ArticleThe EMBO journal2019
Lipin1 deficiency causes sarcoplasmic reticulum stress and chaperone-responsive myopathy.
Article in The EMBO journal, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers.
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Who cites it
30 citing papers in PubMed, 46 citations in OpenAlex.
- Lactate Promotes Liver Regeneration by Increasing Fatty Acid Oxidation Through GCN5-Mediated H3K9 Lactylation.Cellular and molecular gastroenterology and hepatology · 2026Article
- Mitochondria-sarcoplasmic reticulum crosstalk as a modulator of skeletal muscle mass.Journal of physiology and biochemistry · 2026Review
- NLRP6 governs hippocampal microglial phagocytosis to resist stress-induced depressive-like behaviors in mice and the intervention effect of bezafibrate.Journal of advanced research · 2026Article
- Phosphatidate phosphatase Lipin1 alters mitochondria-associated endoplasmic reticulum membranes (MAMs) homeostasis: effects which contribute to the development of diabetic encephalopathy.Journal of neuroinflammation · 2025Article
- Adult-Onset Episodic Rhabdomyolysis in a Patient With a Heterozygous Lipin 1 (LPIN1) Mutation: A Case Report.Cureus · 2025Article
- Phospholipid biosynthesis modulates nucleotide metabolism and reductive capacity.Nature chemical biology · 2025Article
- Role of LIPIN 1 in regulating metabolic homeostasis in the retinal pigment epithelium.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2024Article
- Exploring lipin1 as a promising therapeutic target for the treatment of Duchenne muscular dystrophy.Journal of translational medicine · 2024Article
- Haploinsufficiency of Lipin3 leads to hypertriglyceridemia and obesity by disrupting the expression and nucleocytoplasmic localization of Lipin1.Frontiers of medicine · 2024Article
- Fibroblast Growth Factor 21: A Fascinating Perspective on the Regulation of Muscle Metabolism.International journal of molecular sciences · 2023Review
- Lipin1 plays complementary roles in myofibre stability and regeneration in dystrophic muscles.The Journal of physiology · 2023Article
- Hidden Agenda - The Involvement of Endoplasmic Reticulum Stress and Unfolded Protein Response in Inflammation-Induced Muscle Wasting.Frontiers in immunology · 2022Review
- Low lysophosphatidylcholine induces skeletal muscle myopathy that is aggravated by high-fat diet feeding.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2021Article
- Compromised mitochondrial quality control triggers lipin1-related rhabdomyolysis.Cell reports. Medicine · 2021Article
- Phospholipids: Identification and Implication in Muscle Pathophysiology.International journal of molecular sciences · 2021Review
- Myocardial Lipin 1 knockout in mice approximates cardiac effects of human LPIN1 mutations.JCI insight · 2021Article
- Epigenetic Regulation of Processes Related to High Level of Fibroblast Growth Factor 21 in Obese Subjects.Genes · 2021Article
- Metabolic Alterations in Myotonic Dystrophy Type 1 and Their Correlation with Lipin.International journal of environmental research and public health · 2021Review
- LPIN1 downregulation enhances anticancer activity of the novel HDAC/PI3K dual inhibitor FK-A11.Cancer science · 2021Article
- Acute recurrent rhabdomyolysis in a Chinese boy associated with a novel compound heterozygous LPIN1 variant: a case report.BMC neurology · 2021Article
Corrections and comments
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Authors and funding
19 authors at 11 institutions in 4 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
As a consequence of impaired glucose or fatty acid metabolism, bioenergetic stress in skeletal muscles may trigger myopathy and rhabdomyolysis. Genetic mutations causing loss of function of the LPIN1 gene frequently lead to severe rhabdomyolysis bouts in children, though the metabolic alterations and possible therapeutic interventions remain elusive. Here, we show that lipin1 deficiency in mouse skeletal muscles is sufficient to trigger myopathy. Strikingly, muscle fibers display strong accumulation of both neutral and phospholipids. The metabolic lipid imbalance can be traced to an altered fatty acid synthesis and fatty acid oxidation, accompanied by a defect in acyl chain elongation and desaturation. As an underlying cause, we reveal a severe sarcoplasmic reticulum (SR) stress, leading to the activation of the lipogenic SREBP1c/SREBP2 factors, the accumulation of the Fgf21 cytokine, and alterations of SR-mitochondria morphology. Importantly, pharmacological treatments with the chaperone TUDCA and the fatty acid oxidation activator bezafibrate improve muscle histology and strength of lipin1 mutants. Our data reveal that SR stress and alterations in SR-mitochondria contacts are contributing factors and potential intervention targets of the myopathy associated with lipin1 deficiency.
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