Kidney lipid dysmetabolism and lipid droplet accumulation in chronic kidney disease

Mitrofanova, Alla; Merscher, Sandra; Fornoni, Alessia

doi:10.1038/s41581-023-00741-w

Cited by 67 publications

(30 citation statements)

References 263 publications

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“…Additionally, cisplatin-induced AKI is known to impair mitochondrial fatty acid β-oxidation, resulting in ectopic lipid accumulation. 54,55 Mice treated with Cur showed less damage to the mitochondria and fewer lipid droplets. In comparison, samples from NPS BG @Cur-treated AKI mice showed abundant normally structured mitochondria with distinct cristae architecture.…”

Section: Resultsmentioning

confidence: 96%

ROS-responsive curcumin-encapsulated nanoparticles for AKI therapy via promoting lipid degradation in renal tubules

Guo,

Lan,

et al. 2024

J. Mater. Chem. B

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Section: Resultsmentioning

confidence: 96%

ROS-responsive curcumin-encapsulated nanoparticles for AKI therapy via promoting lipid degradation in renal tubules

Guo,

Lan,

et al. 2024

J. Mater. Chem. B

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“…They are at a high baseline level of energy consumption. Fatty acid oxidation (FAO) is a primary source to meet their energy demands 27,28 . The regulation of lipid metabolism and FAO heavily depends on the activation of peroxisome proliferator–activated receptor α (PPARα) 29 .…”

Section: Introductionmentioning

confidence: 99%

C‐X‐C chemokine receptor type 4 promotes tubular cell senescence and renal fibrosis through β‐catenin‐inhibited fatty acid oxidation

Wu,

Chen,

et al. 2024

J Cellular Molecular Medi

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The prevalence of chronic kidney disease (CKD) is highly increasing. Renal fibrosis is a common pathological feature in various CKD. Previous studies showed tubular cell senescence is highly involved in the pathogenesis of renal fibrosis. However, the inducers of tubular senescence and the underlying mechanisms have not been fully investigated. C‐X‐C motif chemokine receptor 4 (CXCR4), a G‐protein‐coupled seven‐span transmembrane receptor, increases renal fibrosis and plays an important role in tubular cell injury. Whereas, whether CXCR4 could induce tubular cell senescence and the detailed mechanisms have not studied yet. In this study, we adopted adriamycin nephropathy and 5/6 nephrectomy models, and cultured tubular cell line. Overexpression or knockdown of CXCR4 was obtained by injection of related plasmids. We identified CXCR4 increased in injury tubular cells. CXCR4 was expressed predominantly in renal tubular epithelial cells and co‐localized with adipose differentiation‐related protein (ADRP) as well as the senescence‐related protein P16INK4A. Furthermore, we found overexpression of CXCR4 greatly induced the activation of β‐catenin, while knockdown of CXCR4 inhibited it. We also found that CXCR4 inhibited fatty acid oxidation and triggered lipid deposition in tubular cells. To inhibit β‐catenin by ICG‐001, an inhibitor of β‐catenin, could significantly block CXCR4‐suppressed fatty acid oxidation. Taken together, our results indicate that CXCR4 is a key mediator in tubular cell senescence and renal fibrosis. CXCR4 promotes tubular cell senescence and renal fibrosis by inducing β‐catenin and inhibiting fatty acid metabolism. Our findings provide a new theory for tubular cell injury in renal fibrosis.

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“…Multiple stressors predispose individuals to CKD today, including diabetes, obesity, and hyperuricemia. 3 Significantly, it is dyslipidemia, a common factor among these triggers, that has been identified as a critical driver of CKD progression and its complications, such as renal atherosclerosis, 4,5 as evidenced by both human and animal studies. 6,7 Upon chronic hyperlipidemia, renal lipotoxicity could arise gradually with excess lipid archiving in the kidneys, which, in turn, provokes mitochondrial dysfunction, oxidative stress, and inflammatory responses.…”

Section: Introductionmentioning

confidence: 99%

Magnoflorine Ameliorates Chronic Kidney Disease in High-Fat and High-Fructose-Fed Mice by Promoting Parkin/PINK1-Dependent Mitophagy to Inhibit NLRP3/Caspase-1-Mediated Pyroptosis

Cheng,

Lu,

Mao

et al. 2024

J. Agric. Food Chem.

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Excessive intake of fat and fructose in Western diets has been confirmed to induce renal lipotoxicity, thereby driving the progression of chronic kidney disease (CKD). This study was conducted to evaluate the efficacy of magnoflorine in a CKD mouse model subjected to high-fat and high-fructose diets. Our results demonstrated that magnoflorine treatment ameliorated abnormal renal function indices (serum creatinine, urea nitrogen, uric acid, and urine protein) in high-fat- and high-fructose-fed mice. Histologically, renal tubular cell steatosis, lipid deposition, tubular dilatation, and glomerular fibrosis were significantly reduced by the magnoflorine treatment in these mice. Mechanistically, magnoflorine promotes Parkin/PINK1-mediated mitophagy, thereby inhibiting NLRP3/Caspase-1-mediated pyroptosis. Consistent findings were observed in the palmitic acid-incubated HK-2 cell model. Notably, both silencing of Parkin and the use of a mitophagy inhibitor reversed the inhibitory effect of magnoflorine on NLRP3 inflammasome activation in vitro. Therefore, the present study provides compelling evidence that magnoflorine improves renal injury in high-fat- and high-fructose-fed mice by promoting Parkin/PINK1-dependent mitophagy to inhibit NLRP3 inflammasome activation and pyroptosis. Our findings suggest that dietary supplementation with magnoflorine and magnoflorine-rich foods (such as magnolia) might be an effective strategy for the prevention of CKD.

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Kidney lipid dysmetabolism and lipid droplet accumulation in chronic kidney disease

Cited by 67 publications

References 263 publications

ROS-responsive curcumin-encapsulated nanoparticles for AKI therapy via promoting lipid degradation in renal tubules

ROS-responsive curcumin-encapsulated nanoparticles for AKI therapy via promoting lipid degradation in renal tubules

C‐X‐C chemokine receptor type 4 promotes tubular cell senescence and renal fibrosis through β‐catenin‐inhibited fatty acid oxidation

Magnoflorine Ameliorates Chronic Kidney Disease in High-Fat and High-Fructose-Fed Mice by Promoting Parkin/PINK1-Dependent Mitophagy to Inhibit NLRP3/Caspase-1-Mediated Pyroptosis

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