ArticleJCI insight2023
TFEB-mediated lysosomal exocytosis alleviates high-fat diet-induced lipotoxicity in the kidney.
Article in JCI insight, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 38 papers.
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Who cites it
38 citing papers in PubMed, 46 citations in OpenAlex.
- Lipophagy: A key regulator in oxidative stress and metabolic disorders.Genes & diseases · 2026Review
- Autophagy and Mitophagy in Hypertensive Chronic Kidney Disease: Evidence Grading, Cell-Type Divergence, and a Working Lysosomal Hypothesis.Life (Basel, Switzerland) · 2026Review
- Renoprotective effects of tubular glucagon receptor activation mediated by V-ATPase.Science advances · 2026Article
- Selective autophagy in kidney health and disease.Nature reviews. Nephrology · 2026Review
- Article
- Collagen-specific molecular chaperone Hsp47 in inguinal white adipose tissue promotes high-fat diet-induced inflammatory gene expression in male mice.Scientific reports · 2026Article
- Heterogeneity in lysosomal dynamics and metabolic functions along the kidney proximal tubule.Nature communications · 2026Article
- Unraveling Lysosomal Exocytosis: From Molecular Mechanisms to Physiological Functions.Traffic (Copenhagen, Denmark) · 2026Review
- From glucosuria to dialysis: a case report of osmotic nephropathy due to an SGLT2 inhibitor.BMC nephrology · 2026Article
- Lysosomal checkpoints in renal autoimmunity: from antigen processing to metabolic-immune crosstalk.Frontiers in immunology · 2026Review
- Tubulointerstitial inflammation and fibrosis induced by proteinuria: fresh insights.Frontiers in pharmacology · 2026Review
- Multidimensional mechanisms of natural products in modulating metabolic dysfunction-associated kidney disease: recent advances and future perspectives.Frontiers in pharmacology · 2026Review
- Autophagy in kidney physiology: from cellular quality control to organ metabolism.Autophagy reports · 2026Review
- Review
- Identifying Potential Drug Targets for Membranous Nephropathy Through an Analysis of Mendelian Randomization.Cureus · 2025Article
- Narrative review of mitochondrial dysfunction in aging-related salt-sensitive hypertension: outcomes, mechanisms, and therapeutic implications.Aging advances · 2025Article
- Lysosome heterogeneity and diversity mapped through its distinct cellular functions.Cellular and molecular life sciences : CMLS · 2025Review
- One day of environment-induced heat stress causes injury to the murine kidney.Experimental physiology · 2025Article
- High-fat diet impairs intermediate-term memory by autophagic-lysosomal dysfunction in Drosophila.PLoS genetics · 2025Article
- FAF2 is a bifunctional regulator of peroxisomal homeostasis and saturated lipid responses.Science advances · 2025Article
Corrections and comments
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Authors and funding
26 authors at 9 institutions in 5 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Obesity is a major risk factor for end-stage kidney disease. We previously found that lysosomal dysfunction and impaired autophagic flux contribute to lipotoxicity in obesity-related kidney disease, in both humans and experimental animal models. However, the regulatory factors involved in countering renal lipotoxicity are largely unknown. Here, we found that palmitic acid strongly promoted dephosphorylation and nuclear translocation of transcription factor EB (TFEB) by inhibiting the mechanistic target of rapamycin kinase complex 1 pathway in a Rag GTPase-dependent manner, though these effects gradually diminished after extended treatment. We then investigated the role of TFEB in the pathogenesis of obesity-related kidney disease. Proximal tubular epithelial cell-specific (PTEC-specific) Tfeb-deficient mice fed a high-fat diet (HFD) exhibited greater phospholipid accumulation in enlarged lysosomes, which manifested as multilamellar bodies (MLBs). Activated TFEB mediated lysosomal exocytosis of phospholipids, which helped reduce MLB accumulation in PTECs. Furthermore, HFD-fed, PTEC-specific Tfeb-deficient mice showed autophagic stagnation and exacerbated injury upon renal ischemia/reperfusion. Finally, higher body mass index was associated with increased vacuolation and decreased nuclear TFEB in the proximal tubules of patients with chronic kidney disease. These results indicate a critical role of TFEB-mediated lysosomal exocytosis in counteracting renal lipotoxicity.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.