RT Journal Article
T1 DIAPH1 mediates progression of atherosclerosis and regulates hepatic lipid metabolism in mice
A1 Senatus, Laura
A1 Egaña-Gorroño, Lander
A1 López-Díez, Raquel
A1 Bergaya, Sonia
A1 Aranda Gómez, Juan Francisco
A1 Amengual, Jaume
A1 Lakshmi, Arivazhagan
A1 Manigrasso, Michaele
A1 Yepuri, Gautham
A1 Nimma, Ramesh
A1 Mangar, Kaamashri
A1 Bernadin, Rollanda
A1 Zhou, Boyan
A1 Gugger, Paul
A1 Li, Huilin
A1 Friedman, Richard
A1 Theise, Neil
A1 Shekhtman, Alexander
A1 Fisher, Edward
A1 Ramasamy Ravichandran, 
A1 Schmidt Ann Marie, 
AB Atherosclerosis evolves through dysregulated lipid metabolism interwoven with exaggerated inflammation. Previous work implicating the receptor for advanced glycation end products (RAGE) in atherosclerosis prompted us to explore if Diaphanous 1 (DIAPH1), which binds to the RAGE cytoplasmic domain and is important for RAGE signaling, contributes to these processes. We intercrossed atherosclerosis-prone Ldlr−/− mice with mice devoid of Diaph1 and fed them Western diet for 16 weeks. Compared to male Ldlr−/− mice, male Ldlr−/− Diaph1−/− mice displayed significantly less atherosclerosis, in parallel with lower plasma concentrations of cholesterol and triglycerides. Female Ldlr−/− Diaph1−/− mice displayed significantly less atherosclerosis compared to Ldlr−/− mice and demonstrated lower plasma concentrations of cholesterol, but not plasma triglycerides. Deletion of Diaph1 attenuated expression of genes regulating hepatic lipid metabolism, Acaca, Acacb, Gpat2, Lpin1, Lpin2 and Fasn, without effect on mRNA expression of upstream transcription factors Srebf1, Srebf2 or Mxlipl in male mice. We traced DIAPH1-dependent mechanisms to nuclear translocation of SREBP1 in a manner independent of carbohydrate- or insulin-regulated cues but, at least in part, through the actin cytoskeleton. This work unveils new regulators of atherosclerosis and lipid metabolism through DIAPH1.
PB Springer
SN 2399-3642
YR 2023
FD 2023
LK https://hdl.handle.net/20.500.14352/94930
UL https://hdl.handle.net/20.500.14352/94930
LA eng
NO Senatus, L., Egaña-Gorroño, L., López-Díez, R. et al. DIAPH1 mediates progression of atherosclerosis and regulates hepatic lipid metabolism in mice. Commun Biol 6, 280 (2023). https://doi.org/10.1038/s42003-023-04643-2
NO Funding for this project included: U.S. Public Health Service (P01HL146367) to AMS, AS, and RR and 1P01HL131481 (EF, AMS, and RR). Support was also provided from the Diabetes Research Program, NYU Grossman School of Medicine.Primary data are available in Supplementary Data 1–6. RNAseq data are deposited to NCBI GEO GSE156403. Any materials reported in this research are available through Material Transfer Agreement (MTA) with NYU Grossman School of Medicine.
NO U.S. Public Health Service
NO Diabetes Research Program
NO New York University
DS Docta Complutense
RD 9 abr 2025