PMID- 37584358
OWN - NLM
STAT- MEDLINE
DCOM- 20240315
LR  - 20240315
IS  - 1097-4652 (Electronic)
IS  - 0021-9541 (Linking)
VI  - 239
IP  - 3
DP  - 2024 Mar
TI  - Novel targets of beta-TrCP cooperatively accelerate carbohydrate and fatty acid 
      consumption.
PG  - e31095
LID - 10.1002/jcp.31095 [doi]
AB  - Cellular energy is primarily produced from glucose and fat through glycolysis and 
      fatty acid oxidation (FAO) followed by the tricarboxylic acid cycle in 
      mitochondria; energy homeostasis is carefully maintained via numerous feedback 
      pathways. In this report, we uncovered a new master regulator of carbohydrate and 
      lipid metabolism. When ubiquitin E3 ligase beta-TrCP2 was inducibly knocked out in 
      beta-TrCP1 knockout adult mice, the resulting double knockout mice (DKO) lost fat 
      mass rapidly. Biochemical analyses of the tissues and cells from beta-TrCP2 KO and 
      DKO mice revealed that glycolysis, FAO, and lipolysis were dramatically 
      upregulated. The absence of beta-TrCP2 increased the protein stability of metabolic 
      rate-limiting enzymes including 
      6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase (PFKFB3), adipose 
      triglyceride lipase (ATGL), carnitine palmitoyltransferase 1A (CPT1A), and 
      carnitine/acylcarnitine translocase (CACT). Our data suggest that beta-TrCP is a 
      potential regulator for total energy homeostasis by simultaneously controlling 
      glucose and fatty acid metabolism and that targeting beta-TrCP could be an effective 
      strategy to treat obesity and other metabolic disorders.
CI  - (c) 2023 Wiley Periodicals LLC.
FAU - Joo, Hyun Jeong
AU  - Joo HJ
AD  - Department of Biological Sciences, Sookmyung Women's University, Seoul, Republic 
      of Korea.
AD  - Department of Biomedical Sciences, Florida State University, Tallahassee, 
      Florida, USA.
FAU - D'Alessandro, Matthew
AU  - D'Alessandro M
AD  - Department of Biomedical Sciences, Florida State University, Tallahassee, 
      Florida, USA.
FAU - Oh, Gaeun
AU  - Oh G
AD  - Department of Biological Sciences, Sookmyung Women's University, Seoul, Republic 
      of Korea.
FAU - Han, Sora
AU  - Han S
AD  - Department of Biological Sciences, Sookmyung Women's University, Seoul, Republic 
      of Korea.
FAU - Kim, Woo Jung
AU  - Kim WJ
AD  - Department of Biological Sciences, Sookmyung Women's University, Seoul, Republic 
      of Korea.
FAU - Chung, Ga Eun
AU  - Chung GE
AD  - Department of Biological Sciences, Sookmyung Women's University, Seoul, Republic 
      of Korea.
FAU - Jang, Youjeong
AU  - Jang Y
AD  - Department of Biological Sciences, Sookmyung Women's University, Seoul, Republic 
      of Korea.
FAU - Lee, Jung Bok
AU  - Lee JB
AD  - Department of Biological Sciences, Sookmyung Women's University, Seoul, Republic 
      of Korea.
FAU - Lee, Choogon
AU  - Lee C
AD  - Department of Biomedical Sciences, Florida State University, Tallahassee, 
      Florida, USA.
FAU - Yang, Young
AU  - Yang Y
AUID- ORCID: 0000-0003-4239-0804
AD  - Department of Biological Sciences, Sookmyung Women's University, Seoul, Republic 
      of Korea.
LA  - eng
GR  - R01 GM131283/GM/NIGMS NIH HHS/United States
GR  - R01 GM131283/GM/NIGMS NIH HHS/United States
PT  - Journal Article
DEP - 20230816
PL  - United States
TA  - J Cell Physiol
JT  - Journal of cellular physiology
JID - 0050222
RN  - 0 (beta-Transducin Repeat-Containing Proteins)
RN  - 0 (Fatty Acids)
RN  - IY9XDZ35W2 (Glucose)
RN  - EC 2.3.2.27 (Ubiquitin-Protein Ligases)
RN  - 0 (Btrc protein, mouse)
SB  - IM
MH  - Animals
MH  - Mice
MH  - *beta-Transducin Repeat-Containing Proteins/genetics/metabolism
MH  - *Fatty Acids/metabolism
MH  - Glucose/metabolism
MH  - Glycolysis
MH  - Mice, Knockout
MH  - Ubiquitin-Protein Ligases/metabolism
MH  - *Carbohydrate Metabolism
OTO - NOTNLM
OT  - E3 ligase
OT  - energy homeostasis
OT  - metabolism
OT  - obesity
OT  - ubiquitination
OT  - beta-TrCP
EDAT- 2023/08/16 12:41
MHDA- 2024/03/15 06:43
CRDT- 2023/08/16 07:23
PHST- 2023/06/29 00:00 [revised]
PHST- 2023/03/10 00:00 [received]
PHST- 2023/07/25 00:00 [accepted]
PHST- 2024/03/15 06:43 [medline]
PHST- 2023/08/16 12:41 [pubmed]
PHST- 2023/08/16 07:23 [entrez]
AID - 10.1002/jcp.31095 [doi]
PST - ppublish
SO  - J Cell Physiol. 2024 Mar;239(3):e31095. doi: 10.1002/jcp.31095. Epub 2023 Aug 16.