PMID- 28256090 OWN - NLM STAT- MEDLINE DCOM- 20171130 LR - 20181113 IS - 1474-9726 (Electronic) IS - 1474-9718 (Print) IS - 1474-9718 (Linking) VI - 16 IP - 3 DP - 2017 Jun TI - Sterol regulatory element-binding protein-1c orchestrates metabolic remodeling of white adipose tissue by caloric restriction. PG - 508-517 LID - 10.1111/acel.12576 [doi] AB - Caloric restriction (CR) can delay onset of several age-related pathophysiologies and extend lifespan in various species, including rodents. CR also induces metabolic remodeling involved in activation of lipid metabolism, enhancement of mitochondrial biogenesis, and reduction of oxidative stress in white adipose tissue (WAT). In studies using genetically modified mice with extended lifespans, WAT characteristics influenced mammalian lifespans. However, molecular mechanisms underlying CR-associated metabolic remodeling of WAT remain unclear. Sterol regulatory element-binding protein-1c (Srebp-1c), a master transcription factor of fatty acid (FA) biosynthesis, is responsible for the pathogenesis of fatty liver (steatosis). Our study showed that, under CR conditions, Srebp-1c enhanced mitochondrial biogenesis via increased expression of peroxisome proliferator-activated receptor gamma coactivator-1alpha (Pgc-1alpha) and upregulated expression of proteins involved in FA biosynthesis within WAT. However, via Srebp-1c, most of these CR-associated metabolic alterations were not observed in other tissues, including the liver. Moreover, our data indicated that Srebp-1c may be an important factor both for CR-associated suppression of oxidative stress, through increased synthesis of glutathione in WAT, and for the prolongevity action of CR. Our results strongly suggested that Srebp-1c, the primary FA biosynthesis-promoting transcriptional factor implicated in fatty liver disease, is also the food shortage-responsive factor in WAT. This indicated that Srebp-1c is a key regulator of metabolic remodeling leading to the beneficial effects of CR. CI - (c) 2017 The Authors. Aging Cell published by the Anatomical Society and John Wiley & Sons Ltd. FAU - Fujii, Namiki AU - Fujii N AD - Laboratory of Molecular Pathology and Metabolic Disease, Faculty of Pharmaceutical Sciences, Tokyo University of Science, 2641 Yamazaki, Noda, Chiba, 278-8510, Japan. FAU - Narita, Takumi AU - Narita T AD - Laboratory of Molecular Pathology and Metabolic Disease, Faculty of Pharmaceutical Sciences, Tokyo University of Science, 2641 Yamazaki, Noda, Chiba, 278-8510, Japan. AD - Translational Research Center, Research Institute of Science and Technology, Tokyo University of Science, 2641 Yamazaki, Noda, Chiba, 278-8510, Japan. FAU - Okita, Naoyuki AU - Okita N AD - Translational Research Center, Research Institute of Science and Technology, Tokyo University of Science, 2641 Yamazaki, Noda, Chiba, 278-8510, Japan. AD - Department of Internal Medicine Research, Sasaki Institute, Sasaki Foundation, 2-2 Kandasurugadai, Chiyoda-ku, Tokyo, 101-0062, Japan. FAU - Kobayashi, Masaki AU - Kobayashi M AD - Laboratory of Molecular Pathology and Metabolic Disease, Faculty of Pharmaceutical Sciences, Tokyo University of Science, 2641 Yamazaki, Noda, Chiba, 278-8510, Japan. AD - Translational Research Center, Research Institute of Science and Technology, Tokyo University of Science, 2641 Yamazaki, Noda, Chiba, 278-8510, Japan. FAU - Furuta, Yurika AU - Furuta Y AD - Laboratory of Molecular Pathology and Metabolic Disease, Faculty of Pharmaceutical Sciences, Tokyo University of Science, 2641 Yamazaki, Noda, Chiba, 278-8510, Japan. FAU - Chujo, Yoshikazu AU - Chujo