Date of Award
Master of Science
Jay Whelan, Guoxun Chen
Obesity, defined as having excess adipose tissue, is associated with chronic inflammation. Adipose tissue is made up of many cell types, including preadipocytes and adipocytes. Both preadipocytes and adipocytes express pattern recognition receptors that play important roles in innate immunity. Two families of pattern recognition receptors that have been studied in adipose tissue are Toll-like receptors (TLRs) and NOD-like receptors (NLRs). Activation of TLR2 and TLR4 has been shown to lead to proinflammatory response in adipocytes, which is shown to suppress adipocyte differentiation and stimulate lipolysis, one of the major physiological functions of adipocytes. However, the effects of NOD activation on adipocytes have not been studied. Here, we show that activation of NOD1, but not NOD2, by synthetic ligand, suppresses 3T3-L1 adipocyte differentiation shown through Oil-Red-O stained morphology, lipid accumulation, and attenuated gene expression of transcriptional factors PPAR gamma and C/EBP alpha and adipogenic markers (adiponectin, leptin, SCD, FABP4). Moreover, we show that activation of NOD1 by synthetic ligand C12-iEDAP stimulates lipolysis in 3T3-L1 adipocytes in a time and dose-dependent manner. The effects of C12-iEDAP are attenuated by knockdown of NOD1, demonstrating specificity. Additionally, inhibition of NFkappa B and protein kinase A/hormone sensitive lipase via pharmacological inhibitors attenuate the lipolytic effects of C12-iEDAP. NOD1 activation also suppresses lipid droplet coating protein perilipin expression. Overall, our results suggest that NOD1 represents a novel target for adipose inflammation for obesity treatment and prevention.
Purohit, Jaanki Shamb, "Activation of Nucleotide Binding Oligomerization Domain Containing Protein 1 in 3T3-L1 Adipocytes: Effects on Adipocyte Differentiation and Lipolysis. " Master's Thesis, University of Tennessee, 2013.