Related Experiment Video

Updated: Aug 5, 2026

Comparative Proteomic Analysis of Whole Kidney, Medulla, and Cortical Tubules in Diabetic Pathogenesis of Kidney Injury in Mice
10:31

Comparative Proteomic Analysis of Whole Kidney, Medulla, and Cortical Tubules in Diabetic Pathogenesis of Kidney Injury in Mice

Published on: May 2, 2025

ANGPTL4 Exacerbates Renal Injury in Diabetic Kidney Disease by Impairing Podocyte Lipophagy via Compromised Lysosomal

Xiaojing Liu1, Shimin Jiang1, Zhenkun Yang2

  • 1Department of Nephrology, China-Japan Friendship Hospital, Beijing, China.

Advanced Science (Weinheim, Baden-Wurttemberg, Germany)
|July 27, 2026
PubMed

Insights

Diabetic kidney disease involves podocyte injury due to impaired lipid clearance. Angiopoietin-like protein 4 (ANGPTL4) exacerbates this by disrupting lysosomal function and lipophagy, contributing to kidney disease progression.

Area of Science:

  • Nephrology
  • Cell Biology
  • Metabolic Diseases

Background:

  • Diabetic kidney disease (DKD) progression is linked to podocyte injury.
  • Intracellular lipid accumulation and impaired autophagy contribute to podocyte dysfunction in DKD.

Purpose of the Study:

  • To investigate the role of angiopoietin-like protein 4 (ANGPTL4) in podocyte lipophagy and DKD.
  • To elucidate the molecular mechanisms by which ANGPTL4 affects podocyte lipid metabolism and homeostasis.

Main Methods:

  • Analysis of renal biopsies from DKD patients.
  • In vitro studies using immortalized human podocytes exposed to high glucose and palmitic acid (HGPA).
  • Assessment of ANGPTL4 expression, autophagic flux, lysosomal function, and lipid droplet accumulation. Mechanistic studies involved TFEB localization and activity assays.

Main Results:

  • ANGPTL4 is upregulated in DKD podocytes, correlating with proteinuria and renal function decline.
  • HGPA treatment increased ANGPTL4, impaired autophagy, and promoted lipid accumulation in podocytes.
  • ANGPTL4 overexpression disrupted TFEB nuclear localization, increased lysosomal pH, and reduced lysosomal enzyme activity, impairing lipophagy.
  • ANGPTL4 knockdown or neutralization partially restored lysosomal and autophagic function.

Conclusions:

  • ANGPTL4 plays a critical role in impairing lysosome-dependent lipid clearance (lipophagy) in podocytes under diabetic conditions.
  • The ANGPTL4-TFEB pathway links metabolic stress to defective lipid handling and podocyte injury in DKD.
  • Targeting ANGPTL4 may offer a therapeutic strategy for managing DKD progression.
Keywords:
ANGPTL4diabetic kidney diseaselipophagylysosomal dysfunctionpodocytes

Related Concept Videos

Diabetic Nephropathy01:28

Diabetic Nephropathy

Definition Diabetic nephropathy is a chronic kidney complication that results from prolonged hyperglycemia.Prevalence It is the most common cause of chronic kidney disease (CKD) and end-stage renal disease (ESRD) worldwide, affecting up to half of individuals with diabetes.Pathophysiology • Sustained hyperglycemia triggers multiple hemodynamic and metabolic changes in the kidney. • Early in the disease, increased renal blood flow and glomerular hyperfiltration occur due to afferent arteriolar...
Acute Kidney Injury II: Pathophysiology01:29

Acute Kidney Injury II: Pathophysiology

Acute kidney injury (AKI) causes are categorized into three primary categories based on the location of the injury: prerenal, intrarenal (or intrinsic), and postrenal causes. This classification guides clinical management and illustrates how different pathways can impair kidney function.Etiology and Pathophysiology of Acute Kidney Injury1. Prerenal causesEtiology: Prerenal Acute Kidney Injury, the most common type, occurs when reduced blood flow to the kidneys decreases filtration capacity...
External Anatomy of the Kidney01:21

External Anatomy of the Kidney

The kidneys are a pair of bean-shaped organs in the human body that play a critical role in maintaining overall health. They filter out waste products from the blood, regulate blood pressure, maintain electrolyte balance, and stimulate the production of red blood cells.
The kidneys are located in the retroperitoneal space on either side of the vertebral column, protected posteriorly by the 11th and 12th ribs. The right kidney sits slightly lower than the left owing to the presence of the liver...
Acute Kidney Injury IV: Diagnostic Studies and Prevention01:30

Acute Kidney Injury IV: Diagnostic Studies and Prevention

Accurate diagnosis and effective prevention are critical in managing Acute Kidney Injury (AKI), which is linked to high mortality rates ranging from 10% to 80%. Timely recognition of at-risk patients and careful monitoring can significantly reduce the likelihood of kidney damage.Diagnostic Assessments:The diagnostic process starts with a comprehensive medical history to identify prerenal, intrarenal, and postrenal causes.Prerenal causes, such as dehydration, hypotension, or blood loss, should...
Diabetic Retinopathy01:27

Diabetic Retinopathy

DefinitionDiabetic retinopathy is a microvascular complication of diabetes affecting the retinal blood vessels.Risk FactorsDiabetic retinopathy is present in almost all individuals with type 1 diabetes and more than 60% of those with type 2 diabetes after two decades of disease.The risk increases with poor glycemic control, hypertension, dyslipidemia, smoking, pregnancy, and puberty.Although cataracts and glaucoma are also more frequent in people with diabetes, retinopathy remains the leading...
Nephrotic Syndrome I : Introduction01:24

Nephrotic Syndrome I : Introduction

Nephrotic Syndrome is a chronic kidney disorder defined by clinical findings such as severe proteinuria, hypoalbuminemia, hyperlipidemia, and edema. These symptoms result from damage to the glomeruli, the kidney’s filtering units, increasing their permeability to proteins.Definition and Meaning:Proteinuria, defined as the loss of more than 3.5 grams of protein per day in adults, is a crucial feature of nephrotic syndrome. This condition is often accompanied by edema, the accumulation of fluid...