Y AD - Laboratory of Molecular Pathology and Metabolic Disease, Faculty of Pharmaceutical Sciences, Tokyo University of Science, 2641 Yamazaki, Noda, Chiba, 278-8510, Japan. FAU - Sakai, Masahiro AU - Sakai M AD - Laboratory of Molecular Pathology and Metabolic Disease, Faculty of Pharmaceutical Sciences, Tokyo University of Science, 2641 Yamazaki, Noda, Chiba, 278-8510, Japan. FAU - Yamada, Atsushi AU - Yamada A AD - Laboratory of Molecular Pathology and Metabolic Disease, Faculty of Pharmaceutical Sciences, Tokyo University of Science, 2641 Yamazaki, Noda, Chiba, 278-8510, Japan. FAU - Takeda, Kanae AU - Takeda K AD - Laboratory of Molecular Pathology and Metabolic Disease, Faculty of Pharmaceutical Sciences, Tokyo University of Science, 2641 Yamazaki, Noda, Chiba, 278-8510, Japan. FAU - Konishi, Tomokazu AU - Konishi T AD - Faculty of Bioresource Sciences, Akita Prefectural University, Shimoshinjo, Nakano, Akita, 010-0195, Japan. FAU - Sudo, Yuka AU - Sudo Y AD - Laboratory of Molecular Pathology and Metabolic Disease, Faculty of Pharmaceutical Sciences, Tokyo University of Science, 2641 Yamazaki, Noda, Chiba, 278-8510, Japan. AD - Translational Research Center, Research Institute of Science and Technology, Tokyo University of Science, 2641 Yamazaki, Noda, Chiba, 278-8510, Japan. FAU - Shimokawa, Isao AU - Shimokawa I AD - Translational Research Center, Research Institute of Science and Technology, Tokyo University of Science, 2641 Yamazaki, Noda, Chiba, 278-8510, Japan. AD - Department of Pathology, Nagasaki University Graduate School of Biomedical Sciences, 1-12-4 Sakamoto, Nagasaki, 852-8523, Japan. FAU - Higami, Yoshikazu AU - Higami Y AD - Laboratory of Molecular Pathology and Metabolic Disease, Faculty of Pharmaceutical Sciences, Tokyo University of Science, 2641 Yamazaki, Noda, Chiba, 278-8510, Japan. AD - Translational Research Center, Research Institute of Science and Technology, Tokyo University of Science, 2641 Yamazaki, Noda, Chiba, 278-8510, Japan. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20170303 PL - England TA - Aging Cell JT - Aging cell JID - 101130839 RN - 0 (Fatty Acids) RN - 0 (Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha) RN - 0 (Ppargc1a protein, mouse) RN - 0 (Srebf1 protein, mouse) RN - 0 (Sterol Regulatory Element Binding Protein 1) RN - GAN16C9B8O (Glutathione) SB - IM MH - Adipose Tissue, White/*metabolism MH - Aging/*metabolism MH - Animals MH - *Caloric Restriction MH - Embryo, Mammalian MH - Fatty Acids/*biosynthesis MH - Female MH - Fibroblasts/cytology/metabolism MH - Gene Expression Regulation MH - Glutathione/biosynthesis MH - Male MH - Mice MH - Mice, Knockout MH - Mitochondria/metabolism MH - Organelle Biogenesis MH - Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha/genetics/metabolism MH - Primary Cell Culture MH - Signal Transduction MH - Sterol Regulatory Element Binding Protein 1/deficiency/*genetics PMC - PMC5418191 OTO - NOTNLM OT - caloric restriction (CR) OT - mitochondria biogenesis OT - oxidative stress OT - peroxisome proliferator-activated receptor gamma coactivator-1alpha (Pgc-1alpha) OT - sterol regulatory element binding protein-1c (Srebp-1c) OT - white adipose tissue (WAT) EDAT- 2017/03/04 06:00 MHDA- 2017/12/01 06:00 PMCR- 2017/06/01 CRDT- 2017/03/04 06:00 PHST- 2017/01/02 00:00 [accepted] PHST- 2017/03/04 06:00 [pubmed] PHST- 2017/12/01 06:00 [medline] PHST- 2017/03/04 06:00 [entrez] PHST- 2017/06/01 00:00 [pmc-release] AID - ACEL12576 [pii] AID - 10.1111/acel.12576 [doi] PST - ppublish SO - Aging Cell. 2017 Jun;16(3):508-517. doi: 10.1111/acel.12576. Epub 2017 Mar 3.