Abstract
The effect of bacterial lipopolysaccharide (LPS) on eukaryotic cell could be accompanied by a significant metabolic shift that includes accumulation of triacylglycerol (TAG) in lipid droplets (LD), ubiquitous organelles associated with fatty acid storage, energy regulation and demonstrated tight spatial and functional connections with mitochondria. The impairment of mitochondrial activity under pathological stimuli has been shown to provoke TAG storage and LD biogenesis. However the potential mechanisms that link mitochondrial disturbances and TAG accumulation are not completely understood. We hypothesize that mitochondrial ROS (mROS) may play a role of a trigger leading to subsequent accumulation of intracellular TAG and LD in response to a bacterial stimulus. Using isolated epithelial cells from the frog urinary bladder, we showed that LPS decreased fatty acids oxidation, enhanced TAG deposition, and promoted LD formation. LPS treatment did not affect the mitochondrial membrane potential but increased cellular ROS production and led to impairment of mitochondrial function as revealed by decreased ATP production and a reduced maximal oxygen consumption rate (OCR) and OCR directed at ATP turnover. The mitochondrial-targeted antioxidant MitoQ at a dose of 25 nM did not prevent LPS-induced alterations in cellular respiration, but, in contrast to nonmitochondrial antioxidant α-tocopherol, reduced the effect of LPS on the generation of ROS, restored the LPS-induced decline of fatty acids oxidation, and prevented accumulation of TAG and LD biogenesis. The data obtained indicate the key signaling role of mROS in the lipid metabolic shift that occurs under the impact of a bacterial pathogen in epithelial cells.
Highlights
Bacterial lipopolysaccharide (LPS), the main membrane component of Gram-negative bacteria, is one of the most important pathogen-associated molecular patterns, which elicits the host innate immune response as well as inflammation
The effect of LPS on eukaryotic cells could be accompanied by a significant metabolic shift including accumulation of triacylglycerol (TAG) deposited in lipid droplets (LD), ubiquitous organelles that are associated with fatty acid storage, energy regulation, and control of bioactive lipid mediator production [1, 2])
The neutral lipid fluorescent dye Nile Red revealed the presence of LD at different quantities in virtually all control Frog urinary bladder epithelial cells LD (FUBEC), nonuniformly distributed in the cytoplasm, sometimes forming aggregates (Figure 1(a))
Summary
Bacterial lipopolysaccharide (LPS), the main membrane component of Gram-negative bacteria, is one of the most important pathogen-associated molecular patterns, which elicits the host innate immune response as well as inflammation. The effect of LPS on eukaryotic cells could be accompanied by a significant metabolic shift including accumulation of triacylglycerol (TAG) deposited in lipid droplets (LD), ubiquitous organelles that are associated with fatty acid storage, energy regulation, and control of bioactive lipid mediator production [1, 2]). Among them are the increase of CD36-mediated uptake of fatty acids and their incorporation into TAG [3, 4], the decrease of adipose triglyceride lipase(ATGL-) mediated TAG lipolysis [4], the impairment of fatty acids oxidation (FAO), and downregulation of expression of the transcriptional factor PPARα and its downstream genes that are required for FAO [7, 8, 11, 12] These effects can be triggered by earlier step(s) in LPS signaling, initiating alterations in the expression and activity of proteins involved in cellular lipid metabolism. With the use of the mitochondrialtargeted antioxidant MitoQ, we tried to demonstrate whether mROS play the trigger role in LPS-induced lipid metabolic shift
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