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SREBP-1c-Dependent Metabolic Remodeling of White Adipose Tissue by Caloric Restriction

1
Laboratory of Molecular Pathology and Metabolic Disease, Faculty of Pharmaceutical Sciences, Tokyo University of Science, 2641 Yamazaki, Noda, Chiba 278-8510, Japan
2
Translational Research Center, Research Institute of Science and Technology, Tokyo University of Science, 2641 Yamazaki, Noda, Chiba 278-8510, Japan
3
Epidemiology and Prevention Division, Research Center for Cancer Prevention and Screening, National Cancer Center, Tsukiji, Chuo-ku, Tokyo 104-0045, Japan
*
Author to whom correspondence should be addressed.
Int. J. Mol. Sci. 2018, 19(11), 3335; https://doi.org/10.3390/ijms19113335
Received: 31 August 2018 / Revised: 21 October 2018 / Accepted: 21 October 2018 / Published: 26 October 2018
(This article belongs to the Special Issue Transcriptional Regulation in Lipid Metabolism)
Caloric restriction (CR) delays the onset of many age-related pathophysiological changes and extends lifespan. White adipose tissue (WAT) is not only a major tissue for energy storage, but also an endocrine tissue that secretes various adipokines. Recent reports have demonstrated that alterations in the characteristics of WAT can impact whole-body metabolism and lifespan. Hence, we hypothesized that functional alterations in WAT may play important roles in the beneficial effects of CR. Previously, using microarray analysis of WAT from CR rats, we found that CR enhances fatty acid (FA) biosynthesis, and identified sterol regulatory element-binding protein 1c (SREBP-1c), a master regulator of FA synthesis, as a mediator of CR. These findings were validated by showing that CR failed to upregulate factors involved in FA biosynthesis and to extend longevity in SREBP-1c knockout mice. Furthermore, we revealed that SREBP-1c is implicated in CR-associated mitochondrial activation through the upregulation of peroxisome proliferator-activated receptor γ coactivator-1α (PGC-1α), a master regulator of mitochondrial biogenesis. Notably, these CR-associated phenotypes were observed only in WAT. We conclude that CR induces SREBP-1c-dependent metabolic remodeling, including the enhancement of FA biosynthesis and mitochondrial activation, via PGC-1α in WAT, resulting in beneficial effects. View Full-Text
Keywords: caloric restriction; white adipose tissue; SREBP-1c; fatty acid synthesis; PGC-1α; mitochondrion caloric restriction; white adipose tissue; SREBP-1c; fatty acid synthesis; PGC-1α; mitochondrion
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Kobayashi, M.; Fujii, N.; Narita, T.; Higami, Y. SREBP-1c-Dependent Metabolic Remodeling of White Adipose Tissue by Caloric Restriction. Int. J. Mol. Sci. 2018, 19, 3335.

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