ArticleNature metabolism2024
PAQR4 regulates adipocyte function and systemic metabolic health by mediating ceramide levels.
Article in Nature metabolism, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.
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Who cites it
11 citing papers in PubMed.
- Comprehensive metabolite profiling in fruits of differentFood chemistry: X · 2026Article
- E4BP4 safeguards brown fat mitochondria from obesity-induced fragmentation via ceramide repression.EMBO reports · 2026Article
- Cardiac Lipid Metabolism: Cells, Metabolites, and Rhythms.Circulation research · 2026Review
- Inhibition of ceramide synthesis ameliorates body wasting in a cancer cachexia model.The Journal of clinical investigation · 2026Article
- Induction of Yin Yang 1 (YY1) overexpression in mature adipocytes promotes dysfunctional adipose tissue and systemic insulin resistance in mice.Metabolism: clinical and experimental · 2026Article
- Genetic variation shapes the chromatin accessibility landscape and transcriptional responses in mouse adipose tissue.PLoS genetics · 2026Article
- Ceramide signaling in immunity: a molecular perspective.Lipids in health and disease · 2025Review
- Fecal Microbiota Transplantation from Mice Receiving Magnetic Mitohormesis Treatment Reverses High-Fat Diet-Induced Metabolic and Osteogenic Dysfunction.International journal of molecular sciences · 2025Article
- Regulation of the terminal complement cascade in adipose tissue for control of its volume, cellularity, and fibrosis.Obesity (Silver Spring, Md.) · 2025Review
- Puerarin Targets HIF-1α to Modulate Hypoxia-Related Sphingolipid Metabolism in Diabetic Hepatopathy via the SPTLC2/Ceramide Pathway.Pharmaceuticals (Basel, Switzerland) · 2025Article
- Higher BMI and extraversion are associated with greater button-press force in a lab setting.Frontiers in public health · 2025Article
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Authors and funding
18 authors.
Funding
Abstract
PAQR4 is an orphan receptor in the PAQR family with an unknown function in metabolism. Here, we identify a critical role of PAQR4 in maintaining adipose tissue function and whole-body metabolic health. We demonstrate that expression of Paqr4 specifically in adipocytes, in an inducible and reversible fashion, leads to partial lipodystrophy, hyperglycaemia and hyperinsulinaemia, which is ameliorated by wild-type adipose tissue transplants or leptin treatment. By contrast, deletion of Paqr4 in adipocytes improves healthy adipose remodelling and glucose homoeostasis in diet-induced obesity. Mechanistically, PAQR4 regulates ceramide levels by mediating the stability of ceramide synthases (CERS2 and CERS5) and, thus, their activities. Overactivation of the PQAR4-CERS axis causes ceramide accumulation and impairs adipose tissue function through suppressing adipogenesis and triggering adipocyte de-differentiation. Blocking de novo ceramide biosynthesis rescues PAQR4-induced metabolic defects. Collectively, our findings suggest a critical function of PAQR4 in regulating cellular ceramide homoeostasis and targeting PAQR4 offers an approach for the treatment of metabolic disorders.
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