Adipose Tissue Derived Free Fatty Acids Initiate Myeloid Cell Accumulation in Mouse Liver in States of Lipid Oversupply.

TitleAdipose Tissue Derived Free Fatty Acids Initiate Myeloid Cell Accumulation in Mouse Liver in States of Lipid Oversupply.
Publication TypeJournal Article
Year of Publication2018
AuthorsDB H, C WU, N D, IJ S, M S-R, G S, CP O'D, LC A, EE K, EE K, RM O'D
JournalAm J Physiol Endocrinol Metab
Date Published08/2018
Keywordsadipose tissue; dendritic cells; free fatty acids; inflammation; liver; monocytes
Abstract

Accumulation of myeloid cells in the liver, notably dendritic cells (DCs) and monocytes/macrophages (MCs), is a major component of the metainflammation of obesity. However, the mechanism(s) stimulating hepatic DC/MC infiltration remain ill defined. Herein, we addressed the hypothesis that adipose tissue (AT) free fatty acids (FFAs) play a central role in the initiation of hepatic DC/MC accumulation, using a number of mouse models of altered FFA supply to the liver. In two models of acute FFA elevation (lipid infusion and fasting) hepatic DC/MC and triglycerides (TGs) but not AT DC/MC were increased without altering plasma cytokines (PCs; TNFα and monocyte chemoattractant protein 1) and with variable effects on oxidative stress (OxS) markers. However, fasting in mice with profoundly reduced AT lipolysis (AT-specific deletion of adipose TG lipase; AAKO) failed to elevate liver DC/MC, TG, or PC, but liver OxS increased. Livers of obese AAKO mice that are known to be resistant to steatosis were similarly protected from inflammation. In high-fat feeding studies of 1, 3, 6, or 20-wk duration, liver DC/MC accumulation dissociated from PC and OxS but tracked with liver TGs. Furthermore, decreasing OxS by ~80% in obese mice failed to decrease liver DC/MC. Therefore, FFA and more specifically AT-derived FFA stimulate hepatic DC/MC accumulation, thus recapitulating the pathology of the obese liver. In a number of cases the effects of FFA can be dissociated from OxS and PC but match well with liver TG, a marker of FFA oversupply.

DOI10.1152/ajpendo.00172.2018