C333H, a novel PPARα/γ dual agonist, has beneficial effects on insulin resistance and lipid metabolism
Abstract
Aim: To examine the effects of novel peroxisome proliferator-activated receptor
(PPAR) α/γ dual agonist C333H on insulin resistance and lipid metabolism.
Methods: An established dual-luciferase reporter gene assay system was used in
vitro to test the activity of C333H with respect to the transcription of human
PPARα and PPARγ. A preadipocyte differentiation assay and reverse transcription-
polymerase chain reaction were used to detect the functional activities of
C333H. In db/db mice, the effects of C333H were investigated with respect to
lowering of blood glucose and lipid levels. Results: C333H was determined to be
a novel PPARα/γ dual agonist because it strongly induced luciferase activity on
human PPARα and PPARγ, promoting the differentiation of preadipocytes to
adipocytes, and functioning in upregulating the expression of some glucose and
lipid metabolic target genes of the PPAR. In addition, C333H efficiently reduced
blood lipid and glucose concentrations in db/db diabetic mice. Conclusion: C333H
has dual action on both PPARα and PPARγ, and might be of interest for the
amelioration of lipid metabolic disorders and insulin resistance associated with
type 2 diabetes.
Keywords:
(PPAR) α/γ dual agonist C333H on insulin resistance and lipid metabolism.
Methods: An established dual-luciferase reporter gene assay system was used in
vitro to test the activity of C333H with respect to the transcription of human
PPARα and PPARγ. A preadipocyte differentiation assay and reverse transcription-
polymerase chain reaction were used to detect the functional activities of
C333H. In db/db mice, the effects of C333H were investigated with respect to
lowering of blood glucose and lipid levels. Results: C333H was determined to be
a novel PPARα/γ dual agonist because it strongly induced luciferase activity on
human PPARα and PPARγ, promoting the differentiation of preadipocytes to
adipocytes, and functioning in upregulating the expression of some glucose and
lipid metabolic target genes of the PPAR. In addition, C333H efficiently reduced
blood lipid and glucose concentrations in db/db diabetic mice. Conclusion: C333H
has dual action on both PPARα and PPARγ, and might be of interest for the
amelioration of lipid metabolic disorders and insulin resistance associated with
type 2 diabetes.