Carob Extract Supplementation Together with Caloric Restriction and Aerobic Training Accelerates the Recovery of Cardiometabolic Health in Mice with Metabolic Syndrome

Carob, the fruit of Ceratonia siliqua L. exerts antidiabetic, anti-inflammatory, and antioxidant effects and could be a useful strategy for the treatment and/or prevention of metabolic syndrome (MetS). The aim of this study was to analyze whether supplementation with a carob fruit extract (CSAT+(R)), alone or in combination with aerobic training, accelerates the recovery of cardiometabolic health in mice with MetS subjected to a caloric restriction. For this purpose, mice were fed with a high fat (58% kcal from fat)/high sugar diet for 23 weeks to induce MetS. During the next two weeks, mice with MetS were switched to a diet with a lower caloric content (25% kcal from fat) supplemented or not with CSAT+(R) (4.8%) and/or subjected to aerobic training. Both caloric reduction and aerobic training improved the lipid profile and attenuated MetS-induced insulin resistance measured as HOMA-IR. However, only supplementation with CSAT+(R) enhanced body weight loss, increased the circulating levels of adiponectin, and lowered the plasma levels of IL-6. Moreover, CSAT+(R) supplementation was the only effective strategy to reduce the weight of epidydimal adipose tissue and to improve insulin sensitivity in the liver and in skeletal muscle. Although all interventions improved endothelial function in aorta segments, only supplementation with CSAT+(R) reduced obesity-induced hypertension, prevented endothelial dysfunction in mesenteric arteries, and decreased the vascular response of aorta segments to the vasoconstrictor AngIl. The beneficial cardiometabolic effects of CSAT+(R) supplementation, alone or in combination with aerobic training, were associated with decreased mRNA levels of pro-inflammatory markers such as MCP-1, TNF alpha, IL-1 beta, and IL-6 and with increased gene expression of antioxidant enzymes, such as GSR, GPX-3, and SOD-1 in the liver, gastrocnemius, retroperitoneal adipose tissue, and aorta. In conclusion, supplementation with CSAT+(R), alone or in combination with aerobic training, to mice with MetS subjected to caloric restriction for two weeks enhances body weight loss, improves the lipid profile and insulin sensitivity, and exerts antihypertensive effects through its anti-inflammatory and antioxidant properties.