Supplementation with a Carob (Ceratonia siliqua L.) Fruit Extract Attenuates the Cardiometabolic Alterations Associated with Metabolic Syndrome in Mice.

María De La Fuente-Fernández,Nuria Fernández,Antonio Manuel Inarejos-García,Marin Prodanov,Sara Amor,Luis Santamaría,Antonio Tejera-Muñoz,Angel Luis García-Villalón,Paula Almodóvar,Laura Andrés-Delgado,Miriam Granado,Daniel González-Hedström,Luis Monge

doi:10.3390/antiox9040339

María De La Fuente-Fernández, Nuria Fernández + Show 11 more

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https://doi.org/10.3390/antiox9040339

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Abstract

The incidence of metabolic syndrome (MetS) is increasing worldwide which makes necessary the finding of new strategies to treat and/or prevent it. The aim of this study was to analyze the possible beneficial effects of a carob fruit extract (CSAT+®) on the cardiometabolic alterations associated with MetS in mice. 16-week-old C57BL/6J male mice were fed for 26 weeks either with a standard diet (chow) or with a diet rich in fats and sugars (HFHS), supplemented or not with 4.8% of CSAT+®. CSAT+® supplementation reduced blood glucose, Homeostatic Model Assessment of Insulin Resistance (HOMA-IR) and circulating levels of total cholesterol, low-density lipoprotein (LDL) cholesterol (LDL-c), insulin, and interleukin-6 (IL-6). In adipose tissue and skeletal muscle, CSAT+® prevented MetS-induced insulin resistance, reduced macrophage infiltration and the expression of pro-inflammatory markers, and up-regulated the mRNA levels of antioxidant markers. Supplementation with CSAT+® prevented MetS-induced hypertension and decreased the vascular response of aortic rings to angiotensin II (AngII). Moreover, treatment with CSAT+® attenuated endothelial dysfunction and increased vascular sensitivity to insulin. In the heart, CSAT+® supplementation reduced cardiomyocyte apoptosis and prevented ischemia-reperfusion-induced decrease in cardiac contractility. The beneficial effects at the cardiovascular level were associated with a lower expression of pro-inflammatory and pro-oxidant markers in aortic and cardiac tissues.

Highlights

Metabolic syndrome (MetS) is a pathologic condition characterized by abdominal obesity, insulin resistance, hypertension, and hyperlipidemia
We show the beneficial effects of CSAT+®, a proprietary blend of carob (Ceratonia silique L.) pods and seeds extract together with FOS, improving the metabolic and cardiovascular alterations associated to metabolic syndrome (MetS) in mice
Our results show that supplementation with CSAT+® does not affect body weight gain or adiposity in mice fed a high fat/high sucrose diet (HFHS) diet

Summary

Introduction

Metabolic syndrome (MetS) is a pathologic condition characterized by abdominal obesity, insulin resistance, hypertension, and hyperlipidemia. There is no consensus about the etiology of MetS, it is clear that the state of chronic low-grade inflammation plays a major role in both the initiation of the syndrome and in the development of its associated pathologies [5,6]. The inflammatory state may have its origin in visceral adipose tissue as a result of both structural and functional alterations of adipocytes which include decreased plasticity, hypertropia, hyperplasia, and inability to buffer the excess nutrient intake derived from the positive energetic balance, which results in a dyslipidemic state and in the development of insulin resistance [5]. The chronic exposure to inflammatory cytokines and fatty acids induces alterations in the activation of intracellular pathways in several organs and tissues. In insulin-dependent tissues such as skeletal muscle and adipose tissue, there is a reduction in the activation of the phosphoinositide 3-kinase (PI3K)/Akt pathway which derives in decreased translocation of glucose transporter 4 (GLUT-4) to the cell membrane and the consequent reduction in glucose uptake and hyperglycemia [6]

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