The attenuation of diabetic nephropathy by annexin A1 via regulation of lipid metabolism through AMPK/PPARα/CPT1b pathway

Diabetes ◽  
2021 ◽  
pp. db210050
Author(s):  
Liang Wu ◽  
Changjie Liu ◽  
Dong-Yuan Chang ◽  
Rui Zhan ◽  
Mingming Zhao ◽  
...  
2021 ◽  
Author(s):  
Liang Wu ◽  
Changjie Liu ◽  
Dong-Yuan Chang ◽  
Rui Zhan ◽  
Mingming Zhao ◽  
...  

Inflammation and abnormal metabolism play important roles in the pathogenesis of diabetic nephropathy (DN). Annexin A1 (ANXA1) contributes to inflammation resolution and improves metabolism. Here, we assess the effects of ANXA1 in diabetic mice and proximal tubular epithelial cells (PTECs) treated with high glucose plus palmitate acid (HGPA), and explore the association of ANXA1 with lipid accumulation in DN patients. It is found that ANXA1 deletion aggravates renal injuries, including albuminuria, mesangial matrix expansion and tubulointerstitial lesions in HFD/STZ-induced diabetic mice. ANXA1 deficiency promotes intra-renal lipid accumulation and drives mitochondrial alterations in kidneys. In addition, Ac2-26, an ANXA1 mimetic peptide, has a therapeutic effect against lipid toxicity in diabetic mice. In HGPA-treated human PTECs, <i>ANXA1</i> silencing causes FPR2/ALX-driven deleterious effects, which suppress phosphorylated Thr<sup>172</sup>AMPK, resulting in decreased PPARα and CPT1b expression and increased HGPA-induced lipid accumulation, apoptosis and elevated expression of pro-inflammatory and pro-fibrotic genes. Last but not least, the extent of lipid accumulation correlates with renal function, and the level of tubulointerstitial ANXA1 expression correlates with ectopic lipid deposition in kidneys of DN patients. These data demonstrate that ANXA1 regulates lipid metabolism of PTECs to ameliorate disease progression, hence it holds great potential as a therapeutic target for DN.


2021 ◽  
Author(s):  
Liang Wu ◽  
Changjie Liu ◽  
Dong-Yuan Chang ◽  
Rui Zhan ◽  
Mingming Zhao ◽  
...  

Inflammation and abnormal metabolism play important roles in the pathogenesis of diabetic nephropathy (DN). Annexin A1 (ANXA1) contributes to inflammation resolution and improves metabolism. Here, we assess the effects of ANXA1 in diabetic mice and proximal tubular epithelial cells (PTECs) treated with high glucose plus palmitate acid (HGPA), and explore the association of ANXA1 with lipid accumulation in DN patients. It is found that ANXA1 deletion aggravates renal injuries, including albuminuria, mesangial matrix expansion and tubulointerstitial lesions in HFD/STZ-induced diabetic mice. ANXA1 deficiency promotes intra-renal lipid accumulation and drives mitochondrial alterations in kidneys. In addition, Ac2-26, an ANXA1 mimetic peptide, has a therapeutic effect against lipid toxicity in diabetic mice. In HGPA-treated human PTECs, <i>ANXA1</i> silencing causes FPR2/ALX-driven deleterious effects, which suppress phosphorylated Thr<sup>172</sup>AMPK, resulting in decreased PPARα and CPT1b expression and increased HGPA-induced lipid accumulation, apoptosis and elevated expression of pro-inflammatory and pro-fibrotic genes. Last but not least, the extent of lipid accumulation correlates with renal function, and the level of tubulointerstitial ANXA1 expression correlates with ectopic lipid deposition in kidneys of DN patients. These data demonstrate that ANXA1 regulates lipid metabolism of PTECs to ameliorate disease progression, hence it holds great potential as a therapeutic target for DN.


2021 ◽  
Author(s):  
Liang Wu ◽  
Changjie Liu ◽  
Dong-Yuan Chang ◽  
Rui Zhan ◽  
Mingming Zhao ◽  
...  

Inflammation and abnormal metabolism play important roles in the pathogenesis of diabetic nephropathy (DN). Annexin A1 (ANXA1) contributes to inflammation resolution and improves metabolism. Here, we assess the effects of ANXA1 in diabetic mice and proximal tubular epithelial cells (PTECs) treated with high glucose plus palmitate acid (HGPA), and explore the association of ANXA1 with lipid accumulation in DN patients. It is found that ANXA1 deletion aggravates renal injuries, including albuminuria, mesangial matrix expansion and tubulointerstitial lesions in HFD/STZ-induced diabetic mice. ANXA1 deficiency promotes intra-renal lipid accumulation and drives mitochondrial alterations in kidneys. In addition, Ac2-26, an ANXA1 mimetic peptide, has a therapeutic effect against lipid toxicity in diabetic mice. In HGPA-treated human PTECs, <i>ANXA1</i> silencing causes FPR2/ALX-driven deleterious effects, which suppress phosphorylated Thr<sup>172</sup>AMPK, resulting in decreased PPARα and CPT1b expression and increased HGPA-induced lipid accumulation, apoptosis and elevated expression of pro-inflammatory and pro-fibrotic genes. Last but not least, the extent of lipid accumulation correlates with renal function, and the level of tubulointerstitial ANXA1 expression correlates with ectopic lipid deposition in kidneys of DN patients. These data demonstrate that ANXA1 regulates lipid metabolism of PTECs to ameliorate disease progression, hence it holds great potential as a therapeutic target for DN.


