ArticleThe Journal of biological chemistry2016
Farnesoid X Receptor Protects against Kidney Injury in Uninephrectomized Obese Mice.
Article in The Journal of biological chemistry, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 47 papers.
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47 citing papers in PubMed, 93 citations in OpenAlex.
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- Pharmacological Activation of FXR Attenuates Renal Fibrosis and Pyroptosis-Associated Signaling in Aldosterone-Infused Mice.Journal of inflammation research · 2026Article
- DHLCA Alleviates Diabetic Kidney Disease via TGR5/FXR Activation and Gut Microbiota Remodeling.Drug design, development and therapy · 2025Article
- Proteomic profiling of serum in cats with naturally occurring degenerative joint disease and co-morbid conditions.Frontiers in pain research (Lausanne, Switzerland) · 2025Article
- Chenodeoxycholic acid alleviated the cyclosporine-induced nephrotoxicity by decreasing oxidative stress and suppressing renin-angiotensin system through AT2R and ACE2 mRNA upregulation in rats.Journal of molecular histology · 2024Article
- Obeticholic acid ameliorates sepsis-induced renal mitochondrial damage by inhibiting the NF-κb signaling pathway.Renal failure · 2024Article
- Role of Bile Acid Receptors in the Development and Function of Diabetic Nephropathy.Kidney international reports · 2024Review
- Cardiometabolic comorbidities and complications of obesity and chronic kidney disease (CKD).Journal of clinical & translational endocrinology · 2024Review
- Lipids: A Major Culprit in Diabetic Nephropathy.Current diabetes reviews · 2024Review
- Gut microbiota and bile acids: Metabolic interactions and impacts on diabetic kidney disease.Current research in microbial sciences · 2024Review
- Farnesoid X receptor prevents neutrophil extracellular traps via reduced sphingosine-1-phosphate in chronic kidney disease.American journal of physiology. Renal physiology · 2023Article
- Emerging significance and therapeutic targets of ferroptosis: a potential avenue for human kidney diseases.Cell death & disease · 2023Review
- Role of FXR in Renal Physiology and Kidney Diseases.International journal of molecular sciences · 2023Review
- Loss of Farnesoid X receptor (FXR) accelerates dysregulated glucose and renal injury in db/db mice.PeerJ · 2023Article
- Peroxisome proliferator-activated receptors, farnesoid X receptor, and dual modulating drugs in hypertension.Frontiers in physiology · 2023Review
- The Farnesoid X Receptor as a Master Regulator of Hepatotoxicity.International journal of molecular sciences · 2022Review
- Farnesoid X receptor protects against cisplatin-induced acute kidney injury by regulating the transcription of ferroptosis-related genes.Redox biology · 2022Article
- Effects of Sporisorium reiliana polysaccharides and Phoenix dactylifera monosaccharides on the gut microbiota and serum metabolism in mice with fructose-induced hyperuricemia.Archives of microbiology · 2022Article
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Authors and funding
4 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Activation of the farnesoid X receptor (FXR) has indicated a therapeutic potential for this nuclear bile acid receptor in the prevention of diabetic nephropathy and obesity-induced renal damage. Here, we investigated the protective role of FXR against kidney damage induced by obesity in mice that had undergone uninephrectomy, a model resembling the clinical situation of kidney donation by obese individuals. Mice fed a high-fat diet developed the core features of metabolic syndrome, with subsequent renal lipid accumulation and renal injury, including glomerulosclerosis, interstitial fibrosis, and albuminuria. The effects were accentuated by uninephrectomy. In human renal biopsies, staining of 4-hydroxynonenal (4-HNE), glucose-regulated protein 78 (Grp78), and C/EBP-homologous protein, markers of endoplasmic reticulum stress, was more prominent in the proximal tubules of 15 obese patients compared with 16 non-obese patients. In mice treated with the FXR agonist obeticholic acid, renal injury, renal lipid accumulation, apoptosis, and changes in lipid peroxidation were attenuated. Moreover, disturbed mitochondrial function was ameliorated and the mitochondrial respiratory chain recovered following obeticholic acid treatment. Culturing renal proximal tubular cells with free fatty acid and FXR agonists showed that FXR activation protected cells from free fatty acid-induced oxidative stress and endoplasmic reticulum stress, as denoted by a reduction in the level of reactive oxygen species staining and Grp78 immunostaining, respectively. Several genes involved in glutathione metabolism were induced by FXR activation in the remnant kidney, which was consistent with a decreased glutathione disulfide/glutathione ratio. In summary, FXR activation maintains endogenous glutathione homeostasis and protects the kidney in uninephrectomized mice from obesity-induced injury.
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