The transcription factor RXRA regulates lipid metabolism in duck myoblasts by the CD36 network

Abstract

Lipid metabolism is a highly complex metabolic process regulated at multiple levels. RXRA is a well-characterized factor that regulates lipid metabolism. To explore the function and mechanism of the transcription factor RXRA in myoblasts, and to further explore the key factors that RXRA regulates the target gene CD36 signaling network to regulate lipid metabolism. We found that the transcription factor RXRA inhibited the accumulation of triglycerides (TGs), cholesterol (CHOL) and non-esterified fatty acids (NEFA) in CS2 cells by regulating CD36 as well as the fatty acid beta oxidation pathway. CD36 functions similar to RXRA in myoblasts. CD36 overexpression reduced the levels of TGs, CHOL, NEFAs and saturated fatty acids (SFAs) in these cells, while CD36 knockout increased the levels of TGs, CHOL, NEFAs, SFAs and monounsaturated fatty acids (MUPAs) in these cells. GRB2, MAP1B, SLC38A1, SLC4A7, NCOA3, PKIA, MOB2, SAA2 and RXRA are involved in the CD36 promotion of lipid efflux through lipid metabolism, endocytosis and amino acid metabolism. Considering these results, we propose that RXRA regulates lipid metabolism in myoblasts by regulating the CD36 signaling network.

Inference of differential key regulatory networks and mechanistic drug repurposing candidates from scRNA-seq data with SCANet

“…The GRN of the gene module with the strongest correlation to ISC in HFHSD (M4) revealed a genetic program controlled by four TFs (RXRA, NR1D1, SREBF1/SREBP-1, and RORC), all known regulators of lipid metabolism ( Fig. 4C ) ( Crewe et al 2019 , Hunter et al 2021 , Pan et al 2022 , Zou et al 2022 ). To explore potential drug targets specific for altered ISC mechanisms that underlie intestinal maladaptation and contribute to the development of obesity and prediabetes ( Aliluev et al 2021 ), the same module was selected for GCN–drug interactions (correlation ≥ 0.8) ( Fig.…”