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Obestatin and its fragment analog Nt8U were shown to upregulate glycerolipid metabolism and PPARg signalling and decrease fat accumulation in Swiss albino mice(1). 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(2,3). We also wanted to investigate if upregulation of PPARg signalling was a secondary effect of enhanced glycerolipid metabolism. To investigate the same, we administered obestatin pair-wise 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(4). The antagonists also show 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 (5).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.1. Nagaraj S, Raghavan AV, Rao SN, Manjappara UV. Obestatin and Nt8U influence glycerolipid metabolism and PPAR gamma signaling in mice. Int J Biochem Cell Biol. 2014, Aug;53:414-422.2. Musunuru Suneel Kumar Reddy and Uma V Manjappara. Capsaicin but not Genistein Influences Modulation of Lipid Parameters by Obestatin in DIO-C57BL/6 Mice. Int J Pept Res Ther. 2020, 26, 11–19.3. Govardhan Singh R. S, Uma V Manjappara. Impromptu Effects of Nt8U with Soyasaponins on Obesity-related Lipid Parameters in High Fat Fed C57BL/6 Mice. Int J Pept Res Ther. 2020, 26, 405-411.4. Mallikarjuna BG and Manjappara UV. Co-administration with Obestatin Reduces Accumulation of Subcutaneous Fat Due to Rosiglitazone Administration in DIOC57BL/6 Mice. Int J Pept Res Ther. 2020 DOI 10.1007/s10989-020-10028-4.5. Thesis title  “Insights into the mode of action of obestatin: the role of PPARg”, Mallikarjuna BG, 2020, CFTRI, Mysore. Guide : Dr. Uma V. Manjappara.

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