scholarly journals GLP-1 receptor agonist ameliorates obesity-induced chronic kidney injury via restoring renal lipid and energy metabolism homeostasis: revealed by metabolomics

2017 ◽  
Author(s):  
Chengshi Wang ◽  
Ling Li ◽  
Shuyun Liu ◽  
Guangneng Liao ◽  
Younan Chen ◽  
...  
Keyword(s):  
Renal Function ◽  
Energy Metabolism ◽  
High Fat Diet ◽  
Receptor Agonist ◽  
Kidney Diseases ◽  
Kidney Injury ◽  
Direct Role ◽  
Chronic Kidney Injury ◽  
Metabolomic Data

AbstractIncreasing evidence indicate that obesity is highly associated with chronic kidney disease (CKD).GLP-1 receptor (GLP-1R) agonist has shown benefits on kidney diseases, but its direct role on kidney metabolism in obesity is still not clear. This study aims to investigate the protection and metabolic modulation role of liraglutide (Lira) on kidney of obesity. Rats were induced obese by high-fat diet (HFD), and renal function and metabolism changes were evaluated by metabolomic, biological and histological methods. HFD rats exhibited metabolic disorders including elevated body weight, hyperlipidemia and impaired glucose tolerance, and remarkable renal injuries including declined renal function and inflammatory/fibrotic changes, whereas Lira significantly ameliorated these adverse effects in HFD rats. Metabolomic data showed that Lira reduced renal lipids including fatty acid residues, cholesterol, phospholipids and triglycerides, and improved mitochondria metabolites such as succinate, citrate, taurine, fumarate and NAD+ in the kidney of HDF rats. Furthermore, we revealed that Lira inhibited renal lipid accumulation by coordinating lipogenic and lipolytic signals, and rescued renal mitochondria function via Sirt1/AMPK/PGC1α pathways in HDF rats. This study suggested that Lira alleviated HFD-induced kidney injury via directly restoring renal lipid and energy metabolism, and GLP-1 receptor agonist is a promising therapy for obesity-associated CKD.

scholarly journals Stem cells: potential and challenges for kidney repair

2014 ◽  
Vol 306 (1) ◽  
pp. F12-F23 ◽  
Author(s):  
Marcela Herrera ◽  
Maria Mirotsou
Keyword(s):  
Stem Cells ◽  
Renal Damage ◽  
Kidney Diseases ◽  
Kidney Injury ◽  
Pathological Conditions ◽  
Emerging Therapies ◽  
Chronic Kidney Injury ◽  
Stage Renal Disease ◽  
End Stage

Renal damage resulting from acute and chronic kidney injury poses an important problem to public health. Currently, patients with end-stage renal disease rely solely on kidney transplantation or dialysis for survival. Emerging therapies aiming to prevent and reverse kidney damage are thus in urgent need. Although the kidney was initially thought to lack the capacity for self-repair, several studies have indicated that this might not be the case; progenitor and stem cells appear to play important roles in kidney repair under various pathological conditions. In this review, we summarize recent findings on the role of progenitor/stem cells on kidney repair as well as discuss their potential as a therapeutic approach for kidney diseases.

scholarly journals The Role of PGC-1α and Mitochondrial Biogenesis in Kidney Diseases

Biomolecules ◽  
2020 ◽  
Vol 10 (2) ◽  
pp. 347 ◽  
Author(s):  
Miguel Fontecha-Barriuso ◽  
Diego Martin-Sanchez ◽  
Julio Manuel Martinez-Moreno ◽  
Maria Monsalve ◽  
Adrian Mario Ramos ◽  
...  
Keyword(s):  
Mitochondrial Biogenesis ◽  
Kidney Diseases ◽  
Ischemia Reperfusion ◽  
Kidney Injury ◽  
Pde Inhibitors ◽  
Its Gene ◽  
Attractive Therapeutic Target ◽  
Amp Activated Protein Kinase

