Fmoc-L-Leucine

Peroxisome proliferator-activated receptor ? (PPAR?) isoforms heterodimerize with retinoic X receptors to modulate gene expression related to adipocyte differentiation, fatty acid uptake and storage, and glucose metabolism.{18294} Natural agonists of PPAR? include fatty acids (e.g., linoleic acid and 15-deoxy-?12,14-prostaglandin J2), while thiazolidinediones (e.g., rosiglitazone and pioglitazone) are potent synthetic agonists.{18295,18296} Fmoc-L-leucine is a partial agonist of PPAR?.{18295,11781} It activates PPAR? with a lower potency (Ki = 15 versus 0.035 µM) but a similar maximal efficacy compared to rosiglitazone.{11781} Fmoc-L-leucine improves insulin resistance in normal, diet-induced glucose-intolerant and in diabetic db/db mice, yet has reduced adipogenic activity.{11781} As a result, it is classified as a selective PPAR? modulator (SPPARM), capable of producing insulin-sensitizing effects while minimizing side effects associated with full agonists.{18295}