title: Attenuation of hyperlipidemia- and diabetes-induced early-stage apoptosis and late-stage renal dysfunction via administration of fibroblast growth factor-21 is associated with suppression of renal inflammation.
abstract: BACKGROUND
  Lipotoxicity is a key feature of the pathogenesis of diabetic kidney disease, and is attributed to excessive lipid accumulation (hyperlipidemia). Increasing evidence suggests that fibroblast growth factor (FGF)21 has a crucial role in lipid metabolism under diabetic conditions.
  
  
  OBJECTIVE
  The present study investigated whether FGF21 can prevent hyperlipidemia- or diabetes-induced renal damage, and if so, the possible mechanism.
  
  
  METHODS
  Mice were injected with free fatty acids (FFAs, 10 mg/10 g body weight) or streptozotocin (150 mg/kg) to establish a lipotoxic model or type 1 diabetic model, respectively. Simultaneously the mice were treated with FGF21 (100 µg/kg) for 10 or 80 days. The kidney weight-to-tibia length ratio and renal function were assessed. Systematic and renal lipid levels were detected by ELISA and Oil Red O staining. Renal apoptosis was examined by TUNEL assay. Inflammation, oxidative stress, and fibrosis were assessed by Western blot.
  
  
  RESULTS
  Acute FFA administration and chronic diabetes were associated with lower kidney-to-tibia length ratio, higher lipid levels, severe renal apoptosis and renal dysfunction. Obvious inflammation, oxidative stress and fibrosis also observed in the kidney of both mice models. Deletion of the fgf21 gene further enhanced the above pathological changes, which were significantly prevented by administration of exogenous FGF21.
  
