Inhibition of perilipin 2 expression reduces pro-inflammatory gene expression and increases lipid droplet size

• Published in: Food & function 2018-12, Vol.9 (12), p.6245-6256
• Main Authors: Norman, Jennifer E, Aung, Hnin H, Wilson, Dennis W, Rutledge, John C
• Format: Article
• Language: English
• Subjects: adipophilin; Adult; Atherogenesis; blood serum; Chemokine CCL3 - genetics; Chemokine CCL3 - metabolism; DNA microarrays; Down-Regulation; droplet size; Droplets; enzymes; Female; Fibrosarcoma; Gene expression; Glucocorticoids; Homology; Humans; Inflammation; Inhibition; Interleukin 8; Interleukin-8 - genetics; Interleukin-8 - metabolism; Kinases; ligands; Lipid Droplets - chemistry; Lipid Droplets - metabolism; Lipids; Lipolysis; lipoproteins; Lipoproteins - metabolism; Male; microarray technology; Monocytes; Monocytes - drug effects; Monocytes - metabolism; oncogenes; Perilipin-2 - genetics; Perilipin-2 - metabolism; polymerase chain reaction; Reduction; Reverse transcription; siRNA; small interfering RNA; triacylglycerols; Triglycerides - metabolism; Young Adult
• ISSN: 2042-6496; 2042-650X; 2042-650X
• DOI: 10.1039/c8fo01420e

Our lab previously demonstrated that triglyceride-rich lipoprotein (TGRL) lipolysis products induce lipid droplet formation and pro-inflammatory gene expression in monocytes. We hypothesized that the inhibition of perilipin 2 expression in THP-1 monocytes would reduce lipid droplet formation and suppress pro-inflammatory gene expression induced by TGRL lipolysis products. In the current study, we use microarray analysis to identify gene expression altered by TGRL lipolysis products in THP-1 monocytes. We confirmed the expression of selected genes by quantitative reverse transcription PCR and characterized lipid droplet formation in these cells after exposure to TGRL lipolysis products. Using siRNA inhibition of perilipin 2 expression, we examined the role of perilipin 2 in the response of THP-1 monocytes to TGRL lipolysis products. We found that perilipin 2 siRNA increased the intracellular triglyceride content, increased the size of lipid droplets, and reduced pro-atherogenic and pro-inflammatory gene expression. We saw a reduction of serum/glucocorticoid kinase 1, v-maf musculoaponeurotic fibrosarcoma oncogene homolog F (avian), chemokine (C-C motif) ligand 3, and interleukin 8 gene expression induced by TGRL lipolysis products. This study supports previous findings that reduction of perilipin 2 expression is protective against atherogenesis, while finding an unexpected increase in lipid droplet size with reduced perilipin 2 expression.