ArticleJournal of the American Society of Nephrology : JASN2013
Obesity-mediated autophagy insufficiency exacerbates proteinuria-induced tubulointerstitial lesions.
Article in Journal of the American Society of Nephrology : JASN, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 123 papers, 2 of them syntheses that pooled it.
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Who cites it
123 citing papers in PubMed, 2 syntheses or guidelines pooled it, 210 citations in OpenAlex.
- Beneficial effects of cell-derived exosomes on diabetic nephropathy: a systematic review and meta-analysis of preclinical evidence.Acta diabetologica · 2025Pooled it
- Evolutionary patterns and research frontiers in autophagy in podocytopathies: a bibliometric analysis.Frontiers in medicine · 2024Pooled it
- Autophagy and metabolic homeostasis: Exploration in obesity‑related metabolic diseases (Review).International journal of molecular medicine · 2026Review
- Sodium-glucose cotransporter 2 inhibitor ameliorates podocyte hypertrophic stress by suppressing the mTOR/p70S6K/cyclin D1 signaling pathway in obesity-related nephropathy.Scientific reports · 2026Article
- Autophagy in kidney physiology: from cellular quality control to organ metabolism.Autophagy reports · 2026Review
- Autophagy-senescence interplay in kidney disease: mechanistic insights and therapeutic potential.Molecular biology reports · 2025Review
- Maternal obesity promotes impaired renal autophagic process and kidney injury in male offspring.International journal of obesity (2005) · 2025Article
- Extracellular vesicles derived from mesenchymal stem cells alleviate renal fibrosis via the miR-99b-5p/mTOR/autophagy axis in diabetic kidney disease.Stem cell research & therapy · 2025Article
- Targeting senescence to prevent diabetic kidney disease: Exploring molecular mechanisms and potential therapeutic targets for disease management.Diabetic medicine : a journal of the British Diabetic Association · 2025Review
- Sodium glucose transporter 2 inhibitors: Will these drugs benefit non-diabetic veterinary patients with cardiac and kidney diseases?Journal of veterinary pharmacology and therapeutics · 2025Review
- mTORC1 signaling and diabetic kidney disease.Diabetology international · 2024Review
- Expression of Autophagy Markers LC3B, LAMP2A, and GRP78 in the Human Kidney during Embryonic, Early Fetal, and Postnatal Development and Their Significance in Diabetic Kidney Disease.International journal of molecular sciences · 2024Article
- AMPK pathway: an emerging target to control diabetes mellitus and its related complications.Journal of diabetes and metabolic disorders · 2024Review
- Qufeng tongluo decoction decreased proteinuria in diabetic mice by protecting podocytes via promoting autophagy.Journal of traditional and complementary medicine · 2024Article
- The AMPK-Sirtuin 1-YAP axis is regulated by fluid flow intensity and controls autophagy flux in kidney epithelial cells.Nature communications · 2023Article
- Review
- Identification of genetic variants associated with diabetic kidney disease in multiple Korean cohorts via a genome-wide association study mega-analysis.BMC medicine · 2023Article
- The role of autophagy in the treatment of type II diabetes and its complications: a review.Frontiers in endocrinology · 2023Review
- Review
- Hypertriglyceridemia and Other Risk Factors of Chronic Kidney Disease in Type 2 Diabetes: A Hospital-Based Clinic Population in Greece.Journal of clinical medicine · 2022Article
63 more citing papers are in PubMed but not listed here.
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Authors and funding
14 authors at 4 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Obesity is an independent risk factor for renal dysfunction in patients with CKDs, including diabetic nephropathy, but the mechanism underlying this connection remains unclear. Autophagy is an intracellular degradation system that maintains intracellular homeostasis by removing damaged proteins and organelles, and autophagy insufficiency is associated with the pathogenesis of obesity-related diseases. We therefore examined the role of autophagy in obesity-mediated exacerbation of proteinuria-induced proximal tubular epithelial cell damage in mice and in human renal biopsy specimens. In nonobese mice, overt proteinuria, induced by intraperitoneal free fatty acid-albumin overload, led to mild tubular damage and apoptosis, and activated autophagy in proximal tubules reabsorbing urinary albumin. In contrast, diet-induced obesity suppressed proteinuria-induced autophagy and exacerbated proteinuria-induced tubular cell damage. Proximal tubule-specific autophagy-deficient mice, resulting from an Atg5 gene deletion, subjected to intraperitoneal free fatty acid-albumin overload developed severe proteinuria-induced tubular damage, suggesting that proteinuria-induced autophagy is renoprotective. Mammalian target of rapamycin (mTOR), a potent suppressor of autophagy, was activated in proximal tubules of obese mice, and treatment with an mTOR inhibitor ameliorated obesity-mediated autophagy insufficiency. Furthermore, both mTOR hyperactivation and autophagy suppression were observed in tubular cells of specimens obtained from obese patients with proteinuria. Thus, in addition to enhancing the understanding of obesity-related cell vulnerability in the kidneys, these results suggest that restoring the renoprotective action of autophagy in proximal tubules may improve renal outcomes in obese patients.
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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.