Acetyl-CoA carboxylase 1 is a suppressor of the adipocyte thermogenic program

Adilson Guilherme, Leslie A. Rowland, Nicole Wetoska, Emmanouela Tsagkaraki, Kaltinaitis B. Santos, Alexander H. Bedard, Felipe Henriques, Mark Kelly, Sean Munroe, David J. Pedersen, Olga R. Ilkayeva, Timothy R. Koves, Lauren Tauer, Meixia Pan, Xianlin Han, Jason K. Kim, Christopher B. Newgard, Deborah M. Muoio, Michael P. Czech

Research output: Contribution to journalArticlepeer-review

Abstract

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.

Original languageEnglish (US)
Article number112488
JournalCell Reports
Volume42
Issue number5
DOIs
StatePublished - May 30 2023

Keywords

  • ACC1
  • CP: Metabolism
  • FASN
  • UCP1
  • acetyl-CoA
  • adipose tissue
  • browning
  • fatty acids
  • lipogenesis
  • malonyl-CoA
  • thermogenesis

ASJC Scopus subject areas

  • General Biochemistry, Genetics and Molecular Biology

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