Silicon as a Functional Meat Ingredient Improves Jejunal and Hepatic Cholesterol Homeostasis in a Late-Stage Type 2 Diabetes Mellitus Rat Model.

Silicon included in a restructured meat (RM) matrix (Si-RM) as a functional ingredient has been demonstrated to be a potential bioactive antidiabetic compound. However, the jejunal and hepatic molecular mechanisms by which Si-RM exerts its cholesterol-lowering effects remain unclear. Male Wistar rats fed an RM included in a high-saturated-fat high-cholesterol diet (HSFHCD) combined with a low dose of streptozotocin plus nicotinamide injection were used as late-stage type 2 diabetes mellitus (T2DM) model. Si-RM was included into the HSFHCD as a functional food. An early-stage TD2M group fed a high-saturated-fat diet (HSFD) was taken as reference. Si-RM inhibited the hepatic and intestinal microsomal triglyceride transfer protein (MTP) reducing the apoB-containing lipoprotein assembly and cholesterol absorption. Upregulation of liver X receptor (LXRα/ß) by Si-RM turned in a higher low-density lipoprotein receptor (LDLr) and ATP-binding cassette transporters (ABCG5/8, ABCA1) promoting jejunal cholesterol efflux and transintestinal cholesterol excretion (TICE), and facilitating partially reverse cholesterol transport (RCT). Si-RM decreased the jejunal absorptive area and improved mucosal barrier integrity. Consequently, plasma triglycerides and cholesterol levels decreased, as well as the formation of atherogenic lipoprotein particles. Si-RM mitigated the dyslipidemia associated with late-stage T2DM by Improving cholesterol homeostasis. Silicon could be used as an effective nutritional approach in diabetic dyslipidemia management.

The preventive and therapeutic consumption of meat enriched with carob fruit extract, rich in phenolic compounds, improves colonic antioxidant status in late-stage T2DM rats.

Oxidative stress is prevalent in Type 2 Diabetes Mellitus (T2DM) and has been associated with high meat consumption. Carob Fruit Extract (CFE) contains phenolic compounds, making it a suitable functional ingredient. Current study aims to evaluate the effect of CFE-enriched meat (CFE-meat) consumption on the antioxidant status of proximal and distal colon, and its relationship with fecal phenolic compounds in late-stage T2DM rats. Three groups of eight rats were studied: 1) D, fed control-meat; 2) ED, fed CFE-meat since the beginning of the study; 3) DE, fed CFE-meat after confirming T2DM. CFE-meat consumption reduces colonic oxidative stress mainly in the proximal section and helps to ameliorate glutathione metabolism and antioxidant score. Difference between ED and DE groups were associated with colon homeostasis and T2DM progression suggesting greater fermentation but lower absorption in the DE group. CFE appears as a promising tool to improve the antioxidant status observed in late-stage T2DM.

Analysis of immunohistomorphological changes in the colonic mucosa in a high-saturated fat and high-cholesterol fed streptozotocin/nicotinamide diabetic rat model.

The mucosal surface of gastrointestinal tract is lined with epithelial cells that establish an effective barrier between the lumen and internal environment through intercellular junctions, preventing the passage of potentially harmful substances. The "intestinal barrier function" consist of a defensive system that prevent the passage of antigens, toxins, and microbial products, while maintains the correct development of the epithelial barrier, the immune system and the acquisition of tolerance toward dietary antigens and intestinal microbiota. Intestinal morphology changes subsequent to nutritional variations, stress, aging or diseases, which can also affect the composition of the microbiota, altering the homeostasis of the intestine. A growing body of evidence suggests that alterations in intestinal barrier function favor the development of exaggerated immune responses, leading to metabolic endotoxemia, which seems to be the origin of many chronic metabolic diseases such as type 2 diabetes mellitus (T2DM). Although the mechanisms are still unknown, the interaction between dietary patterns, gut microbiota, intestinal mucosa, and metabolic inflammation seems to be a key factor for the development of T2DM, among other diseases. This chapter details the different techniques that allow evaluating the morphological and molecular alterations that lead of the intestinal barrier dysfunction in a T2DM experimental model. To induce both diabetic metabolic disturbances and gut barrier disruption, Wistar rats were fed a high-saturated fat and high-cholesterol diet and received a single dose of streptozotocin/nicotinamide. This animal model may contribute to clarify the understanding of the role of intestinal barrier dysfunction on the late-stage T2DM etiology.

