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.

Stabilized soy protein emulsion enriched with silicon and containing or not methylcellulose as novel technological alternatives to reduce animal fat digestion.

During the last decade, the consumption of animal saturated fat has been associated with an increased risk of chronic disease. Experience shows that changing the dietary habits of the population is a complicated and slow process, so technological strategies offer new possibilities for the development of functional foods. The present work is focused on studying the impact of using a food-grade non-ionic hydrocolloid (methylcellulose; MC) and/or the inclusion of silicon (Si) as a bioactive compound in pork lard emulsions stabilized with soy protein concentrate (SPC), on the structure, rheology, lipid digestibility and Si bioaccesibility during in vitro gastrointestinal digestion (GID). Four emulsions (SPC, SPC/Si, SPC/MC and SPC/MC/Si) were prepared with a final biopolymer (SPC and/or MC) concentration of 4% and 0.24% Si. The results showed a lower degree of lipid digestion in SPC/MC compared with SPC, specifically at the end of the intestinal phase. Moreover, Si partially reduced fat digestion only when incorporated into the SPC-stabilized emulsion, while this effect was lost in SPC/MC/Si. This was probably due to its retention inside the matrix emulsion, which resulted in lower bioaccesibility than in SPC/Si. Additionally, the correlation between the flow behavior index (n) and the lipid absorbable fraction was significant, suggesting that n can be a predictive marker of the extent of lipolysis. Concretely, our results revealed that SPC/Si and SPC/MC can be used as pork fat digestion reducers and thus, they can replace pork lard in the reformulation of animal products with potential health benefits.

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.

The Influence of Cellulose Ethers on the Physico-Chemical Properties, Structure and Lipid Digestibility of Animal Fat Emulsions Stabilized by Soy Protein.

This study explores the influence of carboxymethylcelullose (CMC) and methylcelullose (MC), added by simultaneous (sim) and sequential (seq) emulsification methods, on the structure, rheological parameters and in vitro lipid digestibility of pork lard O/W emulsions stabilized by soy protein concentrate (SPC). Five emulsions (SPC, SPC/CMC-sim, SPC/CMC-seq SPC/MC-sim, SPC/MC-seq) were prepared in vitro. The presence of CMC and MC, and the stage of incorporation affected the emulsion microstructure. In the SPC emulsion, lipid droplets were entrapped by a protein layer that was thicker when MC was added, providing greater resistance against environmental stresses during gastrointestinal digestion. At 37 °C, CMC incorporation produced a structural reinforcement of the SPC emulsion, whereas MC addition did not affect the network rigidity, although a delaying effect on the crossover temperature was observed, which was more evident in SPC/MC-seq. The presence and stage of CMC and MC incorporation affected the rate and extent of lipolysis, with SPC/MC-seq presenting an inferior concentration of free fatty acids. The lower extent of lipolysis observed in SPC/MC-seq may be positive in the manufacture of animal fat products in which reduced fatty acid absorption is intended.

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)

Carob fruit extract-enriched meat improves pancreatic beta-cell dysfunction, hepatic insulin signaling and lipogenesis in late-stage type 2 diabetes mellitus model.

The inclusion of functional bioactive compounds of dietary fiber in meat products has been demonstrated to exert a significant impact on human health. Carob fruit extract (CFE) is a dietary fiber rich in proanthocyanidins with known antioxidant, hypolipidemic and hypoglycemic effects. Consumption of CFE-enriched meat (CFE-RM) may provide interesting benefits in late-stage type 2 diabetes mellitus (T2DM). To explore the antidiabetic mechanisms of CFE-RM, we used a model of late-stage T2DM in Wistar rats fed a high-saturated-fat/high-cholesterol diet (Chol-diet) and injected streptozotocin plus nicotinamide (D group). The effects of CFE-RM were tested by incorporating it into the diet as preventive strategy (ED group) or curative treatment (DE group). CFE-RM had a positive effect on glycemia, enhancing hepatic insulin sensitivity and improving pancreatic ß-cell regeneration in both ED and DE groups. Western blotting and immunohistochemistry suggested that CFE-RM increased levels of insulin receptor ß and phosphatidylinositol-3-kinase, as well as the downstream target phospho-Akt (at Ser473). CFE-RM also up-regulated glucose transporter 2, which improves the insulin-mediated glucose uptake by the liver, and promoted phosphorylation of glycogen synthesis kinase-3ßprotein (at ser9), consequently increasing the hepatic glycogen content. In addition, CFE-RM decreased fatty liver by suppressing de novo lipogenesis activation due to down-regulation of liver X receptor-α/ß, sterol regulatory element binding protein-1c and carbohydrate-response element-binding protein transcription factors. Our findings suggest that the consumption of CFE-RM included in the diet as a functional food should be considered as a suitable nutritional strategy to prevent or manage late-stage T2DM.