PNAs: Research explaining how obesity causes disease

July 25, 2018 / bioin / - adipose tissue macrophages (ATMS) can change their metabolic form to maintain the homeostasis of fat free tissue or lead to inflammation and insulin tolerance in obese patients However, the researchers have not known the factors that control the phenotype polarization and bioenergy of ATM in adipose tissue microenvironment Source: Dan Addison, University of Virginia Communications Recently, scientists from the University of Virginia School of medicine and other units used extracellular flux analysis to find that the metabolism of ATMs isolated from fat poor mice was inhibited Although the research team had previously found that oxyphosphatidylcholine (oxpl) can specifically regulate gene expression and cell metabolism in MOX megaphagocytes, the MOX phenotype of ATMs has not been reported The researchers found a group of unique cx3cr1neg / F4 / 80low ATMs similar to MOX (txnrd1 + HO1 +) phenotype, which is the main ATM phenotype in lean tissue On the contrary, ATMs isolated from obese mice have the typical characteristics of M1 / m2 (CD11c + cd206 +) macrophages, which are highly activated The researchers used targeted liquid chromatography-mass spectrometry to quantify the oxpl types of stromal vessels in mouse adipose tissue The results showed that the expansion of adipose tissue induced by high-fat diet resulted in the increase of total length and broken oxpl mismatch In vitro experiments showed that macrophages respond to broken oxpl by inhibiting bioenergy and up regulating antioxidant pathway, which is similar to ATMs in lean mice, while full-length oxpl can induce the expression of macrophage pro-inflammatory genes and activation of bioenergy state, which is similar to ATMs isolated in obese mice These data identify a reduced regulatory MOX macrophage phenotype that is primarily present in adipose poor tissues, and also indicate that different oxpl enriched in adipose tissue can guide ATMs to change their phenotype and bioenergy status in order to maintain reduced homeostasis or promote inflammation Reference materials: Vlad serbulea et al, macrophage cryptotype and bioenergetics are controlled by oxidised phospholipids identified in lean and obese adpose tissue, Proceedings of the National Academy of Sciences (2018) Doi: 10.1073/pnas.1800544115