Extensive transcription mis-regulation and membrane defects in AdipoR2-deficient cells challenged with saturated fatty acids

Ruiz, Mario,1984Gothenburg University,Göteborgs universitet,Institutionen för kemi och molekylärbiologi,Department of Chemistry and Molecular Biology (author)

How cells maintain vital membrane lipid homeostasis while obtaining most of their constituent fatty acids from a varied diet remains largely unknown. Here, we used transcriptomics, lipidomics, growth and respiration assays, and membrane property analyses in human HEK293 cells or human umbilical vein endothelial cells (HUVEC) to show that the function of AdipoR2 is to respond to membrane rigidification by regulating many lipid metabolism genes. We also show that AdipoR2-dependent membrane homeostasis is critical for growth and respiration in cells challenged with saturated fatty acids. Additionally, we found that AdipoR2 deficiency causes transcriptome and cell physiological defects similar to those observed in SREBP-deficient cells upon SFA challenge. Finally, we compared several genes considered important for lipid homeostasis, namely AdipoR2, SCD, FADS2, PEMT and ACSL4, and found that AdipoR2 and SCD are the most important among these to prevent membrane rigidification and excess saturation when human cells are challenged with exogenous SFAs. We conclude that AdipoR2-dependent membrane homeostasis is one of the primary mechanisms that protects against exogenous SFAs.

Palmgren, H. (author)
Henricsson, Marcus,1975Gothenburg University,Göteborgs universitet,Wallenberglaboratoriet,Institutionen för medicin, avdelningen för molekylär och klinisk medicin,Wallenberg Laboratory,Institute of Medicine, Department of Molecular and Clinical Medicine(Swepub:gu)xstahm (author)
Devkota, RanjanGothenburg University,Göteborgs universitet,Institutionen för kemi och molekylärbiologi,Department of Chemistry and Molecular Biology(Swepub:gu)xdevra (author)
Jaiswal, H. (author)
Maresca, M. (author)
Bohlooly-Y, M. (author)
Peng, X. R. (author)
Borén, Jan,1963Gothenburg University,Göteborgs universitet,Institutionen för medicin, avdelningen för molekylär och klinisk medicin,Institute of Medicine, Department of Molecular and Clinical Medicine(Swepub:gu)xborej (author)
Pilon, Marc,1966Gothenburg University,Göteborgs universitet,Institutionen för kemi och molekylärbiologi,Department of Chemistry and Molecular Biology(Swepub:gu)xpilom (author)
Göteborgs universitetInstitutionen för kemi och molekylärbiologi (creator_code:org_t)

In:Biochimica Et Biophysica Acta-Molecular and Cell Biology of Lipids: Elsevier BV1866:41388-1981

By the author/editor: Ruiz, Mario, 198 ...; Palmgren, H.; Henricsson, Marc ...; Devkota, Ranjan; Jaiswal, H.; Maresca, M.; show more...; Bohlooly-Y, M.; Peng, X. R.; Borén, Jan, 1963; Pilon, Marc, 196 ...; show less...

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