Introduction: Obesity is associated with lifestyle diseases such as type 2 diabetes and organ complications including kidney disease. Childhood diet has a great influence on the development of obesity and its related disorders. Rice endosperm protein (REP) has been reported to improve lipid metabolism and suppress the progression of diabetic kidney disease in animal models. Therefore, we aimed to clarify the effects of REP intake during childhood on the development of high-fat-diet (HFD)-induced obesity and its related disorders during adulthood in mice.

Methods: Four-week-old male C57BL/6J mice were pair-fed a normal-fat diet containing casein or REP for 6 weeks (childhood), and subsequently, an HFD containing casein or REP for 12 weeks (adulthood). Mice were then tested for oral glucose tolerance and subjected to the analyses of growth status, biochemical parameters, kidney histology, and fecal gut microbiota by 16S rRNA gene sequencing. Antibacterial activity of REP-derived peptides against gut microbiota was evaluated in vitro.

Results: Mice fed REP in childhood showed less increase in body weight, total fat mass, blood pressure, serum total cholesterol, triglyceride, and lipopolysaccharide (LPS)-binding protein, and better glucose tolerance than those fed casein in childhood followed by HFD with casein or REP. Furthermore, HFD-induced glomerular hypertrophy, mesangial expansion, and vacuolar formation in proximal tubules were suppressed in mice fed REP than those fed casein in childhood. The intake of REP in childhood ameliorated dysbiosis caused by HFD. Additionally, REP-derived peptides showed antibacterial activity against E. coli, a major producer of LPS.

Conclusion: These results indicate that the intake of REP during childhood can inhibit the progression of HFD-induced metabolic disorders and kidney disease in adulthood, probably through the effects of REP on gut microbiota.


Y. Higuchi: None. M. Hosojima: Research Support; Self; Astellas Pharma Inc., Biotech Japan Corporation, Daiichi Sankyo Co.,Ltd., Eli Lilly Japan K.K., Forica Foods Co.,Ltd., Kameda Seika Co.,Ltd., Kyowa Hakko Kirin Co., Ltd., Mitsubishi Tanabe Pharma Corporation, MSD K.K., Novo Nordisc Pharma Ltd., Sato Foods Industries Co.,Ltd., Taisho Toyama Pharmaceutical.Co.,Ltd., Takeda Pharmaceutical Co.,Ltd. H. Kabasawa: Research Support; Self; Astellas Pharma Inc., Biotec Japan Corporation, Daiichi Sankyo Company, Limited, Forica Foods CO.,LTD., KAMEDA SEIKA CO., LTD., Kyowa Hakko Kirin Co., Ltd., Mitsubishi Tanabe Pharma Corporation, MSD K.K, Novo Nordisc Pharma Ltd, Sato Foods Industries CO.,LTD., Taisho Toyama Pharmaceutical.CO.,LTD., Takeda Pharmaceutical Company Limited. S. Kuwahara: None. R. Kaseda: None. H. Arao: None. T. Tanaka: None. I. Narita: None. A. Saito: None.

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