Silicon-enriched meat positively improves plasma lipidaemia and lipoproteinaemia, LDLr, and insulin capability and the signalling pathway induced by an atherogenic diet in late-stage type 2 diabetes mellitus rats.

The impact of silicon as a functional ingredient in restructured meat (RM) on lipoprotein composition, metabolism, and oxidation on type 2 diabetes mellitus (T2DM) markers has never been studied. This study aims to evaluate the effect of silicon-enriched-meat consumption on lipidaemia, lipoprotein profile and metabolism, plasma arylesterase, and TBARS and their relationships with glycaemia, insulinaemia, and insulin-signaling markers in late-stage-T2DM rats fed a high-saturated-fat-high-cholesterol (HSFHC) diet. Saturated-fat diets with or without added cholesterol were formulated by mixing a 70% purified diet with 30% freeze-dried RM with or without added silicon. Three groups of seven Wistar rats each were tested. The ED group received the control RM in the framework of a high-saturated-fat diet as early-stage T2DM control. The other two groups received streptozotocin-nicotinamide administration together with the HSFHC diet containing the control RM (LD) or silicon-enriched RM (LD-Si). Scores were created to define the diabetic trend and dyslipidaemia. The ED rats showed hyperglycaemia, hyperinsulinaemia, hypertriglyceridaemia, and triglyceride-rich-VLDLs, suggesting they were in early-stage T2DM. LD rats presented hyperglycaemia, hypoinsulinaemia, and reduced HOMA-beta and insulin signaling markers typical of late-stage T2DM along with hypercholesterolaemia and high amounts of beta-VLDL, IDL, and LDL particles and low arylesterase activity. All these markers were significantly (p < 0.05) improved in LD-Si rats. The diabetic trend and diabetes dyslipidaemia scores showed a high and significant correlation (r = 0.595, p < 0.01). Silicon-enriched-meat consumption counterbalances the negative effects of HSFHC diets, functioning as an active hypolipemic, antioxidant, and antidiabetic dietary ingredient in a T2DM rat model, delaying the onset of late-stage diabetes.

Impact of Silicon Addition on the Development of Gelled Pork Lard Emulsions with Controlled Lipid Digestibility for Application as Fat Replacers.

Pork lard gelled emulsions stabilized with two proteins [soy protein concentrate (SPC) or a pork rind protein extract (PRP)], both with and without added silicon (Si) from diatomaceous earth powder, were gelled by microbial transglutaminase and к-carrageenan. These gelled emulsions (GEs), intended as fat replacers, were evaluated in different aspects, including microstructure and technological properties during chilling storage. In addition, in vitro gastrointestinal digestion (GID) with an analysis of lipolysis and lipid digestibility was also evaluated. All GEs showed adequate technological properties after 28 days of chilling storage, although the SPC-stabilized GEs showed better gravitational and thermal stability (~4% and ~6%, respectively) during chilling storage than the PRP-stabilized ones (~8 and ~12%, respectively). PRP developed larger flocculates restricting pancreatic lipase-mediated lipolysis during intestinal digestion. The addition of Si to both GE structures protected them against disruption during in vitro digestion. Accordingly, Si appears to slow down fat digestion, as reflected by higher triacylglycerides content after GID (15 and 22% vs. 10 and 18% in GEs without Si) and could become a potential candidate for use in the development of healthier meat products.

The bitter taste receptor (TAS2R) agonist denatonium promotes a strong relaxation of rat corpus cavernosum.

