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Acetyl-CoA carboxylase 1 is a suppressor of the adipocyte thermogenic program
A. Guilherme, LA. Rowland, N. Wetoska, E. Tsagkaraki, KB. Santos, AH. Bedard, F. Henriques, M. Kelly, S. Munroe, DJ. Pedersen, OR. Ilkayeva, TR. Koves, L. Tauer, M. Pan, X. Han, JK. Kim, CB. Newgard, DM. Muoio, MP. Czech
Jazyk angličtina Země Spojené státy americké
Typ dokumentu časopisecké články, Research Support, N.I.H., Extramural
Grantová podpora
R01 DK116056
NIDDK NIH HHS - United States
R01 DK089312
NIDDK NIH HHS - United States
R37 DK030898
NIDDK NIH HHS - United States
U2C DK093000
NIDDK NIH HHS - United States
R01 DK121710
NIDDK NIH HHS - United States
R01 DK103047
NIDDK NIH HHS - United States
R01 DK030898
NIDDK NIH HHS - United States
P30 DK124723
NIDDK NIH HHS - United States
NLK
Cell Press Free Archives
od 2012
Directory of Open Access Journals
od 2012
Free Medical Journals
od 2012
Freely Accessible Science Journals
od 2012-01-26
Open Access Digital Library
od 2012-01-01
Open Access Digital Library
od 2012-01-26
- MeSH
- acetyl-CoA-karboxylasa * metabolismus MeSH
- acetylkoenzym A metabolismus MeSH
- myši knockoutované MeSH
- myši MeSH
- palmitany metabolismus MeSH
- syntázy mastných kyselin metabolismus MeSH
- termogeneze MeSH
- tukové buňky * metabolismus MeSH
- zvířata MeSH
- Check Tag
- myši MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- Research Support, N.I.H., Extramural MeSH
Disruption of adipocyte de novo lipogenesis (DNL) by deletion of fatty acid synthase (FASN) in mice induces browning in inguinal white adipose tissue (iWAT). However, adipocyte FASN knockout (KO) increases acetyl-coenzyme A (CoA) and malonyl-CoA in addition to depletion of palmitate. We explore which of these metabolite changes triggers adipose browning by generating eight adipose-selective KO mouse models with loss of ATP-citrate lyase (ACLY), acetyl-CoA carboxylase 1 (ACC1), ACC2, malonyl-CoA decarboxylase (MCD) or FASN, or dual KOs ACLY/FASN, ACC1/FASN, and ACC2/FASN. Preventing elevation of acetyl-CoA and malonyl-CoA by depletion of adipocyte ACLY or ACC1 in combination with FASN KO does not block the browning of iWAT. Conversely, elevating malonyl-CoA levels in MCD KO mice does not induce browning. Strikingly, adipose ACC1 KO induces a strong iWAT thermogenic response similar to FASN KO while also blocking malonyl-CoA and palmitate synthesis. Thus, ACC1 and FASN are strong suppressors of adipocyte thermogenesis through promoting lipid synthesis rather than modulating the DNL intermediates acetyl-CoA or malonyl-CoA.
Department of Medicine Duke University School of Medicine Durham NC 27705 USA
Program in Molecular Medicine University of Massachusetts Chan Medical School Worcester MA 01605 USA
Citace poskytuje Crossref.org
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- $a Disruption of adipocyte de novo lipogenesis (DNL) by deletion of fatty acid synthase (FASN) in mice induces browning in inguinal white adipose tissue (iWAT). However, adipocyte FASN knockout (KO) increases acetyl-coenzyme A (CoA) and malonyl-CoA in addition to depletion of palmitate. We explore which of these metabolite changes triggers adipose browning by generating eight adipose-selective KO mouse models with loss of ATP-citrate lyase (ACLY), acetyl-CoA carboxylase 1 (ACC1), ACC2, malonyl-CoA decarboxylase (MCD) or FASN, or dual KOs ACLY/FASN, ACC1/FASN, and ACC2/FASN. Preventing elevation of acetyl-CoA and malonyl-CoA by depletion of adipocyte ACLY or ACC1 in combination with FASN KO does not block the browning of iWAT. Conversely, elevating malonyl-CoA levels in MCD KO mice does not induce browning. Strikingly, adipose ACC1 KO induces a strong iWAT thermogenic response similar to FASN KO while also blocking malonyl-CoA and palmitate synthesis. Thus, ACC1 and FASN are strong suppressors of adipocyte thermogenesis through promoting lipid synthesis rather than modulating the DNL intermediates acetyl-CoA or malonyl-CoA.
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