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Exp Cell Res. 2017 Jan 1;350(1):147-153. doi: 10.1016/j.yexcr.2016.11.016. Epub 2016 Nov 21.

Caloric restriction ameliorates cardiomyopathy in animal model of diabetes.

Author information

1
Cardiac Research Laboratory, Felsenstein Medical Research Institute, Tel Aviv University, Israel; Leviev Heart Center, Sheba Medical Center, Tel Hashomer, Sackler School of Medicine, Tel Aviv University, Israel.
2
Department of Pharmacology, New York Medical College, Valhalla, NY 10595, USA.
3
Cardiac Research Laboratory, Felsenstein Medical Research Institute, Tel Aviv University, Israel.
4
Leviev Heart Center, Sheba Medical Center, Tel Hashomer, Sackler School of Medicine, Tel Aviv University, Israel.
5
Cardiac Research Laboratory, Felsenstein Medical Research Institute, Tel Aviv University, Israel. Electronic address: hochhaus@post.tau.ac.il.

Abstract

BACKGROUND:

The db/db mouse is an animal model of diabetes in which leptin receptor activity is deficient resulting accelerated cardiomyopathy when exposed to angiotensin (AT). Toll-like receptors 4 and 2 (TLR4, TLR2) are pattern recognition receptors, that recognize pathogen-associated molecular patterns and exacerbate and release inflammatory cytokines. Fetuin A (Fet A) is a fatty acid carrier which affects inflammation and insulin resistance in obese humans and animals through TLRs. The aim of this study was to investigate the effect of caloric restriction (CR) on free fatty acids (FFA) level and the inflammatory response in diabetic cardiomyopathy.

METHODS AND RESULTS:

Left ventricular hypertrophy, increased fibrosis and leukocytes infiltration were observed in db/db AT treated hearts. Serum glucose, FFA, and cholesterol levels were elevated in db/db AT treated mice. Cardiac expression of PPARα increased while AKT phosphorylation was decreased.

CONCLUSIONS:

Cumulatively, CR elevated cardiac PPARα improved the utilization of fatty acids, and reduced myocardial inflammation as seen by reduced levels of Fet A. Thus CR negated cardiomyopathy associated with AT in an animal model of diabetes suggesting that CR is an effective therapeutic approach in the treatment of diabetes and associated cardiomyopathy.

KEYWORDS:

AKT; Caloric restriction; Fetuin-A; Free fatty acids; PPARα; TLR2; TLR4; TNF-α; db/db mice

PMID:
27884680
DOI:
10.1016/j.yexcr.2016.11.016
[Indexed for MEDLINE]

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