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

Ruiz, Mario; Palmgren, Henrik; Henricsson, Marcus; Devkota, Ranjan; Jaiswal, Himjyot; Maresca, Marcello; Bohlooly‐Y, Mohammad; Peng, Xiaorong; Borén, Jan; Pilon, Marc

doi:10.1016/j.bbalip.2021.158884

Cited by 18 publications

(53 citation statements)

References 59 publications

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“…In addition, upon palmitate treatment, cells showed mitochondrial respiratory defects and poor viability [44]. Intriguingly, supplementation with mono-or polyunsaturated fatty acids, which are known to increase membrane fluidity, was able to revoke detrimental effects of AdipoR2 silencing [42,44]. These findings suggest that the primary function of AdipoRs may not be adiponectin binding but the regulation of membrane homeostasis.…”

Section: Adiponectin Receptors 1 and 2 In Regulation Of Metabolism And Membrane Homeostasismentioning

confidence: 99%

“…Furthermore, AdipoR2 downregulation in human umbilical vein endothelial cells (HUVECs) and human embryonic kidney cells (HEK293) and subsequent treatment with SFA palmitate resulted in impaired the expression of desaturases as well as the induction of unfolded protein response. In addition, upon palmitate treatment, cells showed mitochondrial respiratory defects and poor viability [44]. Intriguingly, supplementation with mono-or polyunsaturated fatty acids, which are known to increase membrane fluidity, was able to revoke detrimental effects of AdipoR2 silencing [42,44].…”

Section: Adiponectin Receptors 1 and 2 In Regulation Of Metabolism And Membrane Homeostasismentioning

confidence: 99%

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Role of Perivascular Adipose Tissue-Derived Adiponectin in Vascular Homeostasis

Sowka

Dobrzyń

2021

Cells

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Studies of adipose tissue biology have demonstrated that adipose tissue should be considered as both passive, energy-storing tissue and an endocrine organ because of the secretion of adipose-specific factors, called adipokines. Adiponectin is a well-described homeostatic adipokine with metabolic properties. It regulates whole-body energy status through the induction of fatty acid oxidation and glucose uptake. Adiponectin also has anti-inflammatory and antidiabetic properties, making it an interesting subject of biomedical studies. Perivascular adipose tissue (PVAT) is a fat depot that is conterminous to the vascular wall and acts on it in a paracrine manner through adipokine secretion. PVAT-derived adiponectin can act on the vascular wall through endothelial cells and vascular smooth muscle cells. The present review describes adiponectin’s structure, receptors, and main signaling pathways. We further discuss recent studies of the extent and nature of crosstalk between PVAT-derived adiponectin and endothelial cells, vascular smooth muscle cells, and atherosclerotic plaques. Furthermore, we argue whether adiponectin and its receptors may be considered putative therapeutic targets.

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Section: Adiponectin Receptors 1 and 2 In Regulation Of Metabolism And Membrane Homeostasismentioning

confidence: 99%

Section: Adiponectin Receptors 1 and 2 In Regulation Of Metabolism And Membrane Homeostasismentioning

confidence: 99%

Role of Perivascular Adipose Tissue-Derived Adiponectin in Vascular Homeostasis

Sowka

Dobrzyń

2021

Cells

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“…The Δ-9 desaturase SCD is responsible for converting SFA into MUFA and is essential to sustain the levels of unsaturated fatty acids required for membrane homeostasis (Devkota et al, 2017;Ruiz et al, 2021). Remarkably, an RNAseq experiment previously showed that SCD is the most robustly downregulated gene in AdipoR2-KO HEK293 cells (Ruiz et al, 2021). Likewise, in C. elegans, it has been shown that paqr-2 mutant worms have reduced expression of the SCD ortholog fat-7 (Svensk et al, 2013).…”

Section: Scd Expression and Fatty Acid Desaturation Are The Final Outputs Of The Adipor2-s1p Signalingmentioning

confidence: 99%

“…Perturbations in membrane composition and properties can have dramatic consequences for the cell/organism. For instance, lipotoxicity can often be explained by excessive membranelipid packing that in turn can be caused by a diet rich in saturated fats or by the loss of membrane regulators such as the Adiponectin Receptors (AdipoR1 and AdipoR2) (Devkota et al, 2021a;Piccolis et al, 2019;Ruiz et al, 2021;Zhu et al, 2019).…”

