Premium
L‐4F Rescues the Metabolic Syndrome Phenotype of HO‐2 Null Mice via Insulin, Adiponectin, & LKB1 Signaling Pathways
Author(s) -
Angevine Kristine Rose,
Burgess Angela P,
Vanella Luca,
Kim Dong Hyun,
Sodhi Komal,
Peterson Stephen J,
Abraham Nader G,
MensahOsman Edith
Publication year - 2010
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.24.1_supplement.570.2
Subject(s) - endocrinology , medicine , adiponectin , metabolic syndrome , insulin resistance , chemistry , oxidative stress , insulin , biology , obesity
The development of apoA‐I mimetic peptides, such as 4F, has been shown to decrease ROS and adiposity. Studies suggest that CYP‐derived epoxyeicosatrienoic acids (EETs) decrease adiposity and participate in vascular protection. We hypothesized that the apolipoprotein mimetic peptide, L‐4F, may reduce adiposity and oxidative stress in mice lacking heme oxygenase‐2 genes, which displays obesity and metabolic syndrome via an increase in EET synthesis. Wild type and HO‐2 −/− Mice were divided into three groups: Vehicle treated, L4‐F treated, and L4‐F + SnMP (antagonist to HO‐1), and injected with 2mg/kg via IP daily for 8 weeks. L‐4F‐mediated increases in EETs levels were associated with increases in adiponectin, pLKB‐1, pAMPK and NO levels in HO‐2 −/− mice. Suppression of HO activity by administration of SnMP to L4‐F‐treated HO‐2 −/− mice reverses adiposity and decreases adiponectin levels. The anti‐obesity effects of L‐4F are manifested by a decrease in visceral fat content with reciprocal increases in adiponectin, LKB‐1 and pAMPK. The increase in adiponectin, LKB‐1 and pAMPK resulted in restoration of vascular dysfunction as seen by a decrease in adiposity and improved insulin sensitivity, suggesting the L4‐F may have beneficial effects on obesity, diabetes, and atherosclerosis.