Angel Luis García-Villalón

Metabolic syndrome (MetS) is a multifactorial disorder characterized by central obesity, insulin resistance, dyslipidemia, and hypertension, all of which increase the risk of type 2 diabetes and cardiovascular diseases. This study investigates the potential complementary effects of the standardized green and black ADM ComplexTea Extract (CTE) and the heat-treated postbiotic (BPL1^® HT) on the cardiometabolic alterations associated with MetS in a murine model. C57BL/6J mice were fed a high-fat/high-sucrose (HFHS) diet and treated with CTE, BPL1^® HT, or their combination for 20 weeks. Metabolic, inflammatory, oxidative, vascular parameters, and fecal microbiota composition were assessed. Both CTE and BPL1^® HT individually attenuated weight gain, organ hypertrophy, insulin resistance, and inflammation. However, their combined administration exerted synergistic effects, fully normalizing body weight, adipocyte size, lipid profiles, HOMA-IR index, and insulin sensitivity to levels comparable to lean controls. Co-treatment also restored PI3K/Akt signaling in liver and muscle, reduced hepatic steatosis, and normalized the expression of inflammatory and oxidative stress markers across multiple tissues. Furthermore, vascular function was significantly improved, with enhanced endothelium-dependent relaxation and reduced vasoconstrictor responses, particularly to angiotensin II. CTE, BPL1^®HT, and the blend prevented bacterial richness reduction caused by HFHS; the blend achieved higher bacterial richness than mice in Chow diet. Additionally, the blend prevented the increase in Flintibacter butyricus, which is associated with MetS clinical parameters, and showed a tendency to increase the abundance of Bifidobacterium. These findings suggest that the combination of CTE and BPL1^® HT offers a potential nutritional strategy to counteract the metabolic and cardiovascular complications of MetS through complementary mechanisms involving improved insulin signaling, reduced inflammation and oxidative stress, enhanced vascular function, and modulation of gut microbiota.

Hypertension is associated with alterations in the composition and diversity of the intestinal microbiota. Indeed, supplementation with probiotics and prebiotics has shown promising results in modulating the gut microbiota and improving cardiovascular health. However, there are no studies regarding the possible beneficial effects of postbiotics on cardiovascular function and particularly on hypertension-induced cardiovascular alterations. Thus, the aim of this study was to analyze the effect of supplementation with the heat-treated Bifidobacterium animalis subsp. lactis CECT 8145 strain (BPL1™ HT), a postbiotic developed by the company ADM-Biopolis, on cardiovascular alterations induced by angiotensin II (AngII) infusion in mice. For this purpose, three groups of C57BL/6J male mice were used: (i) mice infused with saline (control); (ii) mice infused with AngII for 4 weeks (AngII); and (iii) mice supplemented with BPL1™ HT in the drinking water (1010 cells/animal/day) for 8 weeks and infused with AngII for the last 4 weeks (AngII + BPL1™ HT). AngII infusion was associated with heart hypertrophy, hypertension, endothelial dysfunction, and overexpression of proinflammatory cytokines in aortic tissue. BPL1™ HT supplementation reduced systolic blood pressure and attenuated AngII-induced endothelial dysfunction in aortic segments. Moreover, mice supplemented with BPL1™ HT showed a decreased gene expression of the proinflammatory cytokine interleukin 6 (Il-6) and the prooxidant enzymes NADPH oxidases 1 (Nox-1) and 4 (Nox-4), as well as an overexpression of AngII receptor 2 (At2r) and interleukin 10 (Il-10) in arterial tissue. In the heart, BPL1™ HT supplementation increased myocardial contractility and prevented ischemia–reperfusion-induced cardiomyocyte apoptosis. In conclusion, supplementation with the postbiotic BPL1™ HT prevents endothelial dysfunction, lowers blood pressure, and has cardioprotective effects in an experimental model of hypertension induced by AngII infusion in mice.

Arterial hypertension has a high prevalence in the population and is considered both a cardiovascular disease and an important risk factor for the development of other cardiovascular diseases. Tea consumption shows antihypertensive effects due to its composition in terms of bioactive substances such as flavan-3-ols and xanthines. The aim of this study was to assess the possible beneficial effects of two tea extracts, one of white tea (ADM^® White Tea; WTE) and another one composed of a mixture of black tea and green tea (ADM^® Tea Complex; CTE), on the cardiovascular alterations induced by angiotensin II (AngII) infusion in mice. For this purpose, four groups of C57BL/6J male mice were used: (1) mice fed on a standard diet for 8 weeks and infused with saline for the last 4 weeks (controls); (2) mice fed on a standard diet for 8 weeks and infused with AngII for the last 4 weeks (AngII); (3) mice fed on a standard diet supplemented with 1.6% WTE and infused with AngII for the last 4 weeks (AngII + WTE); (4) mice fed on a standard diet supplemented with 1.6% TC and infused with AngII for the last 4 weeks (AngII + CTE). Both tea extracts exerted anti-inflammatory and antioxidant effects in arterial tissue and reduced AngII-induced endothelial dysfunction in aorta segments. Moreover, supplementation with WTE or CTE reduced the Ang-II-induced overexpression of AT1R and increased AngII-induced downregulation of AT2R in arterial tissue. However, only supplementation with CTE significantly increased the circulating levels of angiotensin 1-7 and reduced systolic blood pressure. In the heart, supplementation with both tea extracts attenuated AngII-induced cardiac hypertrophy and reduced ischemia-reperfusion-induced oxidative stress and apoptosis in myocardial tissue. In conclusion, supplementation with WTE or CTE attenuates AngII-induced cardiovascular damage through their anti-inflammatory, antioxidant, and antiapoptotic effects. In addition, supplementation with CTE also exerts antihypertensive effects, and so it may constitute an avenue through which to support cardiovascular health.

