A low-protein diet exerts a beneficial effect on diabetic status and prevents diabetic nephropathy in Wistar fatty rats,
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RESEARCH
Open Access
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 Munehiro Kitada1,2*, Yoshio Ogura1, Taeko Suzuki1, Itaru Monno1, Keizo Kanasaki1,2, Ai Watanabe1 and Daisuke Koya1,2
Abstract Background: The objective of this study is to investigate the effects of a low-protein diet (LPD) starting from a young age on diabetic status and renal injury in a rat model of type 2 diabetes and obesity. Methods: Diabetic male Wistar fatty (fa/fa) rats (WFRs) were fed a standard diet (23.84% protein) or an LPD (5.77% protein) for 24 weeks beginning at 6 weeks of age. We investigated the effects of the LPD on total body weight (BW); fat weight (FW); lower-limb muscle weight (MW); several measures of diabetic status, including fasting/ random glucose levels, HOMA-IR and the IPITT; and renal injuries, including renal hypertrophy, albuminuria and histological changes. Additionally, autophagy and activation of mTORC1 were evaluated in the diabetic renal cortex. Furthermore, plasma FGF21 and high-molecular-weight (HMW) adiponectin levels, as well as UCP1 expression levels in brown adipose tissue (BAT), were evaluated. Results: Increases in BW and FW in WFRs were significantly reduced by the LPD, and the LPD resulted in a significant reduction of lower-limb MW in WFRs. The LPD suppressed the elevation of glucose levels in WFRs through improvement of insulin resistance. The LPD also elevated the plasma FGF21 and HMW adiponectin of WFRs, as well as UCP1 expression in the BAT of the animals. Renal hypertrophy, albuminuria, renal histological changes, and increased expression of p62 and phospho-S6 ribosomal protein (p-S6RP) were observed in WFRs compared with the values from WLRs. The LPD clearly prevented the diabetic kidneys from sustaining any damage. Conclusions: The LPD prevented the progression of diabetic status; this effect may have been associated with the reduction of FW and the elevation of plasma FGF21 and HMW adiponectin, as well as UCP1 expression in BAT, resulting in suppression of diabetic nephropathy. However, MW was decreased in rats by the consumption of an LPD from a young age; therefore, further research is needed to resolve the nutritional issue of LPD on decreasing in MW. Keywords: Low-protein diet, Diabetes, Fibroblast growth factor 21, High-molecular-weight adiponectin, Uncoupling protein 1, Diabetic nephropathy
* Correspondence: [email protected] 1 Department of Diabetology and Endocrinology, Kanazawa Medical University, Uchinada, Ishikawa 920-0293, Japan 2 Division of Anticipatory Molecular Food Science and Technology, Medical Research Institute, Kanazawa Medical University, Uchinada, Ishikawa, Japan © The Author(s). 2018 Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you giv
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