title: Adipocytes play an etiological role in the podocytopathy of high-fat diet-fed rats.
abstract: Obesity is a risk factor that promotes progressive kidney disease. Studies have shown that an adipocytokine imbalance contributes to impaired renal function in humans and animals, but the underlying interplay between adipocytokines and renal injury remains to be elucidated. We aimed to investigate the mechanisms linking obesity to chronic kidney disease. We assessed renal function in high-fat (HF) diet-fed and normal diet-fed rats, and the effects of preadipocyte- and adipocyte-conditioned medium on cultured podocytes. HF diet-fed and normal diet-fed Sprague Dawley rats were used to analyze the changes in plasma BUN, creatinine, urine protein and renal histology. Additionally, podocytes were incubated with preadipocyte- or adipocyte-conditioned medium to investigate the effects on podocyte morphology and protein expression. In the HF diet group, 24 h urinary protein excretion (357.5 ± 64.2 mg/day vs 115.9 ± 12.4 mg/day, P < 0.05) and the urine protein/creatinine ratio were significantly higher (1.76 ± 0.22 vs 1.09 ± 0.15, P < 0.05), increased kidney weight (3.54 ± 0.04 g vs 3.38 ± 0.04 g, P < 0.05) and the glomerular volume and podocyte effacement increased by electron microscopy. Increased renal expression of desmin and decreased renal expression of CD2AP and nephrin were also seen in the HF diet group (P < 0.05). Furthermore, we found that adipocyte-conditioned medium-treated podocytes showed increased desmin expression and decreased CD2AP and nephrin expression compared with that in preadipocyte-conditioned medium-treated controls (P < 0.05). These findings show that adipocyte-derived factor(s) can modulate renal function. Adipocyte-derived factors play an important role in obesity-related podocytopathy.
authors.affiliation: Division of NephrologyDepartment of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan.|Faculty of MedicineNational Yang-Ming University, Taipei, Taiwan.
authors.forename: Jinn-Yang
authors.initials: JY
authors.lastname: Chen
authors.affiliation: Institute of PhysiologyNational Yang-Ming University, Taipei, Taiwan.|Division of NephrologyWen-Lin Hemodialysis Unit, Taipei, Taiwan.
authors.forename: Deng-Yuan
authors.initials: DY
authors.lastname: Jian
authors.affiliation: Institute of PhysiologyNational Yang-Ming University, Taipei, Taiwan.
authors.forename: Chih-Chan
authors.initials: CC
authors.lastname: Lien
authors.affiliation: Institute of PhysiologyNational Yang-Ming University, Taipei, Taiwan.
authors.forename: Yu-Ting
authors.initials: YT
authors.lastname: Lin
authors.affiliation: Institute of PhysiologyNational Yang-Ming University, Taipei, Taiwan.
authors.forename: Ching-Heng
authors.initials: CH
authors.lastname: Ting
authors.affiliation: Institute of PhysiologyNational Yang-Ming University, Taipei, Taiwan.
authors.forename: Luen-Kui
authors.initials: LK
authors.lastname: Chen
authors.affiliation: Institute of PhysiologyNational Yang-Ming University, Taipei, Taiwan.
authors.forename: Ting-Chia
authors.initials: TC
authors.lastname: Hsu
authors.affiliation: Institute of PhysiologyNational Yang-Ming University, Taipei, Taiwan.
authors.forename: Hsuan-Min
authors.initials: HM
authors.lastname: Huang
authors.affiliation: Institute of PhysiologyNational Yang-Ming University, Taipei, Taiwan.
authors.forename: Yu-Ting
authors.initials: YT
authors.lastname: Wu
authors.affiliation: Institute of PhysiologyNational Yang-Ming University, Taipei, Taiwan.
authors.forename: Tse-Ting
authors.initials: TT
authors.lastname: Kuan
authors.affiliation: Department of Medical Research and EducationTaipei Veterans General Hospital, Taipei, Taiwan.|Section of NephrologyDepartment of Internal Medicine, Heping Branch, Taipei City Hospital, Taipei, Taiwan.
authors.forename: Yu-Wen
authors.initials: YW
authors.lastname: Chao
authors.affiliation: Department of Bioscience TechnologyCollege of Science, Chung Yuan Christian University, Chung Li District, Taoyuan City, Taiwan.
authors.forename: Liang-Yi
authors.initials: LY
authors.lastname: Wu
authors.affiliation: Faculty of MedicineNational Yang-Ming University, Taipei, Taiwan.
authors.forename: Seng-Wong
authors.initials: SW
authors.lastname: Huang
authors.affiliation: Institute of PhysiologyNational Yang-Ming University, Taipei, Taiwan ccjuan@ym.edu.tw.|Department of Medical Research and EducationTaipei Veterans General Hospital, Taipei, Taiwan.|Department of Education and ResearchTaipei City Hospital, Taipei, Taiwan.
authors.forename: Chi-Chang
authors.initials: CC
authors.lastname: Juan
mesh_terms: D041721:3T3-L1 Cells; D052438:Adipocytes, White / Q000378:metabolism / Q000473:pathology; D050154:Adiposity; D000818:Animals; D015415:Biomarkers / Q000097:blood / Q000378:metabolism / Q000652:urine; D002460:Cell Line; D017077:Culture Media, Conditioned; D059305:Diet, High-Fat / Q000009:adverse effects; D004195:Disease Models, Animal; D018450:Disease Progression; D005786:Gene Expression Regulation; D007333:Insulin Resistance; D050152:Intra-Abdominal Fat / Q000378:metabolism / Q000473:pathology*; D007672:Kidney Cortex / Q000378:metabolism / Q000473:pathology* / Q000503:physiopathology / Q000648:ultrastructure; D008297:Male; D051379:Mice; D046529:Microscopy, Electron, Transmission; D009765:Obesity / Q000209:etiology / Q000503:physiopathology*; D009929:Organ Size; D050199:Podocytes / Q000378:metabolism / Q000473:pathology* / Q000648:ultrastructure; D017207:Rats, Sprague-Dawley; D051436:Renal Insufficiency, Chronic / Q000000981:diagnostic imaging / Q000378:metabolism / Q000473:pathology* / Q000503:physiopathology
chemical_list: D015415:Biomarkers; D017077:Culture Media, Conditioned
keywords: adipocytes; adipocytokine; high-fat diet; podocytopathy; visceral fat