Carnitine acetyltransferase (CRAT) expression in macrophages is dispensable for nutrient stress sensing and inflammation

Mol Metab. 2017 Jan 3;6(2):219-225. doi: 10.1016/j.molmet.2016.12.008. eCollection 2017 Feb.

Abstract

Objective: Fatty acid oxidation in macrophages is thought to regulate inflammatory status and insulin-sensitivity. An important unanswered question in this field is whether carnitine acetyl-transferase (CrAT) that regulates fatty acid oxidation and mitochondrial acetyl-CoA balance is required to integrate nutrient stress sensing to inflammatory response in macrophages.

Methods: Mice with myeloid lineage-specific Crat deletion were subjected to several metabolic stressors, including high-fat diet-induced obesity, fasting, and LPS-induced endotoxemia. Their metabolic homeostasis was compared to that of Crat-sufficient littermate controls. Inflammatory potential of Crat-deficient and Crat-sufficient macrophages were measured both in vitro and in vivo.

Results: Our studies revealed that ablation of CrAT in myeloid lineage cells did not impact glucose homeostasis, insulin-action, adipose tissue leukocytosis, and inflammation when animals were confronted with a variety of metabolic stressors, including high-fat diet, fasting, or LPS-induced acute endotoxemia.

Conclusions: These findings demonstrate that unlike muscle cells, substrate switch mechanisms that control macrophage energy metabolism and mitochondrial short-chain acyl-CoA pools during nutrient stress are controlled by pathways that are not solely reliant on CrAT.

Keywords: Adipose tissue; Carnitine acyltransferase; Inflammation; Macrophage.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Acetyl Coenzyme A / metabolism
  • Acyl Coenzyme A / metabolism
  • Adipose Tissue / metabolism
  • Animals
  • Carnitine / metabolism
  • Carnitine O-Acetyltransferase / biosynthesis*
  • Carnitine O-Acetyltransferase / genetics
  • Carnitine O-Acetyltransferase / metabolism
  • Diet, High-Fat
  • Energy Metabolism
  • Fatty Acids / metabolism
  • Female
  • Homeostasis / physiology
  • Inflammation / enzymology
  • Inflammation / metabolism
  • Insulin / metabolism
  • Insulin Resistance / physiology
  • Lipid Metabolism
  • Macrophages / enzymology*
  • Macrophages / metabolism
  • Male
  • Mice
  • Mice, Knockout
  • Mitochondria / enzymology
  • Mitochondria / metabolism
  • Obesity / enzymology
  • Obesity / metabolism
  • Oxidation-Reduction

Substances

  • Acyl Coenzyme A
  • Fatty Acids
  • Insulin
  • Acetyl Coenzyme A
  • Carnitine O-Acetyltransferase
  • Carnitine