Effect of GW9662 and T0070907 Antagonist of PPARg and Their Coadministration Pairwise with Obestatin on Lipid Profile of DIO-C57BL/6 Mice

Abstract

Obestatin and its fragment analog Nt8U were shown to upregulate glycerolipid metabolism and PPARg signaling and decrease fat accumulation in Swiss albino mice. It was further investigated if these peptides could decrease lipid accumulation under obese conditions. We chose to work on Diet-Induced-Obese (DIO) C57BL/6 mice to study the same. Both obestatin and Nt8U decreased lipid accumulation in DIO-C57BL/6 mice. PPARg was not upregulated in comparison to 60% high-fat diet (HFD) fed control mice, implying there was already enhanced PPARg expression due to HFD consumption. We also wanted to investigate if upregulation of PPARg signaling was a secondary effect of enhanced glycerolipid metabolism. To investigate the same, we administered obestatin pairwise with 2 agonists and 2 antagonists of PPARg. The results revealed obestatin is not a mere agonist of PPARg but can also decrease lipid accumulation brought about by rosiglitazone, a well-studied agonist of PPARg. The antagonists also show a further decrease in lipid accumulation, probably due to inhibition of PPARg activity brought about by HFD and the additive decrease brought about by obestatin in DIO-C57BL/6 mice. This chapter will be structured to briefly introduce obestatin, Nt8U, their effect on gene expression in the adipose tissue, and the effect of PPARg agonists and antagonists on their ability to reduce fat accumulation.