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



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 bothin vitroandin vivo.



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.



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.
Section of Comparative Medicine, Yale School of Medicine, New Haven, CT, USA; Department of Immunobiology, Yale School of Medicine, New Haven, CT, USA.
Emily L
EL
Goldberg
Section of Comparative Medicine, Yale School of Medicine, New Haven, CT, USA; Department of Immunobiology, Yale School of Medicine, New Haven, CT, USA. Electronic address: Vishwa.Dixit@yale.edu.
Vishwa Deep
VD
Dixit
D000105:Acetyl Coenzyme A / Q000378:metabolism; D000214:Acyl Coenzyme A / Q000378:metabolism; D000273:Adipose Tissue / Q000378:metabolism; D000818:Animals; D002331:Carnitine / Q000378:metabolism; D002332:Carnitine O-Acetyltransferase / Q000096:biosynthesis* / Q000235:genetics / Q000378:metabolism; D059305:Diet, High-Fat; D004734:Energy Metabolism; D005227:Fatty Acids / Q000378:metabolism; D005260:Female; D006706:Homeostasis / Q000502:physiology; D007249:Inflammation / Q000201:enzymology / Q000378:metabolism; D007328:Insulin / Q000378:metabolism; D007333:Insulin Resistance / Q000502:physiology; D050356:Lipid Metabolism; D008264:Macrophages / Q000201:enzymology* / Q000378:metabolism; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D008928:Mitochondria / Q000201:enzymology / Q000378:metabolism; D009765:Obesity / Q000201:enzymology / Q000378:metabolism; D010084:Oxidation-Reduction
D000214:Acyl Coenzyme A; D005227:Fatty Acids; D007328:Insulin; D000105:Acetyl Coenzyme A; D002332:Carnitine O-Acetyltransferase; D002331:Carnitine
Adipose tissue; Carnitine acyltransferase; Inflammation; Macrophage