Suppression of NSDHL attenuates adipogenesis with a downregulation of LXR-SREBP1 pathway in 3T3-L1 cells

• Published in: Bioscience, biotechnology, and biochemistry Vol. 84; no. 5; pp. 980 - 988
• Main Authors: Zhang, Haiyan, Li, Chengping, Xin, Youzhi, Cui, Xiao, Cui, Jianwei, Zhou, Guoli
• Format: Journal Article
• Language: English
• Published: England Taylor & Francis 03.05.2020; Oxford University Press
• Subjects: 3-Hydroxysteroid Dehydrogenases - genetics; 3T3-L1 Cells; Adipocytes - metabolism; adipogenesis; Adipogenesis - genetics; Animals; Cell Proliferation - genetics; differentiation; Down-Regulation - genetics; Gene Expression Regulation; Gene Knockdown Techniques; Lipid Metabolism - genetics; Liver X Receptors - metabolism; LXR-SREBP1 signaling pathway; Mice; NSDHL; PPAR gamma - genetics; PPAR gamma - metabolism; Signal Transduction - genetics; Sterol Regulatory Element Binding Protein 1 - metabolism; Transfection; signaling pathway; differentiation; adipogenesis; NSDHL; LXR-SREBP1 signaling pathway
• ISSN: 0916-8451; 1347-6947
• DOI: 10.1080/09168451.2020.1719823

Previous RNA-Seq analyses revealed that NAD(P)H steroid dehydrogenase-like (NSDHL) has a different expression during 3T3-L1 differentiation; however, its roles in adipogenesis are unknown. In the present study, using quantitative real-time PCR, we confirmed that NSDHL knockdown increased the proliferation of 3T3-L1 preadipocytes, but attenuated the differentiation of 3T3-L1 preadipocytes, as evidenced by reduced lipid accumulation and down-regulation of PPARγ gene expression. Further analyses showed that the expression peak of NSDHL was at the early stage of 3T3-L1 preadipocytes differentiation and LXR-SREBP1 signaling pathway was downregulated in NSDHL-knockdown 3T3-L1 cells. Collectively, our findings indicate that NSDHL is a novel modulator of adipogenesis. Moreover, our data provide insight into the complex relationships between sterol sensing, LXR-SREBP1 signaling pathway, and PPARγ in 3T3-L1 cells. Upon adipogenic induction, NSDHL increases the relative content of oxysterols, which stimulates PPARγ expression through stimulating an increase in LXR-SREBP1 pathway.