Apo A1 Mimetic Rescues the Diabetic Phenotype of HO-2 Knockout Mice via an Increase in HO-1 Adiponectin and LKBI Signaling Pathway
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 mimet...
Main Authors: | , , , , , |
---|---|
Format: | Article |
Language: | English |
Published: |
Hindawi Limited
2012-01-01
|
Series: | International Journal of Hypertension |
Online Access: | http://dx.doi.org/10.1155/2012/628147 |
id |
doaj-301a8d87b3d54c71b4ca9045d96484d2 |
---|---|
record_format |
Article |
spelling |
doaj-301a8d87b3d54c71b4ca9045d96484d22020-11-24T23:46:54ZengHindawi LimitedInternational Journal of Hypertension2090-03842090-03922012-01-01201210.1155/2012/628147628147Apo A1 Mimetic Rescues the Diabetic Phenotype of HO-2 Knockout Mice via an Increase in HO-1 Adiponectin and LKBI Signaling PathwayJian Cao0Nitin Puri1Komal Sodhi2Lars Bellner3Nader G. Abraham4Attallah Kappas5Department of Geriatric Cardiology, Chinese PLA General Hospital, Beijing 100853, ChinaDepartment of Physiology and Pharmacology, College of Medicine, University of Toledo, Toledo, OH 43614, USADepartment of Physiology and Pharmacology, College of Medicine, University of Toledo, Toledo, OH 43614, USADepartment of Pharmacology, New York Medical College, Valhalla, NY 10595, USADepartment of Physiology and Pharmacology, College of Medicine, University of Toledo, Toledo, OH 43614, USAThe Rockefeller University, New York, NY 10065, USAInsulin 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 deficient HO-1 response, in a state with reduced HO-2 basal levels, is accompanied by disruption of metabolic homeostasis which is successfully restored by an HO-1 inducer.http://dx.doi.org/10.1155/2012/628147 |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Jian Cao Nitin Puri Komal Sodhi Lars Bellner Nader G. Abraham Attallah Kappas |
spellingShingle |
Jian Cao Nitin Puri Komal Sodhi Lars Bellner Nader G. Abraham Attallah Kappas 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 |
author_facet |
Jian Cao Nitin Puri Komal Sodhi Lars Bellner Nader G. Abraham Attallah Kappas |
author_sort |
Jian Cao |
title |
Apo A1 Mimetic Rescues the Diabetic Phenotype of HO-2 Knockout Mice via an Increase in HO-1 Adiponectin and LKBI Signaling Pathway |
title_short |
Apo A1 Mimetic Rescues the Diabetic Phenotype of HO-2 Knockout Mice via an Increase in HO-1 Adiponectin and LKBI Signaling Pathway |
title_full |
Apo A1 Mimetic Rescues the Diabetic Phenotype of HO-2 Knockout Mice via an Increase in HO-1 Adiponectin and LKBI Signaling Pathway |
title_fullStr |
Apo A1 Mimetic Rescues the Diabetic Phenotype of HO-2 Knockout Mice via an Increase in HO-1 Adiponectin and LKBI Signaling Pathway |
title_full_unstemmed |
Apo A1 Mimetic Rescues the Diabetic Phenotype of HO-2 Knockout Mice via an Increase in HO-1 Adiponectin and LKBI Signaling Pathway |
title_sort |
apo a1 mimetic rescues the diabetic phenotype of ho-2 knockout mice via an increase in ho-1 adiponectin and lkbi signaling pathway |
publisher |
Hindawi Limited |
series |
International Journal of Hypertension |
issn |
2090-0384 2090-0392 |
publishDate |
2012-01-01 |
description |
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 deficient HO-1 response, in a state with reduced HO-2 basal levels, is accompanied by disruption of metabolic homeostasis which is successfully restored by an HO-1 inducer. |
url |
http://dx.doi.org/10.1155/2012/628147 |
work_keys_str_mv |
AT jiancao apoa1mimeticrescuesthediabeticphenotypeofho2knockoutmiceviaanincreaseinho1adiponectinandlkbisignalingpathway AT nitinpuri apoa1mimeticrescuesthediabeticphenotypeofho2knockoutmiceviaanincreaseinho1adiponectinandlkbisignalingpathway AT komalsodhi apoa1mimeticrescuesthediabeticphenotypeofho2knockoutmiceviaanincreaseinho1adiponectinandlkbisignalingpathway AT larsbellner apoa1mimeticrescuesthediabeticphenotypeofho2knockoutmiceviaanincreaseinho1adiponectinandlkbisignalingpathway AT nadergabraham apoa1mimeticrescuesthediabeticphenotypeofho2knockoutmiceviaanincreaseinho1adiponectinandlkbisignalingpathway AT attallahkappas apoa1mimeticrescuesthediabeticphenotypeofho2knockoutmiceviaanincreaseinho1adiponectinandlkbisignalingpathway |
_version_ |
1725491782761840640 |