Striking membrane defects in AdipoR-deficient cells

Ruiz, Mario; Panagaki, Dimitra; Höög, Johanna L.; Pilon, Marc

doi:10.1016/j.jlr.2023.100335

Cited by 2 publications

(7 citation statements)

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“…Quantification of cytoplasm area (Figure 2J) and of the nucleus/cytoplasm (Figure 2K) as well as of the specific structures just listed (Figure 2L–Q) revealed no differences between control and AdipoR2 knockout mice, except for the three rare instances of spiral/onion‐like structures found among 46 high‐resolution neuron images (i.e., in 6.5% of examined neurons) from AdipoR2 knockout mice but never among the 36 wild‐type images. In spite of their rarity, these spiral‐like structures are mentioned because of their similarity to the structures previously observed in AdipoR2 knockout cells challenged with palmitic acid 56,67 …”

Section: Resultsmentioning

confidence: 63%

“…This is perhaps not surprising given the general health of these mice. Yet, several striking defects, including spiral‐shaped ER, swollen membranes, and nuclear envelope blebs are observed in cultured AdipoR2 knockout mouse embryonic fibroblasts 56,67 . The context of the whole mouse physiology seems to somehow protect cell membrane morphology despite the excess phospholipid SFAs.…”

Section: Discussionmentioning

confidence: 99%

“…Yet, several striking defects, including spiral-shaped ER, swollen membranes, and nuclear envelope blebs are observed in cultured AdipoR2 knockout mouse embryonic fibroblasts. 56,67 The context of the whole mouse physiology seems to somehow protect cell membrane morphology despite the excess phospholipid SFAs. Speculatively, the enlarged brain defect may be due to larger glial cells, as has been observed in C. elegans lacking EAS-1, an inhibitor of the ubiquitin ligase RNF-145.…”

Section: Discussionmentioning

confidence: 99%

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Aging AdipoR2‐deficient mice are hyperactive with enlarged brains excessively rich in saturated fatty acids

Ruiz,

Devkota,

Bergh

et al. 2024

The FASEB Journal

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To investigate how the fatty acid composition of brain phospholipids influences brain‐specific processes, we leveraged the AdipoR2 (adiponectin receptor 2) knockout mouse model in which the brain is enlarged, and cellular membranes are excessively rich in saturated fatty acids. Lipidomics analysis of brains at 2, 7, and 18 months of age showed that phosphatidylcholines, which make up about two‐thirds of all cerebrum membrane lipids, contain a gross excess of saturated fatty acids in AdipoR2 knockout mice, and that this is mostly attributed to an excess palmitic acid (C16:0) at the expense of oleic acid (C18:1), consistent with a defect in fatty acid desaturation and elongation in the mutant. Specifically, there was a ~12% increase in the overall saturated fatty acid content within phosphatidylcholines and a ~30% increase in phosphatidylcholines containing two palmitic acids. Phosphatidylethanolamines, sphingomyelins, ceramides, lactosylceramides, and dihydroceramides also showed an excess of saturated fatty acids in the AdipoR2 knockout mice while nervonic acid (C24:1) was enriched at the expense of shorter saturated fatty acids in glyceroceramides. Similar defects were found in the cerebellum and myelin sheaths. Histology showed that cell density is lower in the cerebrum of AdipoR2 knockout mice, but electron microscopy did not detect reproducible defects in the ultrastructure of cerebrum neurons, though proteomics analysis showed an enrichment of electron transport chain proteins in the cerebellum. Behavioral tests showed that older (33 weeks old) AdipoR2 knockout mice are hyperactive and anxious compared to control mice of a similar age. Also, in contrast to control mice, the AdipoR2 knockout mice do not gain weight in old age but do have normal lifespans. We conclude that an excess fatty acid saturation in brain phospholipids is accompanied by hyperactivity but seems otherwise well tolerated.

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Section: Resultsmentioning

confidence: 63%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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Aging AdipoR2‐deficient mice are hyperactive with enlarged brains excessively rich in saturated fatty acids

Ruiz,

Devkota,

Bergh

et al. 2024

The FASEB Journal

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“…[67] Similarly, primary MEFs lacking ADIPOR2 also have reduced expression of SCD and show excess SFA content in phospholipids accompanied by rigid membranes that exhibit unusual straight structures and whorls/spirals in the ER membranes (Figure 3A,B). [66,68] The development and growth rate of mouse embryos depend on the delivery of dietary lipids from the mother through the placenta. [69] Mouse mutants lacking the Mttp or FATP4 genes, which are required for transport and uptake of maternally provided lipids by the embryos, are lethal by day ∼E10.5.…”

Section: Paqrs In M Musculus and H Sapiensmentioning

confidence: 99%

Section: Paqr Proteins and Membrane Homeostasismentioning

confidence: 99%

PAQR proteins and the evolution of a superpower: Eating all kinds of fats

Pilon

Ruiz

2023

BioEssays

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Recently published work showed that members of the PAQR protein family are activated by cell membrane rigidity and contribute to our ability to eat a wide variety of diets. Cell membranes are primarily composed of phospholipids containing dietarily obtained fatty acids, which poses a challenge to membrane properties because diets can vary greatly in their fatty acid composition and could impart opposite properties to the cellular membranes. In particular, saturated fatty acids (SFAs) can pack tightly and form rigid membranes (like butter at room temperature) while unsaturated fatty acids (UFAs) form more fluid membranes (like vegetable oils). Proteins of the PAQR protein family, characterized by the presence of seven transmembrane domains and a cytosolic N‐terminus, contribute to membrane homeostasis in bacteria, yeasts, and animals. These proteins respond to membrane rigidity by stimulating fatty acid desaturation and incorporation of UFAs into phospholipids and explain the ability of animals to thrive on diets with widely varied fat composition.

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Striking membrane defects in AdipoR-deficient cells

Cited by 2 publications

References 3 publications

Aging AdipoR2‐deficient mice are hyperactive with enlarged brains excessively rich in saturated fatty acids

Aging AdipoR2‐deficient mice are hyperactive with enlarged brains excessively rich in saturated fatty acids

PAQR proteins and the evolution of a superpower: Eating all kinds of fats

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