Early overnutrition is associated with cardiometabolic alterations in adulthood, likely attributed to reduced insulin sensitivity due to its crucial role in the cardiovascular system. This study aimed to assess the long-term effects of early overnutrition on the development of cardiovascular insulin resistance. An experimental childhood obesity model was established using male Sprague Dawley rats. Rats were organized into litters of 12 pups/mother (L12-Controls) or 3 pups/mother (L3-Overfed) at birth. After weaning, animals from L12 and L3 were housed three per cage and provided ad libitum access to food for 6 months. L3 rats exhibited elevated body weight, along with increased visceral, subcutaneous, and perivascular fat accumulation. However, heart weight at sacrifice was reduced in L3 rats. Furthermore, L3 rats displayed elevated serum levels of glucose, leptin, adiponectin, total lipids, and triglycerides compared to control rats. In the myocardium, overfed rats showed decreased IL-10 mRNA levels and alterations in contractility and heart rate in response to insulin. Similarly, aortic tissue exhibited modified gene expression of TNFα, iNOS, and IL-6. Additionally, L3 aortas exhibited endothelial dysfunction in response to acetylcholine, although insulin-induced relaxation remained unchanged compared to controls. At the molecular level, L3 rats displayed reduced Akt phosphorylation in response to insulin, both in myocardial and aortic tissues, whereas MAPK phosphorylation was elevated solely in the myocardium. Overfeeding during lactation in rats induces endothelial dysfunction and cardiac insulin resistance in adulthood, potentially contributing to the cardiovascular alterations observed in this experimental model.

Melatonin is a hormone that regulates sleep–wake cycles and is mainly synthesized in the pineal gland from tryptophan after its conversion into serotonin. Under normal conditions, less than 5% of tryptophan is reserved for the synthesis of serotonin and melatonin. The remaining 95% is metabolized in the liver through the kynurenine pathway. Increased levels of proinflammatory cytokines and cortisol increase the metabolism of tryptophan through the kynurenine pathway and reduce its availability for the synthesis of melatonin and serotonin, which may cause alterations in mood and sleep. The standardized saffron extract (affron^®) has shown beneficial effects on mood and sleep disorders in humans, but the underlying mechanisms are not well understood. Thus, the aim of this work was to study the effects of affron^® supplementation on the kynurenine pathway and the synthesis of melatonin in rats. For this purpose, adult male Wistar rats were supplemented for 7 days with 150 mg/kg of affron^® or vehicle (2 mL/kg water) administered by gavage one hour before sleep. Affron^® supplementation reduced body weight gain and increased the circulating levels of melatonin, testosterone, and c-HDL. Moreover, animals supplemented with affron^® showed decreased serum levels of kynurenine, ET-1, and c-LDL. In the pineal gland, affron^® reduced Il-6 expression and increased the expression of Aanat, the key enzyme for melatonin synthesis. In the liver, affron^® administration decreased the mRNA levels of the enzymes of the kynurenine pathway Ido-2, Tod-2, and Aadat, as well as the gene expression of Il-1β and Tnf-α. Finally, rats treated with affron^® showed increased mRNA levels of the antioxidant enzymes Ho-1, Sod-1, Gsr, and Gpx-3, both in the liver and in the pineal gland. In conclusion, affron^® supplementation reduces kynurenine levels and promotes melatonin synthesis in rats, possibly through its antioxidant and anti-inflammatory effects, making this extract a possible alternative for the treatment and/or prevention of mood and sleep disorders.

