PMID- 32664386
OWN - NLM
STAT- MEDLINE
DCOM- 20210308
LR  - 20210308
IS  - 2072-6643 (Electronic)
IS  - 2072-6643 (Linking)
VI  - 12
IP  - 7
DP  - 2020 Jul 10
TI  - Srebp-1c/Fgf21/Pgc-1alpha Axis Regulated by Leptin Signaling in Adipocytes-Possible 
      Mechanism of Caloric Restriction-Associated Metabolic Remodeling of White Adipose 
      Tissue.
LID - 10.3390/nu12072054 [doi]
LID - 2054
AB  - Caloric restriction (CR) improves whole body metabolism, suppresses age-related 
      pathophysiology, and extends lifespan in rodents. Metabolic remodeling, including 
      fatty acid (FA) biosynthesis and mitochondrial biogenesis, in white adipose 
      tissue (WAT) plays an important role in the beneficial effects of CR. We have 
      proposed that CR-induced mitochondrial biogenesis in WAT is mediated by 
      peroxisome proliferator-activated receptor gamma coactivator-1alpha (PGC-1alpha), which is 
      transcriptionally regulated by sterol regulatory element-binding protein 1c 
      (SREBP-1c), a master regulator of FA biosynthesis. We have also proposed that the 
      CR-associated upregulation of SREBP-1 and PGC-1alpha might result from the 
      attenuation of leptin signaling and the upregulation of fibroblast growth factor 
      21 (FGF21) in WAT. However, the detailed molecular mechanisms remain unclear. 
      Here, we interrogate the regulatory mechanisms involving leptin signaling, 
      SREBP-1c, FGF21, and PGC-1alpha using Srebp-1c knockout (KO) mice, mouse embryonic 
      fibroblasts, and 3T3-L1 adipocytes, by altering the expression of SREBP-1c or 
      FGF21. We show that a reduction in leptin signaling induces the expression of 
      proteins involved in FA biosynthesis and mitochondrial biogenesis via SREBP-1c in 
      adipocytes. The upregulation of SREBP-1c activates PGC-1alpha transcription via 
      FGF21, but it is unlikely that the FGF21-associated upregulation of PGC-1alpha 
      expression is a predominant contributor to mitochondrial biogenesis in 
      adipocytes.
FAU - Kobayashi, Masaki
AU  - Kobayashi M
AUID- ORCID: 0000-0002-0985-0322
AD  - Laboratory of Molecular Pathology and Metabolic Disease, Faculty of 
      Pharmaceutical Sciences, Tokyo University of Science, Chiba 278-8510, Japan.
FAU - Uta, Seira
AU  - Uta S
AD  - Laboratory of Molecular Pathology and Metabolic Disease, Faculty of 
      Pharmaceutical Sciences, Tokyo University of Science, Chiba 278-8510, Japan.
FAU - Otsubo, Minami
AU  - Otsubo M
AD  - Laboratory of Molecular Pathology and Metabolic Disease, Faculty of 
      Pharmaceutical Sciences, Tokyo University of Science, Chiba 278-8510, Japan.
FAU - Deguchi, Yusuke
AU  - Deguchi Y
AD  - Laboratory of Molecular Pathology and Metabolic Disease, Faculty of 
      Pharmaceutical Sciences, Tokyo University of Science, Chiba 278-8510, Japan.
FAU - Tagawa, Ryoma
AU  - Tagawa R
AD  - Laboratory of Molecular Pathology and Metabolic Disease, Faculty of 
      Pharmaceutical Sciences, Tokyo University of Science, Chiba 278-8510, Japan.
FAU - Mizunoe, Yuhei
AU  - Mizunoe Y
AUID- ORCID: 0000-0001-6716-1544
AD  - Department of Internal Medicine (Endocrinology and Metabolism), Faculty of 
      Medicine, University of Tsukuba, Ibaraki 305-8575, Japan.
FAU - Nakagawa, Yoshimi
AU  - Nakagawa Y
AUID- ORCID: 0000-0001-8710-5232
AD  - Division of Complex Biosystem Research, Department of Research and Development, 
      Institute of Natural Medicine, University of Toyama, Toyama 930-0194, Japan.
FAU - Shimano, Hitoshi
AU  - Shimano H
AUID- ORCID: 0000-0002-5562-5572
AD  - Department of Internal Medicine (Endocrinology and Metabolism), Faculty of 
      Medicine, University of Tsukuba, Ibaraki 305-8575, Japan.
AD  - Life Science Center for Survival Dynamics, Tsukuba Advanced Research Alliance 
      (TARA), University of Tsukuba, Ibaraki 305-8575, Japan.
AD  - AMED-CREST, Japan Agency for Medical Research and Development (AMED), Tokyo 
      100-1004, Japan.
FAU - Higami, Yoshikazu
AU  - Higami Y
AD  - Laboratory of Molecular Pathology and Metabolic Disease, Faculty of 
      Pharmaceutical Sciences, Tokyo University of Science, Chiba 278-8510, Japan.
AD  - Research Institute for Biomedical Sciences, Tokyo University of Science, Chiba 
      278-8510, Japan.
LA  - eng
GR  - Grants-in-Aid for Scientific Research (B) (No. 17H02179)/Japan Society for the 
      Promotion of Science/
PT  - Journal Article
DEP - 20200710
PL  - Switzerland
TA  - Nutrients
JT  - Nutrients
JID - 101521595
RN  - 0 (Fatty Acids)
RN  - 0 (Leptin)
RN  - 0 (Sterol Regulatory Element Binding Protein 1)
RN  - 0 (Transcription Factors)
RN  - 0 (fibroblast growth factor 21)
RN  - 0 (peroxisome-proliferator-activated receptor-gamma coactivator-1)
RN  - 62031-54-3 (Fibroblast Growth Factors)
SB  - IM
MH  - 3T3-L1 Cells
MH  - Adipocytes/*metabolism
MH  - Adipose Tissue, White/*metabolism
MH  - Animals
MH  - Caloric Restriction/*methods
MH  - Fatty Acids/metabolism
MH  - Fibroblast Growth Factors/*metabolism
MH  - Leptin/metabolism
MH  - Lipogenesis
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Mice, Knockout
MH  - Mitochondria/metabolism
MH  - Organelle Biogenesis
MH  - Sterol Regulatory Element Binding Protein 1/*metabolism
MH  - Transcription Factors/*metabolism
MH  - Up-Regulation
PMC - PMC7400870
OTO - NOTNLM
OT  - adipocyte
OT  - caloric restriction
OT  - fatty acid biosynthesis
OT  - mitochondrial biogenesis
COIS- All authors declare no conflict of interest.
EDAT- 2020/07/16 06:00
MHDA- 2021/03/09 06:00
PMCR- 2020/07/01
CRDT- 2020/07/16 06:00
PHST- 2020/06/06 00:00 [received]
PHST- 2020/07/04 00:00 [revised]
PHST- 2020/07/08 00:00 [accepted]
PHST- 2020/07/16 06:00 [entrez]
PHST- 2020/07/16 06:00 [pubmed]
PHST- 2021/03/09 06:00 [medline]
PHST- 2020/07/01 00:00 [pmc-release]
AID - nu12072054 [pii]
AID - nutrients-12-02054 [pii]
AID - 10.3390/nu12072054 [doi]
PST - epublish
SO  - Nutrients. 2020 Jul 10;12(7):2054. doi: 10.3390/nu12072054.