Retinoic acid, the acid form of vitamin A, affects the expression of several adipokines related to insulin sensitivity in mice. Here, we sought to investigate its impact on adipose RBP4 production.
Methods:
Changes in RBP4 expression were analyzed in adipose tissues and liver of mice treated in vivo with all-trans retinoic acid (ATRA), and in 3T3-L1 adipocytes and adipocytes derived from mouse embryonic fibroblasts exposed to ATRA.
Results:
ATRA treatment in mice increased insulin sensitivity as assessed by the homeostatic model assessment for insulin resistance, and led to a reduction of RBP4 mRNA and protein levels in adipose tissues, a reduction of RBP4 protein but not RBP4 mRNA levels in the liver, and a marked increase in circulating RBP4 protein levels. In adipocyte cell models, ATRA down-regulated RBP4 mRNA levels in a dose-dependent manner: this effect was reproduced by retinaldehyde and retinoid receptors agonists, and correlated with a reduced accumulation of RBP4 protein in the culture medium.
Conclusion:
These results reveal a selective effect of ATRA inhibiting RBP4 expression specifically in adipocytes, and reinforce the concept that vitamin A vitamers may affect insulin sensitivity through effects on adipokine production.
Insights
All-trans retinoic acid (ATRA) enhances insulin sensitivity by specifically reducing adipose retinol binding protein 4 (RBP4) expression in fat cells. This highlights vitamin A
Area of Science:
- Metabolism and Endocrinology
- Nutritional Biochemistry
- Adipose Tissue Biology
Background:
- Adipose-derived retinol binding protein 4 (RBP4) is implicated in insulin resistance.
- Vitamin A metabolites, like retinoic acid, influence adipokines related to insulin sensitivity.
- Understanding RBP4 regulation is crucial for metabolic health.
Purpose of the Study:
- To investigate the impact of all-trans retinoic acid (ATRA) on adipose RBP4 production.
- To explore the relationship between ATRA, RBP4, and insulin sensitivity.
Main Methods:
- In vivo studies: ATRA treatment in mice, analyzing adipose tissue and liver RBP4 expression.
- In vitro studies: ATRA exposure to 3T3-L1 adipocytes and primary adipocytes.
- Assessed insulin sensitivity using the homeostatic model assessment for insulin resistance (HOMA-IR).
Main Results:
- ATRA treatment improved insulin sensitivity in mice.
- Adipose RBP4 mRNA and protein levels decreased following ATRA treatment.
- ATRA reduced RBP4 mRNA in adipocytes dose-dependently, with similar effects from other retinoids.
- Circulating RBP4 protein levels increased in ATRA-treated mice.
Conclusions:
- ATRA selectively inhibits RBP4 expression in adipocytes.
- Vitamin A metabolites can modulate insulin sensitivity via adipokine production.
- These findings offer insights into vitamin A's role in metabolic regulation.
