Acetyl-CoA Carboxylase 1 is a Suppressor of the Adipocyte Thermogenic Program

Overview

Journal Cell Rep

Publisher Cell Press

Specialties Biology
Cell Biology
Molecular Biology

Date 2023 May 10

PMID 37163372

Authors

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

Affiliations

Soon will be listed here.

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.

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