AdipoR1 and AdipoR2 maintain membrane fluidity in most human cell types and independently of adiponectin

Abstract

The FA composition of phospholipids must be tightly regulated to maintain optimal cell membrane properties and compensate for a highly variable supply of dietary FAs. Previous studies have shown that AdipoR2 and its homologue PAQR-2 are important regulators of phospholipid FA composition in HEK293 cells and Caenorhabditiselegans, respectively. Here we show that both AdipoR1 and AdipoR2 are essential for sustaining desaturase expression and high levels of unsaturated FAs in membrane phospholipids of many human cell types, including primary human umbilical vein endothelial cells, and for preventing membrane rigidification in cells challenged with exogenous palmitate, a saturated FA. Three independent methods confirm the role of the AdipoRs as regulators of membrane composition and fluidity: fluorescence recovery after photobleaching, measurements of Laurdan dye generalized polarization, and mass spectrometry to determine the FA composition of phospholipids. Furthermore, we show that the AdipoRs can prevent lipotoxicity in the complete absence of adiponectin, their putative ligand. We propose that the primary cellular function of AdipoR1 and AdipoR2 is to maintain membrane fluidity in most human cell types and that adiponectin is not required for this function.

Leveraging a gain-of-function allele of Caenorhabditis elegans paqr-1 to elucidate membrane homeostasis by PAQR proteins

“…In either case, it is interesting to test whether this relationship is conserved between the human AdipoR1 and AdipoR2. For this purpose, we turned to HEK293 cells where the AdipoR1 and AdipoR2 proteins act as functional homologs of PAQR-2 and are required to prevent membrane rigidification when the cells are cultivated in the presence of palmitic acid [ 13 – 16 , 35 ]. Here, we found that overexpression of either AdipoR1 or AdipoR2 in HEK293 cells is sufficient to prevent membrane rigidification in HEK293 cells challenged with 400 μM palmitic acid ( Fig 5A–5E ).…”

“…In eukaryotes, the SREBPs are regulated by the availability of specific lipids such as cholesterol in the ER membrane [8], PCYT1A is activated by association with packing defects in the inner nuclear membrane [9][10][11] and IRE1 is activated by multimerization in response to membrane thickening in the ER [1,12]. Recently we identified a novel regulator of membrane homeostasis in animal cells, namely the PAQR-2/IGLR-2 complex in the nematode C. elegans [13][14][15][16][17][18]. The present work helps define the structure-functional basis of fluidity sensing by this complex.…”

“…Recently we identified a novel regulator of membrane homeostasis in animal cells, namely the PAQR-2/IGLR-2 complex in the nematode C . elegans [ 13 – 18 ]. The present work helps define the structure-functional basis of fluidity sensing by this complex.…”

Roles of Adiponectin Signaling Related Proteins in Mammary Tumor Development

“…[1][2][3][4][5][6] A recent study showed that both adiponectin receptors are involved in regulating cell membrane fluidity in cancer cells. [7] There are two main adiponectin receptors, adiponectin receptor-1 (AdipoR1) and adiponectin receptor-2 (AdipoR2), that have been identified and their expression has been reported in numerous tissues, such as the endometrium, brain and breast tissues obtained from both in humans and animals. [3,[6][7][8][9][10][11] On the other hand, both of adiponectin receptors' expression has also been reported in cancer cell lines and tissues, including breast cancer and endometrial cancer, in which expression of AdipoR1 was shown to be higher compared to that of AdipoR2.…”

“…[7][8][9][12][13][14] For example, adiponectin receptors mRNA expression levels were shown in the human mammary tumor, pancreatic, lung and endometrial cell lines. [7][8][9][11][12][13][14] It was reported that adiponectin functions through its receptors via modification of inflammatory signaling molecules, including Erk1/2, Akt, TNFa, IL-1b, NFkB, IL6, IL-8 and MCP1. [14] Another main target for adiponectin protein is liver tissue where it is survival and apoptotic effects were observed in hepatic cells.…”