Insulin resistance is one of the main characteristics of metabolic syndrome (MetS) and the main cause of the development of type II diabetes. The high prevalence of this syndrome in recent decades has made it necessary to search for preventive and therapeutic agents, ideally of natural origin, with fewer side effects than conventional pharmacological treatments. Tea is widely known for its medicinal properties, including beneficial effects on weight management and insulin resistance. The aim of this study was to analyze whether a standardized extract of green and black tea (ADM^® Complex Tea Extract (CTE)) prevents the development of insulin resistance in mice with MetS. For this purpose, C57BL6/J mice were fed for 20 weeks with a standard diet (Chow), a diet with 56% kcal from fat and sugar (HFHS) or an HFHS diet supplemented with 1.6% CTE. CTE supplementation reduced body weight gain, adiposity and circulating leptin levels. Likewise, CTE also exerted lipolytic and antiadipogenic effects in 3T3-L1 adipocyte cultures and in the C. elegans model. Regarding insulin resistance, CTE supplementation significantly increased plasma adiponectin concentrations and reduced the circulating levels of insulin and the HOMA-IR. Incubation of liver, gastrocnemius muscle and retroperitoneal adipose tissue explants with insulin increased the pAkt/Akt ratio in mice fed with Chow and HFHS + CTE but not in those fed only with HFHS. The greater activation of the PI3K/Akt pathway in response to insulin in mice supplemented with CTE was associated with a decrease in the expression of the proinflammatory markers Mcp-1, IL-6, IL-1β or Tnf-α and with an overexpression of the antioxidant enzymes Sod-1, Gpx-3, Ho-1 and Gsr in these tissues. Moreover, in skeletal muscle, mice treated with CTE showed increased mRNA levels of the aryl hydrocarbon receptor (Ahr), Arnt and Nrf2, suggesting that the CTE’s insulin-sensitizing effects could be the result of the activation of this pathway. In conclusion, supplementation with the standardized extract of green and black tea CTE reduces body weight gain, exerts lipolytic and antiadipogenic effects and reduces insulin resistance in mice with MetS through its anti-inflammatory and antioxidant effects.

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+^®), 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+^® (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+^® enhanced body weight loss, increased the circulating levels of adiponectin, and lowered the plasma levels of IL-6. Moreover, CSAT+^® 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+^® reduced obesity-induced hypertension, prevented endothelial dysfunction in mesenteric arteries, and decreased the vascular response of aorta segments to the vasoconstrictor AngII. The beneficial cardiometabolic effects of CSAT+^® supplementation, alone or in combination with aerobic training, were associated with decreased mRNA levels of pro-inflammatory markers such as MCP-1, TNFα, IL-1β, 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+^®, 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.

Hypertension is considered to be both a cardiovascular disease and a risk factor for other cardiovascular diseases, such as coronary ischemia or stroke. In many cases, hypertension occurs in the context of metabolic syndrome (MetS), a condition in which other circumstances such as abdominal obesity, dyslipidemia, and insulin resistance are also present. The high incidence of MetS makes necessary the search for new strategies, ideally of natural origin and with fewer side effects than conventional pharmacological treatments. Among them, the tea plant is a good candidate, as it contains several bioactive compounds such as caffeine, volatile terpenes, organic acids, and polyphenols with positive biological effects. The aim of this study was to assess whether two new standardized tea extracts, one of white tea (WTE) and the other of black and green tea (CTE), exert beneficial effects on the cardiovascular alterations associated with MetS. For this purpose, male C57/BL6J mice were fed a standard diet (Controls), a diet high in fats and sugars (HFHS), HFHS supplemented with 1.6% WTE, or HFHS supplemented with 1.6% CTE for 20 weeks. The chromatography results showed that CTE is more concentrated on gallic acid, xanthines and flavan-3-ols than WTE. In vivo, supplementation with WTE and CTE prevented the development of MetS-associated hypertension through improved endothelial function. This improvement was associated with a lower expression of proinflammatory and prooxidant markers, and—in the case of CTE supplementation—also with a higher expression of antioxidant enzymes in arterial tissue. In conclusion, supplementation with WTE and CTE prevents the development of hypertension in obese mice; as such, they could be an interesting strategy to prevent the cardiovascular disorders associated with MetS.

Olive-derived products, such as virgin olive oil (EVOO) and/or olive leaf extracts (OLE), exert anti-inflammatory, insulin-sensitizing and antihypertensive properties and may be useful for stabilizing omega 3 fatty acids (n-3 PUFA) due to their high content in antioxidant compounds. In this study, the addition of OLE 4:0.15 (w/w) to a mixture of algae oil (AO) rich in n-3 PUFA and EVOO (25:75, w/w) prevents peroxides formation after 12 months of storage at 30 °C. Furthermore, the treatment with the oil mixture (2.5 mL/Kg) and OLE (100 mg/Kg) to 24 month old Wistar rats for 21 days improved the lipid profile, increased the HOMA-IR and decreased the serum levels of miRNAs 21 and 146a. Treatment with this new nutraceutical also prevented age-induced insulin resistance in the liver, gastrocnemius and visceral adipose tissue by decreasing the mRNA levels of inflammatory and oxidative stress markers. Oil mixture + OLE also attenuated the age-induced alterations in vascular function and prevented muscle loss by decreasing the expression of sarcopenia-related markers. In conclusion, treatment with a new nutraceutical based on a mixture of EVOO, AO and OLE is a useful strategy for improving the stability of n-3 PUFA in the final product and to attenuate the cardiometabolic and muscular disorders associated with aging.