Premium
L‐4F Improves Metabolic Syndrome Phenotype in HO‐2 Null Mice by Decreasing NFkB Activity & Increasing Adiponectin Levels
Author(s) -
Palladino Leah Marie,
Burgess Angela,
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.1035.5
Subject(s) - medicine , endocrinology , adiponectin , oxidative stress , metabolic syndrome , insulin resistance , inflammation , chemistry , insulin , obesity
We hypothesized that L‐4F, an apoA‐I mimetic peptide, may reduce adiposity and oxidative stress in mice lacking heme oxygenase 2 (HO‐2), which display the metabolic syndrome, leading to the amelioration of insulin resistance. Mice were divided into four groups: Wild‐type (WT) vehicle treated, WT treated with L‐4F (I.P., 2mg/kg daily), HO‐2 null vehicle treated, HO‐2 null treated with L‐4F. In null mice there was limited weight gain, decreased visceral and subcutaneous fat content, decreased plasma TNFα and IL‐6 levels, and increased insulin sensitivity compared to WT controls. We further examined the effect of L‐4F on inflammation by measuring levels of NFκB activity through measurement of p65 and IκBα. The levels of p65 remained the same in both the control and HO‐2 null mice, but there were increased levels of phosphorylated p65 in the nucleus which was reversed in the mice treated with L‐4F. IκBα levels were decreased in HO‐2 knockout mice, but levels were restored with L‐4F treatment implying decreased NFκB activity. In addition, L‐4F treatment increased aortic HO activity and decreased aortic dysfunction. The decrease in adiposity by L‐4F treatment was associated with an increase in serum adiponectin levels. The action of L‐4F decreasing adiposity and increasing insulin sensitivity in an oxidative stress model of metabolic syndrome suggests that L‐4F offers promise in the management of the metabolic syndrome.