論文 - 詳細
| RRC ID | 36046 |
|---|---|
| 著者 | Kitada M, Ogura Y, Suzuki T, Sen S, Lee SM, Kanasaki K, Kume S, Koya D. |
| タイトル | A very-low-protein diet ameliorates advanced diabetic nephropathy through autophagy induction by suppression of the mTORC1 pathway in Wistar fatty rats, an animal model of type 2 diabetes and obesity. |
| ジャーナル | Diabetologia |
| Abstract |
AIMS/HYPOTHESIS:The efficacy of a low-protein diet (LPD) on diabetic nephropathy is controversial. We aimed to investigate the renoprotective effects of an LPD and the underlying molecular mechanism in a rat model of type 2 diabetes and obesity. METHODS:Diabetic male Wistar fatty (fa/fa) rats (WFRs) were treated with a standard diet (23.84% protein) or an LPD (5.77% protein) for 20 weeks from 24 weeks of age. We investigated the effect of the LPD on renal function, fibrosis, tubular cell damage, inflammation, mitochondrial morphology of proximal tubular cells (PTCs), apoptosis, autophagy and activation of mammalian target of rapamycin complex 1 (mTORC1). RESULTS:Kidney weight, albuminuria, excretion of urinary liver-type fatty acid binding protein, levels of plasma cystatin C and changes in renal histology, including fibrosis, tubular cell damage and inflammation, were aggravated in WFRs compared with non-diabetic Wistar lean rats (WLRs). Fragmented and swelling mitochondria accumulated in PTCs and apoptosis were enhanced in the kidney of WFRs. Immunohistochemical staining of p62 and p-S6 ribosomal protein (p-S6RP) in the tubular lesions of WFRs was increased compared with WLRs. The LPD intervention clearly ameliorated damage as shown by the assessment of renal function and histology, particularly tubulointerstitial damage in diabetic kidneys. Additionally, the 5.77% LPD, but not the 11.46% LPD, significantly suppressed p-S6RP levels and increased microtubule-associated protein light chain 3-II levels in the renal cortex. The LPD intervention partially decreased HbA1c levels in WFRs, and no differences in mean BP were observed among any of the groups. CONCLUSIONS/INTERPRETATION:A very-low-protein diet improved advanced diabetic renal injuries, including tubulointerstitial damage, by restoring autophagy through the suppression of the mTORC1 pathway. |
| 巻・号 | 59(6) |
| ページ | 1307-17 |
| 公開日 | 2016-6-1 |
| DOI | 10.1007/s00125-016-3925-4 |
| PII | 10.1007/s00125-016-3925-4 |
| PMID | 27020449 |
| MeSH | Animals Autophagy / genetics Autophagy / physiology* Diabetes Mellitus, Type 2 / diet therapy* Diabetes Mellitus, Type 2 / metabolism* Diabetes Mellitus, Type 2 / pathology Diabetic Nephropathies / diet therapy* Diabetic Nephropathies / metabolism* Diabetic Nephropathies / pathology Diet, Protein-Restricted* Disease Models, Animal Immunohistochemistry Male Mechanistic Target of Rapamycin Complex 1 Microscopy, Electron, Transmission Multiprotein Complexes / genetics Multiprotein Complexes / metabolism* Obesity / diet therapy Obesity / metabolism Obesity / pathology Rats Rats, Wistar Real-Time Polymerase Chain Reaction TOR Serine-Threonine Kinases / genetics TOR Serine-Threonine Kinases / metabolism* |
| IF | 7.518 |
| 引用数 | 41 |
| WOS 分野 | ENDOCRINOLOGY & METABOLISM |
| リソース情報 | |
| 実験動物マウス | RBRC00806 |