Chronic kidney disease (CKD) is one of the fastest growing causes of death worldwide, emphasizing the need to develop novel therapeutic approaches. CKD predisposes to acute kidney injury (AKI) and AKI favors CKD progression. Mitochondrial derangements are common features of both AKI and CKD and mitochondria-targeting therapies are under study as nephroprotective agents. PGC-1α is a master regulator of mitochondrial biogenesis and an attractive therapeutic target. Low PGC-1α levels and decreased transcription of its gene targets have been observed in both preclinical AKI (nephrotoxic, endotoxemia, and ischemia-reperfusion) and in experimental and human CKD, most notably diabetic nephropathy. In mice, PGC-1α deficiency was associated with subclinical CKD and predisposition to AKI while PGC-1α overexpression in tubular cells protected from AKI of diverse causes. Several therapeutic strategies may increase kidney PGC-1α activity and have been successfully tested in animal models. These include AMP-activated protein kinase (AMPK) activators, phosphodiesterase (PDE) inhibitors, and anti-TWEAK antibodies. In conclusion, low PGC-1α activity appears to be a common feature of AKI and CKD and recent characterization of nephroprotective approaches that increase PGC-1α activity may pave the way for nephroprotective strategies potentially effective in both AKI and CKD.

Mitochondrial dysfunction and the AKI-to-CKD transition

2020 ◽  
Vol 319 (6) ◽  
pp. F1105-F1116
Author(s):  
Mingzhu Jiang ◽  
Mi Bai ◽  
Juan Lei ◽  
Yifan Xie ◽  
Shuang Xu ◽  
...  
Keyword(s):  
Therapeutic Strategy ◽  
Kidney Diseases ◽  
Kidney Injury ◽  
Mitochondrial Homeostasis ◽  
Cycle Arrest ◽  
Persistent Inflammation ◽  
Acute Injuries ◽  
Nephron Loss ◽  
Effective Therapeutic Strategy

Acute kidney injury (AKI) has been widely recognized as an important risk factor for the occurrence and development of chronic kidney disease (CKD). Even milder AKI has adverse consequences and could progress to renal fibrosis, which is the ultimate common pathway for various terminal kidney diseases. Thus, it is urgent to develop a strategy to hinder the transition from AKI to CKD. Some mechanisms of the AKI-to-CKD transition have been revealed, such as nephron loss, cell cycle arrest, persistent inflammation, endothelial injury with vascular rarefaction, and epigenetic changes. Previous studies have elucidated the pivotal role of mitochondria in acute injuries and demonstrated that the fitness of this organelle is a major determinant in both the pathogenesis and recovery of organ function. Recent research has suggested that damage to mitochondrial function in early AKI is a crucial factor leading to tubular injury and persistent renal insufficiency. Dysregulation of mitochondrial homeostasis, alterations in bioenergetics, and organelle stress cross talk contribute to the AKI-to-CKD transition. In this review, we focus on the pathophysiology of mitochondria in renal recovery after AKI and progression to CKD, confirming that targeting mitochondria represents a potentially effective therapeutic strategy for the progression of AKI to CKD.

scholarly journals The Role of Sirtuins in Kidney Diseases

2020 ◽  
Vol 21 (18) ◽  
pp. 6686
Author(s):  
Yu Ah Hong ◽  
Ji Eun Kim ◽  
Minjee Jo ◽  
Gang-Jee Ko
Keyword(s):  
Histone Deacetylases ◽  
Energy Homeostasis ◽  
Molecular Mechanisms ◽  
Kidney Diseases ◽  
Expression Profiles ◽  
Kidney Injury ◽  
Class Iii ◽  
Cellular Functions ◽  
Wide Range

Sirtuins (SIRTs) are class III histone deacetylases (HDACs) that play important roles in aging and a wide range of cellular functions. Sirtuins are crucial to numerous biological processes, including proliferation, DNA repair, mitochondrial energy homeostasis, and antioxidant activity. Mammals have seven different sirtuins, SIRT1–7, and the diverse biological functions of each sirtuin are due to differences in subcellular localization, expression profiles, and cellular substrates. In this review, we summarize research advances into the role of sirtuins in the pathogenesis of various kidney diseases including acute kidney injury, diabetic kidney disease, renal fibrosis, and kidney aging along with the possible underlying molecular mechanisms. The available evidence indicates that sirtuins have great potential as novel therapeutic targets for the prevention and treatment of kidney diseases.

