Potent long-acting rhFGF21 analog for treatment of diabetic nephropathy in db/db and DIO mice

Zhao, Lingyue; Wang, Huiyan; Xie, Jingyuan; Chen, Zilu; Li, Xiaokun; Niu, Jianlou

doi:10.1186/s12896-017-0368-z

Cited by 21 publications

(21 citation statements)

References 31 publications

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“…1 E, F; P < 0.01 for both). Kidney function was assessed by using urine albumin‐to‐creatinine ratio (ACR), as described previously (15, 16). Our data indicate that the ACR in young MR mice was 46% lower than that in young CF mice, but was not statistically significant (CF: 60 ± 52 mg/g vs. MR: 32 ± 19 mg/g; P = 0.11).…”

Section: Resultsmentioning

confidence: 99%

Dietary methionine restriction modulates renal response and attenuates kidney injury in mice

2018

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Methionine restriction (MR) extends the lifespan across several species, such as rodents, fruit flies, roundworms, and yeast. MR studies have been conducted on various rodent organs, such as liver, adipose tissue, heart, bones, and skeletal muscle, to elucidate its benefits to the healthspan; however, studies of the direct effect of MR on kidneys are lacking. To investigate the renal effects of MR, we used young and aged unilateral nephrectomized and 5/6 nephrectomized (5/6Nx) mice. Our studies indicated that MR mice experienced polydipsia and polyuria compared with control-fed counterparts. Urine albumin, creatinine, albumin-to-creatinine ratio, sulfur amino acids, and electrolytes were reduced in MR mice. Kidneys of MR mice up-regulated genes that are involved in ion transport, such as Aqp2, Scnn1a, and Slc6a19, which indicated a response to maintain osmotic balance. In addition, we identified renoprotective biomarkers that are affected by MR, such as clusterin and cystatin C. Of importance, MR attenuated kidney injury in 5/6Nx mice by down-regulating inflammation and fibrosis mechanisms. Thus, our studies in mice show the important role of kidneys during MR in maintaining osmotic homeostasis. Moreover, our studies also show that the MR diet delays the progression of kidney disease.-Cooke, D., Ouattara, A., Ables, G. P. Dietary methionine restriction modulates renal response and attenuates kidney injury in mice. FASEB J. 32, 693-702 (2018). www.fasebj.org

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Section: Resultsmentioning

confidence: 99%

Dietary methionine restriction modulates renal response and attenuates kidney injury in mice

2018

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“…In addition to the improvement of systemic metabolic alterations including glucose metabolism, previous reports demonstrated that FGF21 protected against diabetes-induced renal injuries through anti-fibrotic, anti-inflammatory and anti-oxidative stress effects in db/db mice and in mice with diet-induced obesity and type 2 diabetes [ 43 , 44 ]. Therefore, our data also indicated that the LPD might protect against diabetic nephropathy both indirectly and directly via FGF21 induction.…”

Section: Discussionmentioning

confidence: 99%

A low-protein diet exerts a beneficial effect on diabetic status and prevents diabetic nephropathy in Wistar fatty rats, an animal model of type 2 diabetes and obesity

et al. 2018

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“…Furthermore, FGF21 improved renal lipid metabolism and oxidative stress injury. FGF21 gene deletion further enhances the pathological damage while rFGF21 replenishment significantly prevents it [7, 8, 91]. Fenofibrate protects against type 1 DN by FGF21-mediated upregulation of the nuclear factor E2-related factor 2 (Nrf2) antioxidant pathway [92].…”

Section: Fgf21 In Preclinical Experimental Animal Studiesmentioning

confidence: 99%

Fibroblast growth factor 21 in chronic kidney disease

et al. 2018

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Fibroblast growth factor 21 (FGF21) is a member of the endocrine FGF family that acts as a metabolic regulator of both glucose and lipid metabolism. Similar to fibroblast growth factor 23 (FGF23), serum FGF21 levels rise progressively with the loss of renal function, reaching 20 times normal values in end-stage renal disease. In patients with chronic kidney disease (CKD), higher serum FGF21 levels correlate with poorer metabolic profile, higher inflammatory markers, more comorbidities, and higher mortality. The high serum FGF21 levels are above and beyond what can be explained by the loss of FGF21 renal clearance, suggesting increased production and/or impaired non-renal clearance. In diabetic nephropathy, serum FGF21 levels correlate with the severity of albuminuria and faster loss of glomerular filtrate rate and can potentially be a biomarker of poor prognostic. The observational and associative human data contrast sharply with in vitro and in vivo preclinical experimental data, which is more in line with a protective role of FGF21 in chronic nephropathies. We here review the physiology of FGF21, and the literature regarding its behavior in CKD with particular focus on diabetic nephropathy. Finally, we speculate on the role of FGF21 in CKD.

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Potent long-acting rhFGF21 analog for treatment of diabetic nephropathy in db/db and DIO mice

Cited by 21 publications

References 31 publications

Dietary methionine restriction modulates renal response and attenuates kidney injury in mice

Dietary methionine restriction modulates renal response and attenuates kidney injury in mice

A low-protein diet exerts a beneficial effect on diabetic status and prevents diabetic nephropathy in Wistar fatty rats, an animal model of type 2 diabetes and obesity

Fibroblast growth factor 21 in chronic kidney disease

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