Bitter taste receptors (TAS2R) are found in numerous extra-oral tissues, including smooth muscle (SM) cells in both vascular and visceral tissues. Upon activation, TAS2R stimulate the relaxation of the SM. Nitric oxide (NO)/cyclic guanosine monophosphate (cGMP) signaling pathway is involved in penile erection, and type 5 phosphodiesterase (PDE5) inhibitors, a cGMP-specific hydrolase are used as first-line treatments for erectile dysfunction (ED). Nevertheless, PDE5 inhibitors are ineffective in a considerable number of patients, prompting research into alternative pharmacological targets for ED. Since TAS2R agonists regulate SM contractility, this study investigates the role of TAS2Rs in rat corpus cavernosum (CC). We performed immunohistochemistry to detect TAS2R10, isometric force recordings for TAS2R agonists denatonium and chloroquine, the slow-release H2S donor GYY 4137, the NO donor SNAP, the ß-adrenoceptor agonist isoproterenol and electrical field stimulation (EFS), as well as measurement of endogenous hydrogen sulfide (H2S) production. The immunofluorescence staining indicated that TAS2R10 was broadly expressed in the CC SM and to some extent in the nerve fibers. Denatonium, chloroquine, SNAP, and isoproterenol cause potent dose-dependent SM relaxations. H2S production was decreased by NO and H2S synthase inhibitors, while it was enhanced by denatonium. In addition, denatonium increased the relaxations induced by GYY 4137 and SNAP but failed to modify EFS- and isoproterenol-induced responses. These results suggest neuronal and SM TAS2R10 expression in the rat CC, where denatonium induces a strong SM relaxation per se and promotes the H2S- and NO-mediated inhibitory gaseous neurotransmission. Thus, TAS2R10 might represent a valuable therapeutic target in ED.

Proanthocyanidins: Impact on Gut Microbiota and Intestinal Action Mechanisms in the Prevention and Treatment of Metabolic Syndrome.

The metabolic syndrome (MS) is a cluster of risk factors, such as central obesity, hyperglycemia, dyslipidemia, and arterial hypertension, which increase the probability of causing premature mortality. The consumption of high-fat diets (HFD), normally referred to high-saturated fat diets, is a major driver of the rising incidence of MS. In fact, the altered interplay between HFD, microbiome, and the intestinal barrier is being considered as a possible origin of MS. Consumption of proanthocyanidins (PAs) has a beneficial effect against the metabolic disturbances in MS. However, there are no conclusive results in the literature about the efficacy of PAs in improving MS. This review allows a comprehensive validation of the diverse effects of the PAs on the intestinal dysfunction in HFD-induced MS, differentiating between preventive and therapeutic actions. Special emphasis is placed on the impact of PAs on the gut microbiota, providing a system to facilitate comparison between the studies. PAs can modulate the microbiome toward a healthy profile and strength barrier integrity. Nevertheless, to date, published clinical trials to verify preclinical findings are scarce. Finally, the preventive consumption of PAs in MS-associated dysbiosis and intestinal dysfunction induced by HFD seems more successful than the treatment strategy.

Could Duodenal Molecular Mechanisms be Involved in the Hypocholesterolemic Effect of Silicon Used as Functional Ingredient in Late-Stage Type 2 Diabetes Mellitus?

SCOPE: Hypercholesterolemia increases the risk of mortality in type 2 diabetes mellitus (T2DM), especially in the late-stage. Consumption of bioactive compounds as functional ingredients would help achieve therapeutic goals for cholesterolemia. Silicon has demonstrated a hypocholesterolemic effect and the ability to reduce fat digestion. However, it is unclear whether silicon exerts such effect in late-stage T2DM (LD) and the intestinal mechanisms involved. METHODS AND RESULTS: Three groups of eight rats were included: early-stage T2DM control (ED), LD, and the LD group treated with silicon (LD-Si) once the rats were diabetic. Morphological alterations of the duodenal mucosa, and levels of markers involve in cholesterol absorption and excretion, beside cholesterolemia, and fecal excretion were assayed. Silicon included as a functional ingredient significantly reduces cholesterolemia in part due to: 1) reducing cholesterol intestinal absorption by decreasing the absorptive area and Acetyl-Coenzyme A acetyltransferase-2 (ACAT2) levels; and 2) increasing cholesterol excretion to the lumen by induction of the liver X receptor (LXR) and consequent increase of adenosine triphosphate-binding cassette transporter (ABCG5/8). CONCLUSIONS: These results provide insight into the intestinal molecular mechanisms by which silicon reduces cholesterolemia and highlights the efficacy of the consumption of silicon-enriched functional foods in late-stage T2DM.