2020 ◽  
Vol 236 (1) ◽  
pp. 625-640
Author(s):  
Nan Chen ◽  
Lin Mu ◽  
Zhifen Yang ◽  
Chunyang Du ◽  
Ming Wu ◽  
...  

2014 ◽  
Vol 13 (5) ◽  
pp. 87-92
Author(s):  
Yu. G. Samoilova ◽  
Ye. V. Yurchenko

Was investigated 67 children (36 boys and 31 girls) in age from 6 to 18 years old, with type 1 diabetes patients who were treated at the Children's Hospital Endocrinology number 1 inTomsk, average age of the boys at the time of the survey amounted to (13.0 ± 0.4) years, girls – (13.5 ± 0.4) years. All children diagnosed with type 1 diabetes were under subcompensation. Clinical evaluation of patients included a medical history, physical examination, evaluation of physical development. A study of lipid profile (high-density lipoprotein (HDL) cholesterol, low-density lipoprotein (LDL), cholesterol (TC), triglycerides (TG), atherogenic index). Screening for diabetic retinopathy was performed by examining the fundus by direct ophthalmoscopy after pupil dilation. Diagnosis of diabetic nephropathy, retinopathy performed according to the classification. Patients were divided into groups depending on the presence of complications, and the level of compensation lipid metabolism (children with satisfactory compensation of lipid metabolism (total cholesterol level less than 5.2 mmol / l), children with poor compensation lipid metabolism (total cholesterol above 5.2 mmol / l)). Nature of the subjects studied nutrition using  a questionnaire drawn up on the basis of the standard dietary questionnaire program CINDI, allowing to evaluate the eating habits by examining the frequency of intake of various foods, food preferences and priorities. Products, according to the lipid-lowering diet on the recommendations of the European Society for atherosclerosis were combined and divided into groups according to frequency of use: commonly used products, and rarely use the products. Mathematical treatment of the results was performed using the software package Statistica 5.5 for Windows. In the first phase expected to total group performance statistics – the arithmetic mean value M and the error of the mean m, as well as visualization of the distribution of values was performed using frequency histograms. To select a criterion to assess the significance of paired differences check compliance form normal distribution using the criterion χ2, and also controlled the general equality of variances using the F-test Fisher. Given that these conditions are satisfied only part of the empirical distributions of features tested the hypothesis that the general average in all cases was performed using Mann–Whitney U-test for independent variables. Null hypothesis was rejected when p < 0.05.In the study of lipid metabolism in patients with type 1 diabetes, no increase in the level of cholesterol, triglycerides, HDL, LDL and VLDL – cholesterol in patients with a combination of diabetic nephropathy and retinopathy compared with patients with type 1 diabetes without diabetic microangiopathy. Investigation of the nature of power in patients with type 1 diabetes, allowed us to estimate its impact on lipid metabolism.


2012 ◽  
Vol 9 (2) ◽  
pp. 53-56
Author(s):  
Y V Khasanova ◽  
A B Galkina ◽  
A A Nelaeva ◽  
I V Medvedeva

Aim: to study the role and relationship of lipid metabolism and levels of proinflammatory cytokines in patients with type 2 diabetes mellitus (DM2) with diabetic nephropathy (DN), depending on the stage of chronic kidney disease (CKD). Materials and Methods: a total of 240 patients with type 2 diabetes in the early stages of DN and CKD were studied. Results: in patients with type 2 diabetes development of DN was associated with an increased level of proinflammatory cytokines and lipid abnormalities (hypertriglyceridemia). We found a negative correlation between the level of triglycerides (TG) and glomerular filtration rate (GFR) (r = -0,43) and a direct correlation between the level of IL-6 and TG (r = 0,48). Conclusions: increased levels of proinflammatory cytokines and triglycerides increase the risk of development and progression of DN and CKD.


2007 ◽  
Vol 21 (5) ◽  
Author(s):  
Xiaoxin X. Wang ◽  
Tao Jiang ◽  
Hideaki Takahashi ◽  
Jinping Li ◽  
Mieko Iwahashi ◽  
...  

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