PMID- 32115557
OWN - NLM
STAT- MEDLINE
DCOM- 20200922
LR  - 20200922
IS  - 1347-5231 (Electronic)
IS  - 0031-6903 (Linking)
VI  - 140
IP  - 3
DP  - 2020
TI  - [Metabolic Alteration in Aging Process: Metabolic Remodeling in White Adipose 
      Tissue by Caloric Restriction].
PG  - 383-389
LID - 10.1248/yakushi.19-00193-2 [doi]
AB  - Caloric restriction (CR) improves whole-body metabolism, suppresses various 
      age-related pathophysiological changes, and extends lifespan. The beneficial 
      actions of CR are regulated in growth hormone (GH)/insulin-like growth factor-1 
      (IGF-1) signal-dependent and -independent manners. To clarify the 
      GH/IGF-1-independent mechanism, we compared gene expression profiles in white 
      adipose tissue (WAT) between CR and GH/IGF-1 suppression, and found that CR 
      upregulated sterol regulatory element-binding protein 1c (SREBP-1c) regulatory 
      gene expression. To validate the impact of SREBP-1c as a beneficial mediator of 
      CR, we compared the responses to CR between wild-type and SREBP-1c knockout (KO) 
      mice. CR extended lifespan, upregulated gene expression involved in FA 
      biosynthesis, activated mitochondrial biogenesis, and suppressed oxidative stress 
      predominantly in WAT. In contrast, most of these findings were not observed in KO 
      mice. Furthermore, SREBP-1c was implicated in CR-associated mitochondrial 
      activation through upregulation of peroxisome proliferator-activated receptor gamma 
      coactivator-1alpha (PGC-1alpha), a master regulator of mitochondrial biogenesis. 
      Sirtuin-3 (SIRT3) regulates mitochondrial quality and is also involved in the 
      beneficial actions of CR. We observed that CR upregulated the mature form of 
      SIRT3 protein and mitochondrial intermediate peptidase (MIPEP), a mitochondrial 
      signal peptidase (MtSPase), in WAT. MIPEP cleaved precursor form of SIRT3 to 
      mature form, and activated certain mitochondrial matrix proteins, suggesting that 
      MIPEP might contribute to maintenance of mitochondrial quality during CR via 
      SIRT3 activation. Taken together, CR induces SREBP-1c-dependent metabolic 
      remodeling, including enhancement of FA biosynthesis and mitochondrial 
      activation, via PGC-1alpha, and improvement of mitochondria quality via Mipep in WAT, 
      resulting in beneficial actions.
FAU - Kobayashi, Masaki
AU  - Kobayashi M
AD  - Laboratory of Molecular Pathology and Metabolic Disease, Department of Medical 
      and Life Science, Faculty of Pharmaceutical Sciences, Tokyo University of 
      Science.
FAU - Higami, Yoshikazu
AU  - Higami Y
AD  - Laboratory of Molecular Pathology and Metabolic Disease, Department of Medical 
      and Life Science, Faculty of Pharmaceutical Sciences, Tokyo University of 
      Science.
LA  - jpn
PT  - Journal Article
PT  - Review
PL  - Japan
TA  - Yakugaku Zasshi
JT  - Yakugaku zasshi : Journal of the Pharmaceutical Society of Japan
JID - 0413613
RN  - 0 (Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha)
RN  - 0 (Sterol Regulatory Element Binding Protein 1)
RN  - EC 3.5.1.- (Sirtuin 3)
SB  - IM
MH  - Adipose Tissue, White/*metabolism
MH  - Aging/*metabolism
MH  - Animals
MH  - *Caloric Restriction
MH  - Gene Expression
MH  - Humans
MH  - Longevity
MH  - Mice
MH  - Organelle Biogenesis
MH  - Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha/metabolism
MH  - Sirtuin 3/metabolism
MH  - Sterol Regulatory Element Binding Protein 1/genetics/metabolism
MH  - Up-Regulation
OTO - NOTNLM
OT  - caloric restriction (CR)
OT  - fatty acid biosynthesis
OT  - mitochondria
OT  - white adipose tissue (WAT)
EDAT- 2020/03/03 06:00
MHDA- 2020/09/23 06:00
CRDT- 2020/03/03 06:00
PHST- 2020/03/03 06:00 [entrez]
PHST- 2020/03/03 06:00 [pubmed]
PHST- 2020/09/23 06:00 [medline]
AID - 10.1248/yakushi.19-00193-2 [doi]
PST - ppublish
SO  - Yakugaku Zasshi. 2020;140(3):383-389. doi: 10.1248/yakushi.19-00193-2.