Apo A1 Mimetic Rescues the Diabetic Phenotype of HO-2 Knockout Mice via an Increase in HO-1 Adiponectin and LKBI Signaling Pathway.

International Journal of Hypertension
Jian CaoAttallah Kappas

Abstract

Insulin resistance, with adipose tissue dysfunction, is one of the hallmarks of metabolic syndrome. We have reported a metabolic syndrome-like phenotype in heme oxygenase (HO)-2 knockout mice, which presented with concurrent HO-1 deficiency and were amenable to rescue by an EET analog. Apo A-I mimetic peptides, such as L-4F, have been shown to induce HO-1 expression and decrease oxidative stress and adiposity. In this study we aimed to characterize alleviatory effects of HO-1 induction (if any) on metabolic imbalance observed in HO-2 KO mice. In this regard, HO-2((-/-)) mice were injected with 2 mg/kg/day L-4F, or vehicle, i.p., for 6 weeks. As before, compared to WT animals, the HO-2 null mice were obese, displayed insulin resistance, and had elevated blood pressure. These changes were accompanied by enhanced tissue (hepatic) oxidative stress along with attenuation of HO-1 expression and activity and reduced adiponectin, pAMPK, and LKB1 expression. Treatment with L-4F restored HO-1 expression and activity and increased adiponectin, LKB1, and pAMPK in the HO-2((-/-)) mice. These alterations resulted in a decrease in blood pressure, insulin resistance, blood glucose, and adiposity. Taken together, our results show that a deficie...Continue Reading

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Citations

Aug 12, 2014·BioMed Research International·Ersilia NigroAurora Daniele
Aug 6, 2020·International Journal of Molecular Sciences·Christiaan M SuttorpFrank A D T G Wagener
Oct 25, 2017·Journal of Nutrition and Metabolism·Nitin PuriStephen J Peterson
Sep 26, 2020·Frontiers in Cell and Developmental Biology·Nanne VerheijenFrank A D T G Wagener
Aug 20, 2019·Archives of Biochemistry and Biophysics·George S DrummondNader G Abraham
Jan 1, 2021·Biomedicine & Pharmacotherapy = Biomédecine & Pharmacothérapie·Subhojit PaulYasmin Ahmad

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Methods Mentioned

BETA
protein assay
PCR

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