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Cited by 576

The DOI matches its Crossref record; 11 of the 11 references it cites were found in a registry or an index.

Skeletal Muscle FOXO1 (FKHR) Transgenic Mice Have Less Skeletal Muscle Mass, Down-regulated Type I (Slow Twitch/Red Muscle) Fiber Genes, and Impaired Glycemic Control

Open access
Kamei, Yasutomi, Miura, Shinji, Suzuki, Miki, Kai, Yuko, Mizukami, Junko, Taniguchi, Tomoyasu, Mochida, Keiji, Hata, Tomoko, Matsuda, Junichiro, Aburatani, Hiroyuki, Nishino, Ichizo, Ezaki, Osamu·2004·Journal of Biological Chemistry

Abstract

FOXO1, a member of the FOXO forkhead type transcription factors, is markedly up-regulated in skeletal muscle in energy-deprived states such as fasting and severe diabetes, but its functions in skeletal muscle have remained poorly understood. In this study, we created transgenic mice specifically overexpressing FOXO1 in skeletal muscle. These mice weighed less than the wild-type control mice, had a reduced skeletal muscle mass, and the muscle was paler in color. Microarray analysis revealed that the expression of many genes related to the structural proteins of type I muscles (slow twitch, red muscle) was decreased. Histological analyses showed a marked decrease in size of both type I and type II fibers and a significant decrease in the number of type I fibers in the skeletal muscle of FOXO1 mice. Enhanced gene expression of a lysosomal proteinase, cathepsin L, which is known to be up-regulated during skeletal muscle atrophy, suggested increased protein degradation in the skeletal muscle of FOXO1 mice. Running wheel activity (spontaneous locomotive activity) was significantly reduced in FOXO1 mice compared with control mice. Moreover, the FOXO1 mice showed impaired glycemic control after oral glucose and intraperitoneal insulin administration. These results suggest that FOXO1 negatively regulates skeletal muscle mass and type I fiber gene expression and leads to impaired skeletal muscle function. Activation of FOXO1 may be involved in the pathogenesis of sarcopenia, the age-related decline in muscle mass in humans, which leads to obesity and diabetes.

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Metadata

Authors
Kamei, Y., Miura, S., Suzuki, M., Kai, Y., Mizukami, J., Taniguchi, T., Mochida, K., Hata, T., Matsuda, J., Aburatani, H., Nishino, I., & Ezaki, O.
Venue
Journal of Biological Chemistry
Publisher
Elsevier BV
Published
2004-09
Volume
279
Issue
39
Pages
41114-41123
ISSN
0021-9258 (ISSN-L)
OpenAlex
W2164713351
Cited by
576
References
11
FWCI
6.67
Type
journal article
Language
en
Open access
hybrid

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CoChat. (2026). Citation check: Skeletal Muscle FOXO1 (FKHR) Transgenic Mice Have Less Skeletal Muscle Mass, Down-regulated Type I (Slow Twitch/Red Muscle) Fiber Genes, and Impaired Glycemic Control. https://app.cochat.ai/papers/10.1074/jbc.m400674200
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Kamei, Y., Miura, S., Suzuki, M., Kai, Y., Mizukami, J., Taniguchi, T., Mochida, K., Hata, T., Matsuda, J., Aburatani, H., Nishino, I., & Ezaki, O. (2004). Skeletal Muscle FOXO1 (FKHR) Transgenic Mice Have Less Skeletal Muscle Mass, Down-regulated Type I (Slow Twitch/Red Muscle) Fiber Genes, and Impaired Glycemic Control. Journal of Biological Chemistry. https://doi.org/10.1074/jbc.m400674200

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