Metabolic diseases, such as obesity, diabetes and atherosclerosis, are the diseases with the highest morbidity and mortality worldwide. Disorders of extracellular microenvironmental signals in macrophages, such as inflammation, oxidative stress, and overnutrition, can induce dysfunction of macrophages and other surrounding cells, thereby promoting the occurrence and development of metabolic diseases. Previous studies have found that the exposure of oleate, a main fatty acid in food and humans, induced macrophage lipid accumulation by inhibiting PPAR signaling (Cell Death & Disease, 2019; Journal Of Cellular And Molecular Medicine, 2019). However, the relevant metabolic changes in the extracellular microenvironment of macrophages still remain unclear.

Oleate was employed to trigger metabolic disturbances in the extracellular microenvironment of macrophages related to the lipid accumulation followed by the intervention with resveratrol and pioglitazone (an anti-diabetic drug), which was conducted by researchers from the research group on Environmental Health and Molecular Toxicology (Qiansheng Huang’s group), Institute of Urban Environment, Chinese Academy of Sciences. GC-MS based metabolomics revealed that multiple metabolic pathways were significantly altered in the extracellular microenvironment of macrophages, and most of above changes were attenuated or abolished by both resveratrol and pioglitazone. Notably, oleate exposure induced significant increases in levels of most saccharides, lactate, isoleucine, degradation products of branched-chain amino acids, myristate and oleate in the extracellular microenvironment of macrophages. Furthermore, the accumulation of fructose, lactate, isoleucine and degradation products of branched-chain amino acids in the extracellular microenvironment of macrophages could be effectively abolished by resveratrol and/or pioglitazone. Above data indicated that carbohydrate metabolism, glycolysis, branched-chain amino acid metabolism and fatty acid metabolism could be used as potential targets for treating metabolic diseases and the intervention with resveratrol and pioglitazone.

This study entitled “Metabolomic characterization of metabolic disturbances in the extracellular microenvironment of oleate-treated macrophages using gas chromatography–mass spectrometry” was published in Analytical Letters, 2020. Dr. Guozhu Ye from Institute of Urban Environment is the first and corresponding author, meanwhile, Dr. Bi-cheng Yang from Jiangxi Provincial Maternal and Child Health Hospitalis is the co-corresponding author. This study was supported by the National Natural Science Foundation of China, the Natural Science Foundation of Fujian Province, the Superior Scientific and Technological Innovation Team of Jiangxi Province and other fundings.

Schematic diagram of metabolic disturbances in the extracellular microenvironment of macrophages induced by oleate exposure.