ArticleeLife2022
Reducing lipid bilayer stress by monounsaturated fatty acids protects renal proximal tubules in diabetes.
Article in eLife, 2022. 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, 47 citations in OpenAlex.
- Imbalance of mitochondria and abnormalities in lipid metabolism in Diabetic Tubulopathy.Annals of medicine · 2026Review
- Apical proximal tubule fatty acid uptake-generated ceramides cause endoplasmic reticulum stress from altered membrane fluidity.JCI insight · 2026Article
- Optical photothermal infrared imaging of fatty acid esterification in the ER of living cells.Science advances · 2026Article
- Lysosome-derived methylated arginine is a signalling metabolite controlling the lipidome.Nature cell biology · 2026Article
- Optical photothermal infrared imaging of fatty acid esterification in the ER of living cells.bioRxiv : the preprint server for biology · 2026Article
- Dietary glucuronolactone alleviates hepatic lipid accumulation via the enterohepatic axis in laying hens.Journal of animal science and biotechnology · 2026Article
- Advances regarding the mechanism of endoplasmic reticulum stress in diabetic kidney disease and pharmacological interventions (Review).Molecular medicine reports · 2026Review
- Therapeutic remodeling of the ceramide backbone prevents kidney injury.Cell metabolism · 2026Article
- Protein S-acylation: Pathological mechanisms and novel therapeutic targets for diabetic complications.Chinese herbal medicines · 2026Review
- Desaturase-dependent secretory functions of hepatocyte-like cells control systemic lipid metabolism during starvation in Drosophila.Nature communications · 2025Article
- The lipidome of the kidney tubules of ob/ob mice is affected at the infralesional level.Cell death discovery · 2025Article
- Lipid droplet dynamics in type 2 diabetes and its complications: pathophysiological insights and therapeutic options.Lipids in health and disease · 2025Review
- Article
- FATP1-mediated fatty acid uptake in renal tubular cells as a countermeasure for hypothermia.Journal of molecular medicine (Berlin, Germany) · 2025Article
- AMPK protects proximal tubular epithelial cells from lysosomal dysfunction and dedifferentiation induced by lipotoxicity.Autophagy · 2025Article
- Article
- Differential transport pathways of saturated and unsaturated fatty acid esters in male mouse hepatocytes.Nature communications · 2025Article
- N88S seipin-related seipinopathy is a lipidopathy associated with loss of iron homeostasis.Cell communication and signaling : CCS · 2025Article
- β-catenin-inhibited Sumoylation modification of LKB1 and fatty acid metabolism is critical in renal fibrosis.Cell death & disease · 2024Article
- Dynamic Adhesive Behavior and Biofilm Formation ofMaterials (Basel, Switzerland) · 2024Article
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Authors and funding
12 authors at 3 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
In diabetic patients, dyslipidemia frequently contributes to organ damage such as diabetic kidney disease (DKD). Dyslipidemia is associated with both excessive deposition of triacylglycerol (TAG) in lipid droplets (LDs) and lipotoxicity. Yet, it is unclear how these two effects correlate with each other in the kidney and how they are influenced by dietary patterns. By using a diabetes mouse model, we find here that high-fat diet enriched in the monounsaturated oleic acid (OA) caused more lipid storage in LDs in renal proximal tubular cells (PTCs) but less tubular damage than a corresponding butter diet with the saturated palmitic acid (PA). This effect was particularly evident in S2/S3 but not S1 segments of the proximal tubule. Combining transcriptomics, lipidomics, and functional studies, we identify endoplasmic reticulum (ER) stress as the main cause of PA-induced PTC injury. Mechanistically, ER stress is caused by elevated levels of saturated TAG precursors, reduced LD formation, and, consequently, higher membrane order in the ER. Simultaneous addition of OA rescues the cytotoxic effects by normalizing membrane order and increasing both TAG and LD formation. Our study thus emphasizes the importance of monounsaturated fatty acids for the dietary management of DKD by preventing lipid bilayer stress in the ER and promoting TAG and LD formation in PTCs.
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