High fat diet enhances cardiac abnormalities in SHR rats: Protective role of heme oxygenase-adiponectin axis
Authors: Sumit R Monu
Komal Sodhi
Nitin Puri
Jian Cao
Rita Rezzani
Nader G Abraham
Journal: Diabetology & Metabolic Syndrome (2011)
Discipline: CLINICAL MEDICINE
Keywords: dietary fat intake; cardiovascular structure; metabolic dysfunction; obesity; cardiomyopathy
Affiliations: Department of Geriatric Cardiology, Chinese PLA General Hospital, Beijing 100853, China., Department of Physiology and Pharmacology, College of Medicine, University of Toledo, Toledo, Ohio, 43614, USA., Department of Biomedical Science, Division of Anatomy, University of Brescia, Brescia Italy.

Abstract:  Background: High dietary fat intake is a major risk factor for development of cardiovascular and metabolic dysfunction including obesity, cardiomyopathy and hypertension. Methods: The present study was designed to examine effect of high fat (HF) diet on cardio-vascular structure and function in spontaneously hypertensive rats (SHR), fed HF diet for 15 weeks, a phenotype designed to mimic metabolic syndrome. Results: Development of metabolic syndrome like phenotype was confirmed using parameters, including body weight, total cholesterol and blood pressure levels. High fat diet impaired vascular relaxation by acetylcholine and exacerbated cardiac dysfunction in SHRs as evidenced by lower left ventricular function, and higher coronary resistance (CR) as compared to controls (p &lt; 0.05). The histological examination revealed significant myocardial and peri-vascular fibrosis in hearts from SHRs on HF diet. This cardiac dysfunction was associated with increased levels of inflammatory cytokines, COX-2, NOX-2, TxB2 expression and increase in superoxide (O2-) levels in SHR fed a HF diet (p &lt; 0.05). HO-1 induction via cobalt-protoporphyrin (CoPP,3 mg/kg), in HF fed rats, not only improved cardiac performance parameters, but also prevented myocardial and perivascular fibrosis. These effects of CoPP were accompanied by enhanced levels of cardiac adiponectin levels, pAMPK, peNOS and iNOS expression; otherwise significantly attenuated (p &lt; 0.05) in HF fed SHRs. Prevention of such beneficial effects of CoPP by the concurrent administration of the HO inhibitor stannic mesoporphyrin (SnMP) corroborates the role of HO system in mediating such effects. Conclusion: In conclusion, this novel study demonstrates that up-regulation of HO-1 improves cardiac and vascular dysfunction by blunting oxidative stress, COX-2 levels and increasing adiponectin levels in hypertensive rats on HF diet. 

Retracted: No

PubPeer comments:
 This paper shows the same actin control that appears in two other publications; each paper uses different experimental protocols, different tissues (heart, liver and adipose) and different animals. Diabetology Metabolic Syndrome 2011, 3:37. Figure 8 Western blot and densitometry analysis of adiponectin, AMPK, pAMPK, AKT, pAKT, eNOS, p-eNOS, iNOS proteins in heart from SHRs. This paper used the SHR (spontaneously hypertensive rats) strain from Charles River. PLOS ONE, 2015 Fig 6D. Effect of induction of HO-1 (CoPP) and inhibition of HO (SnMP) in mice fed a high fructose diet for 8 weeks on western blot and densitometry analysis. This paper used mice fed a high fructose diet. Previously commented on: https: pubpeer.com publications 6BF6BCD78CF68B8B1DC710A72C8656 International Journal of Obesity (2014) Figure 6A. Effects of the PPARd-agonist on adipogenic marker expression in adipose tissue in 2K1C animalsu2014treated with and without GW 501516 or GW 501516u00feSnMP This paper used the Goldblatt 2 kidney 1 clip (2K1C) model of hypertension in Sprague Dawley rats. Previously commented on: https: pubpeer.com publications D0737900D02C1DD5D8721FB4B52372 ![file] ,