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ELEVATED ADIPOCYTE MEMBRANE PHOSPHOLIPID SATURATION DOES NOT COMPROMISE INSULIN SIGNALING

Version 2 2023-01-12, 18:30
Version 1 2022-12-29, 18:34
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posted on 2023-01-12, 18:30 authored by Henrik Palmgren, Kasparas Petkevicius, Stefano Bartesaghi, Andrea Ahnmark, Mario Ruiz, Ralf Nilsson, Lars Löfgren, Matthew S. Glover, Anne-Christine Andréasson, Liselotte Andersson, Cécile Becquart, Michael Kurczy, Bengt Kull, Simonetta Wallin, Daniel Karlsson, Sonja Hess, Marcello Maresca, Mohammad Bohlooly-Y, Xiao-Rong Peng, Marc Pilon

Increased saturated fatty acid levels in membrane phospholipids have been implicated in the development of metabolic disease. Here, we tested the hypothesis that increased saturated fatty acid (SFA) content in cell membranes negatively impacts adipocyte insulin signaling. Pre-adipocyte cell models with elevated SFA levels in phospholipids were generated by disrupting the ADIPOR2 locus, which resulted in a striking two-fold increase in SFA-containing phosphatidylcholines and phosphatidylethanolamines, which persisted in differentiated adipocytes. Similar changes in phospholipid composition were observed in white adipose tissues isolated from the ADIPOR2 knockout mice. The SFA levels in phospholipids could be further increased by treating ADIPOR2-deficient cells with palmitic acid and resulted in reduced membrane fluidity and endoplasmic reticulum stress in mouse and human pre-adipocytes. Strikingly, increased SFA levels in differentiated adipocyte phospholipids had no effect on adipocyte gene expression or insulin signaling in vitro. Similarly, increased adipocyte phospholipid saturation did not impair white adipose tissue function in vivo, even in mice fed a high saturated fat diet at thermoneutrality. We conclude that increasing SFA levels in adipocyte phospholipids is well tolerated and does not affect adipocyte insulin signaling in vitro and in vivo.

Funding

This project has received funding from Stiftelsen för Strategisk Forskning (ID16-0049)

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