PMID- 37561578
OWN - NLM
STAT- MEDLINE
DCOM- 20230926
LR  - 20240210
IS  - 2379-3708 (Electronic)
IS  - 2379-3708 (Linking)
VI  - 8
IP  - 18
DP  - 2023 Sep 22
TI  - ACOT1 deficiency attenuates high-fat diet-induced fat mass gain by increasing 
      energy expenditure.
LID - 10.1172/jci.insight.160987 [doi]
LID - e160987
AB  - Acyl-CoA thioesterase 1 (ACOT1) catalyzes the hydrolysis of long-chain acyl-CoAs 
      to free fatty acids and CoA and is typically upregulated in obesity. Whether 
      targeting ACOT1 in the setting of high-fat diet-induced (HFD-induced) obesity 
      would be metabolically beneficial is not known. Here we report that male and 
      female ACOT1KO mice are partially protected from HFD-induced obesity, an effect 
      associated with increased energy expenditure without alterations in physical 
      activity or food intake. In males, ACOT1 deficiency increased mitochondrial 
      uncoupling protein-2 (UCP2) protein abundance while reducing 4-hydroxynonenal, a 
      marker of oxidative stress, in white adipose tissue and liver of HFD-fed mice. 
      Moreover, concurrent knockdown (KD) of UCP2 with ACOT1 in hepatocytes prevented 
      increases in oxygen consumption observed with ACOT1 KD during high lipid loading, 
      suggesting that UCP2-induced uncoupling may increase energy expenditure to 
      attenuate weight gain. Together, these data indicate that targeting ACOT1 may be 
      effective for obesity prevention during caloric excess by increasing energy 
      expenditure.
FAU - Heden, Timothy D
AU  - Heden TD
AD  - Pennington Biomedical Research Center, Baton Rouge, Louisiana, USA.
FAU - Franklin, Mallory P
AU  - Franklin MP
AD  - Department of Biochemistry, Molecular Biology and Biophysics and.
FAU - Dailey, Christina
AU  - Dailey C
AD  - Department of Biochemistry, Molecular Biology and Biophysics and.
FAU - Mashek, Mara T
AU  - Mashek MT
AD  - Department of Biochemistry, Molecular Biology and Biophysics and.
FAU - Chen, Chen
AU  - Chen C
AD  - Department of Biochemistry, Molecular Biology and Biophysics and.
FAU - Mashek, Douglas G
AU  - Mashek DG
AD  - Department of Biochemistry, Molecular Biology and Biophysics and.
AD  - Department of Medicine, Division of Diabetes, Endocrinology and Metabolism, 
      Medical School, University of Minnesota, Minneapolis, Minnesota, USA.
LA  - eng
GR  - R01 DK114401/DK/NIDDK NIH HHS/United States
GR  - R01 AG055452/AG/NIA NIH HHS/United States
GR  - F32 DK109556/DK/NIDDK NIH HHS/United States
GR  - P20 GM135002/GM/NIGMS NIH HHS/United States
GR  - L30 DK110338/DK/NIDDK NIH HHS/United States
GR  - T32 DK083250/DK/NIDDK NIH HHS/United States
GR  - R01 DK108790/DK/NIDDK NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20230922
PL  - United States
TA  - JCI Insight
JT  - JCI insight
JID - 101676073
SB  - IM
MH  - Animals
MH  - Female
MH  - Male
MH  - Mice
MH  - *Diet, High-Fat
MH  - Energy Metabolism
MH  - Liver/metabolism
MH  - *Obesity/metabolism
MH  - Weight Gain
PMC - PMC10561717
OTO - NOTNLM
OT  - Fatty acid oxidation
OT  - Metabolism
OT  - Obesity
OT  - Uncoupling proteins
COIS- Conflict of interest: The authors have declared that no conflict of interest 
      exists.
EDAT- 2023/08/10 18:42
MHDA- 2023/09/25 06:43
PMCR- 2023/09/22
CRDT- 2023/08/10 12:03
PHST- 2022/04/13 00:00 [received]
PHST- 2023/08/08 00:00 [accepted]
PHST- 2023/09/25 06:43 [medline]
PHST- 2023/08/10 18:42 [pubmed]
PHST- 2023/08/10 12:03 [entrez]
PHST- 2023/09/22 00:00 [pmc-release]
AID - 160987 [pii]
AID - 10.1172/jci.insight.160987 [doi]
PST - epublish
SO  - JCI Insight. 2023 Sep 22;8(18):e160987. doi: 10.1172/jci.insight.160987.