title: Atgl deficiency induces podocyte apoptosis and leads to glomerular filtration barrier damage.
abstract: Abnormal lipid metabolism, renal lipid accumulation and lipotoxicity are associated with the pathological features of glomerulopathy. However, the mechanisms by which lipid accumulation leads to the development or progression of this disease have not been fully elucidated. In this work, we have identified a role for the rate-limiting enzyme in lipolysis, adipose triglyceride lipase (ATGL; also called patatin-like phospholipase domain-containing protein 2), in renal lipid metabolism and kidney disease. ATGL-deficient (Atgl(-/-)) mice displayed albuminuria, accompanied by ectopic deposition of fat in the kidney. Magnetic resonance imaging demonstrated that the contrast agent gadopentetic acid was retained in kidney tissue, suggesting defects in the glomerular filtration barrier. Furthermore, transmission electron microscopy revealed lipid deposits in the podocyte, along with foot process fusion and morphological changes suggestive of apoptosis. Indeed, shRNA-mediated depletion of ATGL promoted podocyte apoptosis, accompanied by increased levels of intracellular reactive oxygen species (ROS) and F-actin fibre redistribution. These effects could be partially reversed by treatment with the antioxidant N-acetylcysteine. These data suggest that ATGL deficiency induces renal lipid accumulation, proteinuria and glomerular filtration barrier dysfunction and implicate increased intracellular ROS levels in inducing podocyte F-actin rearrangement, foot process fusion and apoptosis that underlie these pathological features.
  
  
  
  Adipose triglyceride lipase, EC3.1.1.3.
authors.affiliation: Department of Endocrinology, Southwest Hospital, Third Military Medical University, Chongqing, China.
authors.forename: Wen
authors.initials: W
authors.lastname: Chen
authors.affiliation: Department of Endocrinology, Southwest Hospital, Third Military Medical University, Chongqing, China.
authors.forename: Youzhao
authors.initials: Y
authors.lastname: Jiang
authors.affiliation: Department of Gynaecology and Obstetrics, Daping Hospital, Third Military Medical University, Chongqing, China.
authors.forename: Jian
authors.initials: J
authors.lastname: Han
authors.affiliation: Department of Endocrinology, Southwest Hospital, State Key Laboratory of Trauma, Burns and Combined Injury, Third Military Medical University, Chongqing, China.
authors.forename: Jiongyu
authors.initials: J
authors.lastname: Hu
authors.affiliation: Department of Burns and Plastic Surgery, the General Hospital of the Chinese People's Armed Police Forces, Beijing, China.
authors.forename: Ting
authors.initials: T
authors.lastname: He
authors.affiliation: Institute of Burn Research, Southwest Hospital, State Key Laboratory of Trauma, Burns and Combined Injury, Third Military Medical University, Chongqing, China.
authors.forename: Tiantian
authors.initials: T
authors.lastname: Yan
authors.affiliation: Department of Endocrinology, Southwest Hospital, Third Military Medical University, Chongqing, China.
authors.forename: Na
authors.initials: N
authors.lastname: Huang
authors.affiliation: Institute of Burn Research, Southwest Hospital, State Key Laboratory of Trauma, Burns and Combined Injury, Third Military Medical University, Chongqing, China.
authors.forename: Qiong
authors.initials: Q
authors.lastname: Zhang
authors.affiliation: Center for Outcomes Research and Evaluation, Yale-New Haven Hospital, CT, USA.
authors.forename: Hao
authors.initials: H
authors.lastname: Mei
authors.affiliation: Department of Endocrinology, 169th Hospital of PLA, Hengyang, Hunan, China.
authors.forename: Yong
authors.initials: Y
authors.lastname: Liao
authors.affiliation: Institute of Burn Research, Southwest Hospital, State Key Laboratory of Trauma, Burns and Combined Injury, Third Military Medical University, Chongqing, China.
authors.forename: Yuesheng
authors.initials: Y
authors.lastname: Huang
authors.affiliation: Department of Endocrinology, Southwest Hospital, Third Military Medical University, Chongqing, China.
authors.forename: Bing
authors.initials: B
authors.lastname: Chen
mesh_terms: D000111:Acetylcysteine / Q000494:pharmacology; D000199:Actins / Q000235:genetics / Q000378:metabolism; D000419:Albuminuria / Q000000981:diagnostic imaging / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects; D015870:Gene Expression; D005919:Glomerular Filtration Rate; D007674:Kidney Diseases / Q000000981:diagnostic imaging / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology; D008049:Lipase / Q000037:antagonists & inhibitors / Q000172:deficiency / Q000235:genetics*; D050356:Lipid Metabolism / Q000187:drug effects; D008066:Lipolysis / Q000187:drug effects; D008279:Magnetic Resonance Imaging; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D050199:Podocytes / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D034741:RNA, Small Interfering / Q000235:genetics / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000037:antagonists & inhibitors / Q000378:metabolism; D000217:Acyltransferases
chemical_list: D000111:Acetylcysteine; D000199:Actins; D000975:Antioxidants; D008049:Lipase; D034741:RNA, Small Interfering; D017382:Reactive Oxygen Species; C494445:PNPLA2 protein, mouse; D000217:Acyltransferases
keywords: 
  ATGL
  ; 
  ROS
  ; glomerular filtration barrier; mitochondrion; podocyte apoptosis