  
  CONCLUSIONS
  These results suggest that FFA administration and diabetes induced renal damage, which was further enhanced in FGF21 knock-out mice. Administration of FGF21 significantly prevented both FFA- and diabetes-induced renal damage partially by decreasing renal lipid accumulation and suppressing inflammation, oxidative stress, and fibrosis.
authors.affiliation: Chinese-American Research Institute for Diabetic Complications, Wenzhou Medical University, Wenzhou, Zhejiang, China ; Ruian Center of the Chinese-American Research Institute for Diabetic Complications, Third Affiliated Hospital of the Wenzhou Medical University, Wenzhou, Zhejiang, China.
authors.forename: Chi
authors.initials: C
authors.lastname: Zhang
authors.affiliation: Chinese-American Research Institute for Diabetic Complications, Wenzhou Medical University, Wenzhou, Zhejiang, China ; Ruian Center of the Chinese-American Research Institute for Diabetic Complications, Third Affiliated Hospital of the Wenzhou Medical University, Wenzhou, Zhejiang, China ; School of Pharmacy, Wenzhou Medical University, Wenzhou, Zhejiang, China.
authors.forename: Minglong
authors.initials: M
authors.lastname: Shao
authors.affiliation: Ruian Center of the Chinese-American Research Institute for Diabetic Complications, Third Affiliated Hospital of the Wenzhou Medical University, Wenzhou, Zhejiang, China.
authors.forename: Hong
authors.initials: H
authors.lastname: Yang
authors.affiliation: Ruian Center of the Chinese-American Research Institute for Diabetic Complications, Third Affiliated Hospital of the Wenzhou Medical University, Wenzhou, Zhejiang, China.
authors.forename: Liangmiao
authors.initials: L
authors.lastname: Chen
authors.affiliation: Chinese-American Research Institute for Diabetic Complications, Wenzhou Medical University, Wenzhou, Zhejiang, China ; Ruian Center of the Chinese-American Research Institute for Diabetic Complications, Third Affiliated Hospital of the Wenzhou Medical University, Wenzhou, Zhejiang, China.
authors.forename: Lechu
authors.initials: L
authors.lastname: Yu
authors.affiliation: Chinese-American Research Institute for Diabetic Complications, Wenzhou Medical University, Wenzhou, Zhejiang, China ; School of Pharmacy, Wenzhou Medical University, Wenzhou, Zhejiang, China.
authors.forename: Weitao
authors.initials: W
authors.lastname: Cong
authors.affiliation: School of Pharmacy, Wenzhou Medical University, Wenzhou, Zhejiang, China.
authors.forename: Haishan
authors.initials: H
authors.lastname: Tian
authors.affiliation: Chinese-American Research Institute for Diabetic Complications, Wenzhou Medical University, Wenzhou, Zhejiang, China ; Ruian Center of the Chinese-American Research Institute for Diabetic Complications, Third Affiliated Hospital of the Wenzhou Medical University, Wenzhou, Zhejiang, China.
authors.forename: Fangfang
authors.initials: F
authors.lastname: Zhang
authors.affiliation: Chinese-American Research Institute for Diabetic Complications, Wenzhou Medical University, Wenzhou, Zhejiang, China ; Ruian Center of the Chinese-American Research Institute for Diabetic Complications, Third Affiliated Hospital of the Wenzhou Medical University, Wenzhou, Zhejiang, China.
authors.forename: Peng
authors.initials: P
authors.lastname: Cheng
authors.affiliation: Chinese-American Research Institute for Diabetic Complications, Wenzhou Medical University, Wenzhou, Zhejiang, China ; School of Pharmacy, Wenzhou Medical University, Wenzhou, Zhejiang, China.
authors.forename: Litai
authors.initials: L
authors.lastname: Jin
authors.affiliation: Chinese-American Research Institute for Diabetic Complications, Wenzhou Medical University, Wenzhou, Zhejiang, China ; Ruian Center of the Chinese-American Research Institute for Diabetic Complications, Third Affiliated Hospital of the Wenzhou Medical University, Wenzhou, Zhejiang, China ; Kosair Children's Hospital Research Institute at the Department of Pediatrics, University of Louisville, Louisville, Kentucky, United States of America.
authors.forename: Yi
authors.initials: Y
authors.lastname: Tan
authors.affiliation: Chinese-American Research Institute for Diabetic Complications, Wenzhou Medical University, Wenzhou, Zhejiang, China ; School of Pharmacy, Wenzhou Medical University, Wenzhou, Zhejiang, China.
authors.forename: Xiaokun
authors.initials: X
authors.lastname: Li
authors.affiliation: Chinese-American Research Institute for Diabetic Complications, Wenzhou Medical University, Wenzhou, Zhejiang, China ; Ruian Center of the Chinese-American Research Institute for Diabetic Complications, Third Affiliated Hospital of the Wenzhou Medical University, Wenzhou, Zhejiang, China ; Kosair Children's Hospital Research Institute at the Department of Pediatrics, University of Louisville, Louisville, Kentucky, United States of America.
authors.forename: Lu
authors.initials: L
authors.lastname: Cai
authors.affiliation: Chinese-American Research Institute for Diabetic Complications, Wenzhou Medical University, Wenzhou, Zhejiang, China ; Ruian Center of the Chinese-American Research Institute for Diabetic Complications, Third Affiliated Hospital of the Wenzhou Medical University, Wenzhou, Zhejiang, China.
authors.forename: Xuemian
authors.initials: X
authors.lastname: Lu
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D003921:Diabetes Mellitus, Experimental / Q000150:complications / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology; D003928:Diabetic Nephropathies / Q000150:complications / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology; D005227:Fatty Acids / Q000633:toxicity; D005346:Fibroblast Growth Factors / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D005355:Fibrosis; D006949:Hyperlipidemias / Q000150:complications / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology; D006984:Hypertrophy; D007249:Inflammation / Q000150:complications / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology; D007668:Kidney / Q000187:drug effects / Q000473:pathology / Q000503:physiopathology*; D050356:Lipid Metabolism / Q000187:drug effects; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009206:Myocardium / Q000473:pathology; D018384:Oxidative Stress / Q000187:drug effects
chemical_list: D005227:Fatty Acids; C414620:fibroblast growth factor 21; D005346:Fibroblast Growth Factors