LT175 is a novel PPARalpha/gamma ligand with potent insulin-sensitizing effects and reduced adipogenic properties

Background: PPARs are attractive targets of antidiabetic agents. However, PPAR ligands show side effects that hinder their clinical use. Results: LT175 improves insulin sensitivity and reduces body weight via selective gene activation in adipose tissue. Conclusion: LT175 shows an improved pharmacological profile linked to characteristic binding and differential coregulator recruitment. Significance: LT175 may be a scaffold molecule to design a safer generation of PPAR ligands. © 2014 by The American Society for Biochemistry and Molecular Biology, Inc.