The Vicious Cycle of Renal Lipotoxicity and Mitochondrial Dysfunction

Ge, Mengyuan; Fontanesi, Flavia; Merscher, Sandra; Fornoni, Alessia

doi:10.3389/fphys.2020.00732

Cited by 33 publications

(33 citation statements)

References 153 publications

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“… 36 , 37 The evidence presented supported the strong relationship between mitochondrial dysfunction and abundant oxidative stress. 38 In the work, we found the mitochondrial membrane potential loss and calcium overload were obvious in the kidney tissue after CLP procedure, indicating mitochondrial dysfunction occurred in the septic kidney. Not surprisingly, improved mitochondrial function reflected by elevated mitochondrial membrane potential and decreased calcium overload in the septic kidney was concurrently remitted by Loganin.…”

Section: Discussionmentioning

confidence: 78%

Loganin Attenuates Septic Acute Renal Injury with the Participation of AKT and Nrf2/HO-1 Signaling Pathways

Zhang¹,

Wang²,

Kang³

et al. 2021

DDDT

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Purpose: Sepsis, a destructive inflammatory response syndrome, is the principal reason to induce death in the intensive care unit. Loganin has been proved to possess the property of anti-inflammation, antioxidant, neuroprotection, and sedation. The primary aim of this study was to evaluate whether Loganin could alleviate acute kidney injury (AKI) during sepsis and investigate the latent mechanisms. Methods: Septic AKI models were established by cecal ligation and puncture (CLP) surgery in mice and given Loganin (20, 40, 80 mg/kg) by gavage. Lipopolysaccharides (LPS)stimulated human kidney proximal tubular (HK2) cells incubated in Loganin (5, 10, 20 μ M) were used to explore the accurate mechanisms. Survival rate, renal function (creatinine and blood urea nitrogen), and renal pathological changes were detected in septic mice. Oxidative stress markers (SOD, GSH-Px, MDA, and SOD), mitochondrial membrane potential, mitochondrial calcium overload, and nuclear factor E2-related factor 2 (Nrf2)/hemeoxygenase 1 (HO-1) pathway activation in vivo and in vitro were determined by commercial kits and Western blot. Cell apoptosis, apoptotic-related protein (cleaved caspase-3, Bcl-2, and Bax) expression and protein kinase B (AKT) phosphorylation in vivo and in vitro were measured by TUNEL staining and Western blot. Finally, AKT blockage by 10 μM LY294002 or Nrf2 inhibition by10 μ M ML385 were utilized to prove the involvement of AKT and Nrf2/HO-1 pathway in AKI during sepsis. Results: We found Loganin treatment (20, 40, 80 mg/kg) mitigated septic AKI reflected by elevated renal function and palliative pathological changes. Oxidative stress and apoptosis in the kidney and LPS-treated HK2 cells were also inhibited by Loganin administration, which was accompanied by AKT and Nrf2/HO-1 pathway activation. Besides, the protective effects of Loganin could be diminished by AKT or Nrf2 blockage, indicating the involvement of AKT and Nrf2/HO-1 pathway. Conclusion: The results suggested that the protective effects of Loganin on AKI during sepsis might be mediated by AKT and Nrf2/HO-1 pathway signaling activation in kidney proximal tubular cells.

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Section: Discussionmentioning

confidence: 78%

Loganin Attenuates Septic Acute Renal Injury with the Participation of AKT and Nrf2/HO-1 Signaling Pathways

Zhang¹,

Wang²,

Kang³

et al. 2021

DDDT

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“…In kidney diseases, the uptake of lipids by CD36, along with the dysfunction of FA β-oxidation, causes lipids accumulation in lipid droplets (LDs), inducing ROS overproduction (Figure 4) [129,130]. Since ROS and their products induce severe cell damage, a cellular balance of ROS is needed.…”

Section: Oxidation and Os Production And In Kidney Diseasesmentioning

confidence: 99%

Mitochondrial Redox Signaling and Oxidative Stress in Kidney Diseases

et al. 2021

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Mitochondria are essential organelles in physiology and kidney diseases, because they produce cellular energy required to perform their function. During mitochondrial metabolism, reactive oxygen species (ROS) are produced. ROS function as secondary messengers, inducing redox-sensitive post-translational modifications (PTM) in proteins and activating or deactivating different cell signaling pathways. However, in kidney diseases, ROS overproduction causes oxidative stress (OS), inducing mitochondrial dysfunction and altering its metabolism and dynamics. The latter processes are closely related to changes in the cell redox-sensitive signaling pathways, causing inflammation and apoptosis cell death. Although mitochondrial metabolism, ROS production, and OS have been studied in kidney diseases, the role of redox signaling pathways in mitochondria has not been addressed. This review focuses on altering the metabolism and dynamics of mitochondria through the dysregulation of redox-sensitive signaling pathways in kidney diseases.

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“…Disturbed mitochondrial fatty acid oxidation causes energetic failure of proximal tubules [ 61 ]. Furthermore, mitochondrial dysfunction results in decreased lipid oxidation followed by lipid accumulation, which leads to a vicious cycle of mitochondrial dysfunction and lipotoxicity [ 62 ].…”

Section: Mechanisms Underlying the Renoprotective Effect Of Sglt2 Inhibitorsmentioning

confidence: 99%

Pleiotropic Effects of Sodium-Glucose Cotransporter-2 Inhibitors: Renoprotective Mechanisms beyond Glycemic Control

Takata

Isomoto

2021

IJMS

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Diabetes mellitus is a major cause of chronic kidney disease and end-stage renal disease. However, the management of chronic kidney disease, particularly diabetes, requires vast improvements. Recently, sodium-glucose cotransporter-2 (SGLT2) inhibitors, originally developed for the treatment of diabetes, have been shown to protect against kidney injury via glycemic control, as well as various other mechanisms, including blood pressure and hemodynamic regulation, protection from lipotoxicity, and uric acid control. As such, regulation of these mechanisms is recommended as an effective multidisciplinary approach for the treatment of diabetic patients with kidney disease. Thus, SGLT2 inhibitors are expected to become key drugs for treating diabetic kidney disease. This review summarizes the recent clinical evidence pertaining to SGLT2 inhibitors as well as the mechanisms underlying their renoprotective effects. Hence, the information contained herein will advance the current understanding regarding the pleiotropic effects of SGLT2 inhibitors, while promoting future research in the field.

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The Vicious Cycle of Renal Lipotoxicity and Mitochondrial Dysfunction

Cited by 33 publications

References 153 publications

Loganin Attenuates Septic Acute Renal Injury with the Participation of AKT and Nrf2/HO-1 Signaling Pathways

Loganin Attenuates Septic Acute Renal Injury with the Participation of AKT and Nrf2/HO-1 Signaling Pathways

Mitochondrial Redox Signaling and Oxidative Stress in Kidney Diseases

Pleiotropic Effects of Sodium-Glucose Cotransporter-2 Inhibitors: Renoprotective Mechanisms beyond Glycemic Control

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