Section: Introductionmentioning

confidence: 99%

“…Studies in mammalian cells of different origin and in the nematode C. elegans have shown that a primary and evolutionary conserved function of the AdipoR1/2 proteins is to promote the expression of fatty acid desaturases to maintain membrane homeostasis (Pilon, 2021;Ruiz et al, 2019;Svensk et al, 2013). In particular, an RNAseq study highlighted that stearoyl-CoA desaturase (SCD) was the most robustly downregulated gene in cells lacking AdipoR2 (Ruiz et al, 2021). At the molecular level, AdipoR1/2 possess an intrinsic ceramidase activity that catalyzes the hydrolysis of ceramides to produce sphingosine and free fatty acids (Vasiliauskaite-Brooks et al, 2017).…”

Section: Introductionmentioning

confidence: 99%

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Sphingosine 1-Phosphate Mediates Adiponectin Receptor Signaling Essential For Lipid Homeostasis And Embryogenesis

Ruiz

Devkota

Panagaki

et al. 2021

Preprint

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Cells and organisms require proper membrane composition to function and develop. Phospholipids are the major component of membranes and are primarily acquired through the diet. Given great variability in diet composition, cells must be able to deploy mechanisms that correct deviations from optimal membrane composition and properties. Here, using unbiased lipidomics and proteomics, we found that the embryonic lethality in mice lacking the fluidity regulators Adiponectin Receptors 1 and 2 (AdipoR1/2) is associated with aberrant high saturation of the membrane phospholipids. Using mouse embryonic fibroblasts (MEFs) derived from AdipoR1/2-KO embryos, human cell lines and the model organism C. elegans we found that, mechanistically, AdipoR1/2-derived sphingosine 1-phosphate (S1P) signals in parallel through S1PR3-SREBP1 and PPARγ to sustain the expression of the fatty acid desaturase SCD and maintain membrane properties. Thus, our work identifies an evolutionary conserved pathway by which cells and organism maintain membrane homeostasis and adapt to a variable environment.

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A Non‐G‐Quadruplex DNA Aptamer Targeting NCL for Diagnosis and Therapy in Bladder Cancer

Liu

Pei

et al. 2023

Adv Healthcare Materials

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Bladder cancer (BC) is a highly aggressive malignant tumor affecting the urinary system, characterized by metastasis and a poor prognosis that often leads to limited therapeutic success. This study aims to develop a novel DNA aptamer for the diagnosis and treatment of BC using a tissue‐based systematic evolution of ligands by an exponential enrichment (SELEX) process. By using SELEX, this work successfully generates a new aptamer named TB‐5, which demonstrates a remarkable and specific affinity for nucleolin (NCL) in BC tissues and displays marked biocompatibility both in vitro and in vivo. Additionally, this work shows that NCL is a reliable tissue‐specific biomarker in BC. Moreover, according to circular dichroism spectroscopy, TB‐5 forms a non‐G‐quadruplex structure, distinguishing it from the current NCL–targeting aptamer AS1411, and exhibits a distinct binding region on NCL compared to AS1411. Notably, this study further reveals that TB‐5 activates NCL function by promoting autophagy and suppressing the migration and invasion of BC cells, which occurs by disrupting mRNA transcription processes. These findings highlight the critical role of NCL in the pathological examination of BC and warrant more comprehensive investigations on anti‐NCL aptamers in BC imaging and treatment.

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

Cited by 18 publications

References 59 publications

Role of Perivascular Adipose Tissue-Derived Adiponectin in Vascular Homeostasis

Role of Perivascular Adipose Tissue-Derived Adiponectin in Vascular Homeostasis

Sphingosine 1-Phosphate Mediates Adiponectin Receptor Signaling Essential For Lipid Homeostasis And Embryogenesis

A Non‐G‐Quadruplex DNA Aptamer Targeting NCL for Diagnosis and Therapy in Bladder Cancer

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