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The role of the nuclear receptor peroxisome proliferator activated receptor-gamma (PPAR gamma) as a potential target to alter the sepsis-induced inflammatory response. PPAR gamma is a nuclear receptor with effects on lipid and glucose metabolism, atherosclerosis and inflammation. The thiazolidinediones (TZDs), pioglitazone and rosiglitazone, are Food and Drug Administration (FDA)-approved medications that activate PPAR gamma. TZDs are used therapeutically as insulin-sensitizers for patients with type 2 diabetes. In these patients TZDs have favorable effects on modulating the inflammatory response.
The Kaplan laboratory is collaborating with Basilia Zingarelli, MD, PhD to investigate the critical molecular mechanisms involved in the PPAR gamma pathway in sepsis.
Upon ligand binding, PPARg forms a heterodimer with the retinoic acid receptor (RXR). The interaction with the RXR allows the recruitment of a set of cofactors. This complex binds to the PPAR response element (PPRE) in the promoter region of certain target genes to modulate transcription.
A second focus of the laboratory is on the increased susceptibility of diet-induced obesity to sepsis. The Kaplan laboratory focuses on the critical links between the inflammatory pathways in sepsis and obesity and the importance of adipose tissue biology on inflammation.
Representative image of magnetic imaging with 7T MRI demonstrating that mice on a high fat diet have increased adiposity.
Immunohistochemistry of F4/80 macrophage stain of liver sections of normal (A) and high fat (B) chow-fed mice demonstrating hepatic macrophage accumulation. 10x magnification.
PPAR Gamma In Pediatric Sepsis And The Inflammatory Response In ObesityPI: Jennifer KaplanProject Number: 5K08GM093135-02
PPAR Gamma And PPAR Gamma Agonists In Septic ShockPI: Basilia ZingarelliProject Number: 5R01GM067202-08
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