Decreased Renal Function Induced by High-Fat Diet in Wistar Rat: The Role of Plasma Angiotensin Converting Enzyme 2 (ACE2)

2019 ◽  
Vol 12 (3) ◽  
pp. 1279-1287
Author(s):  
Ridwan Ridwan ◽  
Rosdiana Natzir ◽  
Haerani Rasyid ◽  
Ilhamjaya Patellongi ◽  
Mochammad Hatta ◽  
...  
Keyword(s):  
Renal Function ◽  
Body Weight ◽  
Body Fat ◽  
High Fat Diet ◽  
Early Stage ◽  
Body Fat Percentage ◽  
Fat Percentage ◽  
Angiotensin Converting Enzyme 2 ◽  
Obesity Index

Researches on the effects of High Fat Diet (HFD) on decreased renal function with cystatin C (cysC) serum levels biomarker are few and show different findings. Renin Angiotensin System (RAS) plays a key role in controlling renal function and one of the integral components of the RAS is Angiotensin Converting Enzyme 2 (ACE2). Research on the relationship between plasma ACE2 levels with serum cysC levels in animals induced by HFD has not been done. We hypothesize that administration of HFD can cause a decline in early stage renal function through the role of ACE2. 30 male wistar rats aged 10-12 weeks (body weight between 170-220 grams) were randomly divided into 5 groups (6 rats/group): baseline, normal diet for 8 weeks (ND8), ND for 16 weeks (ND16), HFD for 8 weeks (HFD8) and HFD for 16 weeks (HFD16). Body weight and naso-anal length were measured to get the index value of obesity and body fat percentage. Obesity index measured are lee index, rohrer index and TM index. Blood samples obtained by intracardiac for examination of plasma ACE2 levels and serum cysC levels. After 8 and 16 weeks, HFD increases body weight, obesity index and body fat percentage. HFD also increases plasma ACE2 levels and serum cysC levels. Body weight, obesity index and body fat percentage have a positive correlation with plasma ACE2 levels. Plasma ACE2 levels were positively correlated with serum cysC levels. HFD causes a decrease of early stage renal function as evidenced by the increase in serum cysC levels. Plasma ACE2 levels play a role in the pathogenesis of the decline in early stage renal function induced by HFD.

scholarly journals Delayed treatment with fenofibrate protects against high-fat diet-induced kidney injury in mice: the possible role of AMPK autophagy

2017 ◽  
Vol 312 (2) ◽  
pp. F323-F334 ◽  
Author(s):  
Minji Sohn ◽  
Keumji Kim ◽  
Md Jamal Uddin ◽  
Gayoung Lee ◽  
Inah Hwang ◽  
...  
Keyword(s):  
High Fat Diet ◽  
Kidney Injury ◽  
Acid Oxidation ◽  
Peroxisome Proliferator ◽  
Dependent Manner ◽  
High Fat ◽  
Concentration Dependent Manner ◽  
Delayed Treatment ◽  
Compound C

Fenofibrate activates not only peroxisome proliferator-activated receptor-α (PPARα) but also adenosine monophosphate-activated protein kinase (AMPK). AMPK-mediated cellular responses protect kidney from high-fat diet (HFD)-induced injury, and autophagy resulting from AMPK activation has been regarded as a stress-response mechanism. Thus the present study examined the role of AMPK and autophagy in the renotherapeutic effects of fenofibrate. C57BL/6J mice were divided into three groups: normal diet (ND), HFD, and HFD + fenofibrate (HFD + FF). Fenofibrate was administered 4 wk after the initiation of the HFD when renal injury was initiated. Mouse proximal tubule cells (mProx24) were used to clarify the role of AMPK. Feeding mice with HFD for 12 wk induced insulin resistance and kidney injury such as albuminuria, glomerulosclerosis, tubular injury, and inflammation, which were effectively inhibited by fenofibrate. In addition, fenofibrate treatment resulted in the activation of renal AMPK, upregulation of fatty acid oxidation (FAO) enzymes and antioxidants, and induction of autophagy in the HFD mice. In mProx24 cells, fenofibrate activated AMPK in a concentration-dependent manner, upregulated FAO enzymes and antioxidants, and induced autophagy, all of which were inhibited by treatment of compound C, an AMPK inhibitor. Fenofibrate-induced autophagy was also significantly blocked by AMPKα1 siRNA but not by PPARα siRNA. Collectively, these results demonstrate that delayed treatment with fenofibrate has a therapeutic effect on HFD-induced kidney injury, at least in part, through the activation of AMPK and induction of subsequent downstream effectors: autophagy, FAO enzymes, and antioxidants.