Efectos protectores de las proantocianidinas a nivel intestinal frente a estrés termooxidativo por ingestión de aceite de girasol utilizado en fritura / Protective effects of proanthocyanidins at the intestinal levelagainst thermooxidative stress due to ingestion of sunflower oil used in frying

La fritura repetida de alimentos produce termooxidación y polimerización, potencialmente negativas para la salud. Se desconoce cómo reacciona el sistema gastrointestinal frente a estos compuestos. Las proantocianidinas poseen propiedades antioxidantes e hipolipemiantes. Hipotetizamos que un extracto de algarrobo rico en proantocianidinas (CFE) mejora la defensa del intestino frente a la agresión termooxidativa. Se estudió, en el aceite de girasol, la termooxidación producida por la fritura repetida de pescado y, en ratas Wistar, el efecto de administrar conjuntamente aceite de fritura y CFE sobre: la digestión de los compuestos termooxidados, la lipemia postprandial, las proteínas implicadas en la absorción de lípidos, y la actividad y expresión antioxidante y de hemo-oxigenasa-1 en intestino delgado. Doce ratas Wistar, macho, de 200-250 g fueron canuladas durante una semana con la mezcla del aceite termooxidado-CFE o con aceite termooxidado. Se cuantificó la alteración termooxidativa en el aceite de fritura y en la grasa post-prandial del lumen gastrointestinal, la lipemia postprandial, las proteínas NPC1L1, ACAT-2 y MTP, y el estado antioxidante en duodeno, yeyuno e íleon. Se encontraron niveles elevados de compuestos de polimerización y triglicéridos oxidados en el aceite de girasol y en la grasa del lumen gastrointestinal. La administración de aceite de girasol termooxidado-CFE disminuye la digestibilidad del aceite y de los compuestos poliméricos/termooxidados, aminora la lipemia postprandial, eleva NPC1L1, ACAT-2 y MTP, y mejora el estado antioxidante intestinal y la excreción de polímeros fecales. El empleo de CFE reduce la lipemia postprandial y garantiza un estado antioxidante intestinal adecuado frente a lípidos termooxidados.(AU)

The repeated frying of food in sunflower oil produces thermo-oxidation and polymerization, potentially negative for health. The reaction of the gastrointestinal system to these compounds is unknown. Proanthocyanidins have antioxidant and lipid-lowering properties. We hypothesize that a carob-fruit extract rich in proanthocyanidins (CFE) improves the defense of the intestine against thermo-oxidative aggression. In sunflower oil, the thermo-oxidation produced by repeated frying of fish was studied while, in Wistar rats, the effect of jointly administering altered sunflower oil and CFE on: the digestion of thermo-oxidized compounds, postprandial lipaemia, proteins involved in lipid absorption, antioxidant and hemoxygenase-1 activity and expression in the small intestine. Twelve male Wistar rats, 200-250 g were cannulated for one week with the mixture of the thermo-oxidized oil-CFE or the thermo-oxidized oil. Thermo-oxidation was determined in sunflower oil and in the postprandial-fat of the gastrointestinal lumen, postprandial lipaemia, the proteins NPC1L1, ACAT-2 and MTP, and the antioxidant status in the duodenum, jejunum and ileum. High thermo-oxidation and polymerization levels were found on sunflower oil and fat in the gastrointestinal lumen. The administration of thermo-oxidized sunflower oil-CFE decreases the digestibility of the oil and the polymeric/thermo-oxidized compounds, reduces postprandial lipaemia, increases NPC1L1, ACAT-2, and MTP, and improves the intestinal antioxidant status and excretion of fecal polymers. The use of CFE reduces postprandial lipaemia and guarantees an adequate intestinal antioxidant status against thermo-oxidized lipids.(AU)