Effects of CREG1 on Age-Associated Metabolic Phenotypes and Renal Senescence in Mice
Cellular repressor of E1A-stimulated genes 1 (CREG1) is a secreted glycoprotein that accelerates p16-dependent cellular senescence in vitro. We recently reported the ability of CREG1 to stimulate brown adipogenesis using adipocyte P2-CREG1-transgenic (Tg) mice; however, little is known about the eff...
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doaj-2127d7ceff9e4766bceecdf74d5cf75e2021-01-29T00:02:04ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672021-01-01221276127610.3390/ijms22031276Effects of CREG1 on Age-Associated Metabolic Phenotypes and Renal Senescence in MiceMichihiro Hashimoto0Ayumi Goto1Yuki Endo2Masataka Sugimoto3Jun Ueda4Hitoshi Yamashita5Division of Advanced Medical Science, Asahikawa Medical University, Asahikawa 078-8510, Hokkaido, JapanDepartment of Biomedical Sciences, College of Life and Health Sciences, Chubu University, Kasugai 487-8501, Aichi, JapanDepartment of Biomedical Sciences, College of Life and Health Sciences, Chubu University, Kasugai 487-8501, Aichi, JapanResearch Institute, National Center for Geriatrics and Gerontology, Obu 474-8511, Aichi, JapanDivision of Advanced Medical Science, Asahikawa Medical University, Asahikawa 078-8510, Hokkaido, JapanDepartment of Biomedical Sciences, College of Life and Health Sciences, Chubu University, Kasugai 487-8501, Aichi, JapanCellular repressor of E1A-stimulated genes 1 (CREG1) is a secreted glycoprotein that accelerates p16-dependent cellular senescence in vitro. We recently reported the ability of CREG1 to stimulate brown adipogenesis using adipocyte P2-CREG1-transgenic (Tg) mice; however, little is known about the effect of CREG1 on aging-associated phenotypes. In this study, we investigated the effects of CREG1 on age-related obesity and renal dysfunction in Tg mice. Increased brown fat formation was detected in aged Tg mice, in which age-associated metabolic phenotypes such as body weight gain and increases in blood glucose were improved compared with those in wild-type (WT) mice. Blood CREG1 levels increased significantly in WT mice with age, whereas the age-related increase was suppressed, and its levels were reduced, in the livers and kidneys of Tg mice relative to those in WT mice at 25 months. Intriguingly, the mRNA levels of <i>Ink4a</i>, <i>Arf</i>, and senescence-associated secretory phenotype (SASP)-related genes and p38MAPK activity were significantly lowered in the aged kidneys of Tg mice, in which the morphological abnormalities of glomeruli as well as filtering function seen in WT kidneys were alleviated. These results suggest the involvement of CREG1 in kidney aging and its potential as a target for improving age-related renal dysfunction.https://www.mdpi.com/1422-0067/22/3/1276CREG1cellular senescencerenal dysfunctionbrown adipocyteage-related obesity |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Michihiro Hashimoto Ayumi Goto Yuki Endo Masataka Sugimoto Jun Ueda Hitoshi Yamashita |
spellingShingle |
Michihiro Hashimoto Ayumi Goto Yuki Endo Masataka Sugimoto Jun Ueda Hitoshi Yamashita Effects of CREG1 on Age-Associated Metabolic Phenotypes and Renal Senescence in Mice International Journal of Molecular Sciences CREG1 cellular senescence renal dysfunction brown adipocyte age-related obesity |
author_facet |
Michihiro Hashimoto Ayumi Goto Yuki Endo Masataka Sugimoto Jun Ueda Hitoshi Yamashita |
author_sort |
Michihiro Hashimoto |
title |
Effects of CREG1 on Age-Associated Metabolic Phenotypes and Renal Senescence in Mice |
title_short |
Effects of CREG1 on Age-Associated Metabolic Phenotypes and Renal Senescence in Mice |
title_full |
Effects of CREG1 on Age-Associated Metabolic Phenotypes and Renal Senescence in Mice |
title_fullStr |
Effects of CREG1 on Age-Associated Metabolic Phenotypes and Renal Senescence in Mice |
title_full_unstemmed |
Effects of CREG1 on Age-Associated Metabolic Phenotypes and Renal Senescence in Mice |
title_sort |
effects of creg1 on age-associated metabolic phenotypes and renal senescence in mice |
publisher |
MDPI AG |
series |
International Journal of Molecular Sciences |
issn |
1661-6596 1422-0067 |
publishDate |
2021-01-01 |
description |
Cellular repressor of E1A-stimulated genes 1 (CREG1) is a secreted glycoprotein that accelerates p16-dependent cellular senescence in vitro. We recently reported the ability of CREG1 to stimulate brown adipogenesis using adipocyte P2-CREG1-transgenic (Tg) mice; however, little is known about the effect of CREG1 on aging-associated phenotypes. In this study, we investigated the effects of CREG1 on age-related obesity and renal dysfunction in Tg mice. Increased brown fat formation was detected in aged Tg mice, in which age-associated metabolic phenotypes such as body weight gain and increases in blood glucose were improved compared with those in wild-type (WT) mice. Blood CREG1 levels increased significantly in WT mice with age, whereas the age-related increase was suppressed, and its levels were reduced, in the livers and kidneys of Tg mice relative to those in WT mice at 25 months. Intriguingly, the mRNA levels of <i>Ink4a</i>, <i>Arf</i>, and senescence-associated secretory phenotype (SASP)-related genes and p38MAPK activity were significantly lowered in the aged kidneys of Tg mice, in which the morphological abnormalities of glomeruli as well as filtering function seen in WT kidneys were alleviated. These results suggest the involvement of CREG1 in kidney aging and its potential as a target for improving age-related renal dysfunction. |
topic |
CREG1 cellular senescence renal dysfunction brown adipocyte age-related obesity |
url |
https://www.mdpi.com/1422-0067/22/3/1276 |
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