Fa(c)t checking: How fatty acids shape metabolism and function of macrophages and dendritic cells

Abstract

In recent years there have been major advances in our understanding of the role of free fatty acids (FAs) and their metabolism in shaping the functional properties of macrophages and DCs. This review presents the most recent insights into how cell intrinsic FA metabolism controls DC and macrophage function, as well as the current evidence of the importance of various exogenous FAs (such as polyunsaturated FAs and their oxidation products—prostaglandins, leukotrienes, and proresolving lipid mediators) in affecting DC and macrophage biology, by modulating their metabolic properties. Finally, we explore whether targeted modulation of FA metabolism of myeloid cells to steer their function could hold promise in therapeutic settings.

Metabolism of tissue macrophages in homeostasis and pathology

“…In summary, different types of metabolites (lipids, glucose, and amino acids), lipid handling processes and the involved signaling factors have been shown to foster diverse features in atheroma macrophages during disease progression or regression. This controversy highlights the need for accurate evaluation of the specific microenvironmental conditions (i.e., lipid type/source, stage of the disease, hypoxic regions) [ 263 ] as well as of the model system used (i.e., ex vivo vs. in vivo, peritoneal and/or aortic macrophages) [ 179 ] when investigating complex diseases such as atherosclerosis.…”

Exploring the Links between Obesity and Psoriasis: A Comprehensive Review

“…Furthermore, macrophage exposure to palmitic acid was associated with chronic low-grade inflammation and increased synthesis of IL-1β and IL-23 [ 95 ]. This phenomenon was related to hexokinase inhibition by palmitic acid and Krebs cycle disruption in TLR-activated cells, leading to increased mitochondrial ROS production and pro-inflammatory cytokines.…”

“…Probiotics have been demonstrated to improve psoriasis by modulating the two main parameters of gut microbiota: Alpha and Beta diversity [ 137 ], putting down roots in the quasi-causal role of dysbiosis in the psoriasis pathogenesis in people with obesity. Furthermore, several by-products from gut microbiota metabolism interfere in IL-17 and IL-23 [ 138 ] signalling pathways, whereby microbiota modulates keratinocytes and immune cells [ 95 ]. Thus, probiotic administration in psoriasis improves the clinical manifestation of the disease.…”

Live‐Cell Imaging of Sterculic Acid—a Naturally Occurring 1,2‐Cyclopropene Fatty Acid—by Bioorthogonal Reaction with Turn‐On Tetrazine‐Fluorophore Conjugates**

“…We were particularly interested in whether the levels of lipidated proteins changed upon stimulation of the DCs by LPS, as this could potentially offer mechanistic insights into how DCs can employ changes in fatty acid uptake to alter their immunological function. [68,69] We therefore performed chemical proteomics (Figure 5) and SDS-PAGE (Figure S12) analysis of "resting" and LPSactivated DCs after labelling with 1. For the chemical proteomics, the labelled cells were treated with biotin-PEG4-tetrazine and subjected to streptavidin pull-down, onbead digestion with trypsin and identification by LC-MS/ MS. From the MS data, in total 178 proteins were identified as significantly sterculic acid enriched (Figure 5).…”