scholarly journals Tissue Kidney Injury Molecule-1 Expression in the Prediction of Renal Function for Several Years after Kidney Biopsy

2013 ◽  
Vol 35 ◽  
pp. 567-572 ◽  
Author(s):  
Sanja Simic Ogrizovic ◽  
Suzana Bojic ◽  
Gordana Basta-Jovanovic ◽  
Sanja Radojevic ◽  
Jelena Pavlovic ◽  
...  
Keyword(s):  
Renal Function ◽  
Retrospective Study ◽  
Kidney Function ◽  
Kidney Biopsy ◽  
Kidney Diseases ◽  
Kidney Injury ◽  
Mdrd Formula ◽  
Positive Correlations ◽  
Kidney Injury Molecule 1 ◽  
Kidney Functions

Objectives. Retrospective study was designed to examine the importance of tissue kidney injury molecule-1 (KIM-1) expression in predicting kidney function in sixty patients (27 males) aged 34.15 ± 12.23 years with different kidney diseases over three years after kidney biopsy.Materials and Methods. Tissue KIM-1 expression was determined immunohistochemically and KIM-1 staining was scored semiquantitatively, as well as tubulointerstitialis (TIN), inflammation, atrophy, and fibrosis. Kidney function (MDRD formula) and proteinuria/day were evaluated at the time of biopsy (GFR0) and 6, 12, 24, and 36 months later.Results. Significantly positive correlations between tissue KIM-1 expression and age (r=0.313), TIN inflammation (r=0.456), fibrosis (r=0.317), and proteinuria at 6 months (r=0.394) as well as negative correlations with GFR0 (r=−0.572), GFR6 (r=−0.442), GFR24 (r=−0.398), and GFR36 (r=−0.412) were found. Meanwhile, TIN inflammation was the best predictor of all measured kidney functions during three years, while tissue KIM-1 expression (P=0.016) was a predictor only at 6 months after biopsy.Conclusion. Tissue KIM-1 expression significantly predicts kidney function solely at 6 months after biopsy, when the effects of immune and nonimmune treatments are the strongest.

scholarly journals Use of Lipid-Modifying Agents for the Treatment of Glomerular Diseases

2021 ◽  
Vol 11 (8) ◽  
pp. 820
Author(s):  
Mengyuan Ge ◽  
Sandra Merscher ◽  
Alessia Fornoni
Keyword(s):  
Chronic Kidney Disease ◽  
Kidney Disease ◽  
Recent Progress ◽  
Kidney Diseases ◽  
Kidney Injury ◽  
Glomerular Diseases ◽  
Intracellular Lipids ◽  
Lipid Modifying Agents ◽  
Made In

Although dyslipidemia is associated with chronic kidney disease (CKD), it is more common in nephrotic syndrome (NS), and guidelines for the management of hyperlipidemia in NS are largely opinion-based. In addition to the role of circulating lipids, an increasing number of studies suggest that intrarenal lipids contribute to the progression of glomerular diseases, indicating that proteinuric kidney diseases may be a form of “fatty kidney disease” and that reducing intracellular lipids could represent a new therapeutic approach to slow the progression of CKD. In this review, we summarize recent progress made in the utilization of lipid-modifying agents to lower renal parenchymal lipid accumulation and to prevent or reduce kidney injury. The agents mentioned in this review are categorized according to their specific targets, but they may also regulate other lipid-relevant pathways.

Sign in / Sign up

Export Citation Format

Share Document