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.

Whole Alga, Algal Extracts, and Compounds as Ingredients of Functional Foods: Composition and Action Mechanism Relationships in the Prevention and Treatment of Type-2 Diabetes Mellitus.

Type-2 diabetes mellitus (T2DM) is a major systemic disease which involves impaired pancreatic function and currently affects half a billion people worldwide. Diet is considered the cornerstone to reduce incidence and prevalence of this disease. Algae contains fiber, polyphenols, ω-3 PUFAs, and bioactive molecules with potential antidiabetic activity. This review delves into the applications of algae and their components in T2DM, as well as to ascertain the mechanism involved (e.g., glucose absorption, lipids metabolism, antioxidant properties, etc.). PubMed, and Google Scholar databases were used. Papers in which whole alga, algal extracts, or their isolated compounds were studied in in vitro conditions, T2DM experimental models, and humans were selected and discussed. This review also focuses on meat matrices or protein concentrate-based products in which different types of alga were included, aimed to modulate carbohydrate digestion and absorption, blood glucose, gastrointestinal neurohormones secretion, glycosylation products, and insulin resistance. As microbiota dysbiosis in T2DM and metabolic alterations in different organs are related, the review also delves on the effects of several bioactive algal compounds on the colon/microbiota-liver-pancreas-brain axis. As the responses to therapeutic diets vary dramatically among individuals due to genetic components, it seems a priority to identify major gene polymorphisms affecting potential positive effects of algal compounds on T2DM treatment.

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.

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 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.

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.

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.

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.

Effect of seaweed and cholesterol-enriched diets on postprandial lipoproteinaemia in rats.

High postprandial lipaemia increases cardiovascular risk. Algae consumption may affect postprandial lipoproteinaemia. The effects of dietary alga and cholesterol supplementation on postprandial lipaemia and lipoproteinaemia and arylesterase (AE) activity in growing male Wistar rats were tested in the present study. Six groups of ten rats were fed a casein-based diet for 3 weeks. Three of the diets contained 2.4 % cholesterol-raising agent (Chol), while the other three did not (NChol). Seven percentage of the control diets (NChol-C and Chol-C) consisted of a cellulose-wheat starch mix (35:65), while the Nori alga diets (NChol-N and Chol-N) and Konbu diets (NChol-K and Chol-K) contained 7 % of each respective freeze-dried alga. Postprandial plasma was obtained after a 3 h diet withdrawal. Supplementary cholesterol and alga type significantly affected (at least P < 0.05) the cholesterol, TAG, phospholipid and protein contents of the various lipoprotein fractions. AE enzyme activity increased (P < 0.05) in NChol rats given Nori and Konbu diets. NChol-K, but not NChol-N, rats displayed higher (P < 0.05) plasma cholesterol, TAG and phospholipid levels than NChol-C animals. NChol-K rats presented higher TAG, phospholipid, protein and lipoprotein mass values than their NChol-C counterparts. Inclusion of algae in Chol diets decreased (P < 0.001) the postprandial hypertriacylglycerolaemia. The Chol-N diet affected most lipoprotein fraction contents. Chol-N rats had lower postprandial cholesterolaemia and a better lipoprotein profile (fewer LDL and a tendency toward more HDL and fewer cholesterol-enriched VLDL) than Chol-K rats, suggesting that Nori is the alga of choice in dietary treatment of hypercholesterolaemia.

Effects of seaweed-restructured pork diets enriched or not with cholesterol on rat cholesterolaemia and liver damage.

Seaweed enriched-restructured pork (RP) is a potential functional food. However, indications of adverse effects associated with herbal medications, which include among others liver failure, toxic hepatitis, and death have been reported. Cholesterol feeding produces hepatomegalia and fat liver infiltration. The effect of seaweed-RP diet, cholesterol-enriched or not, on plasma cholesterol, liver damage markers, structure, and cytochrome CYP4A-1 were evaluated after 5 wk. Eight rat groups were fed a mix of 85% AIN-93M rodent-diet plus 15% RP. The Cholesterol-control (CC), Cholesterol-Wakame (CW), Cholesterol-Nori (CN) and Cholesterol-Sea Spaghetti (CS) groups respectively consumed similar diets to control (C), Wakame (W), Nori (N), and Sea Spaghetti (S) but as part of hypercholesterolaemic diets. CN and CS significantly blocked the hypercholesterolaemic effect observed in CC group. After 5-wk, N and S diets increased the CYP4A-1 expression. However, seaweed-RPs were unable to reduce the histological liver alterations observed in CC group. Larger and more abundant hepatocellular alterations were found in CS and CN rats suggesting that the hypocholesterolaemic effects of these seaweed-RPs seem to be a two-edged sword as they increased liver damage. Future studies are needed to understand the involved mechanisms.

Characteristics and nutritional and cardiovascular-health properties of seaweeds.

While marine algae have traditionally formed part of the Oriental diet, their major use in Western countries has been in the phytocolloid industry. Only a few coastal communities outside Asia have customarily used seaweeds as components of special dishes. Of late, however, seaweeds have gained importance as foodstuffs in Western countries and most recently as components of functional foods because of their high dietary fiber, mineral, vitamin, and phytochemical content, low energy levels, and high concentrations of certain polyunsaturated fatty acids. The present paper reviews the available data for some of the components of the major edible algae and studies several factors that can affect their physiochemical properties (e.g., hydration, water and oil-holding capacity, fermentability, binding capacity, etc.) and, in turn, their nutritional importance. The effects of marine alga consumption on growth and body weight, mineral availability, lipid metabolism, blood pressure, and antioxidant properties are reviewed, together with preliminary data on the effects of some functional foods containing seaweeds on lipid metabolism and gene expression of enzymes engaged in antioxidant protection. This review concludes with some remarks regarding the danger of the improper use of seaweeds in herbal medications. In addition, as the properties of algae are highly dependent on their individual composition, any generalization regarding these properties may be considered misleading and scientifically inappropriate.

Differential effects of konbu and nori seaweed dietary supplementation on liver glutathione status in normo- and hypercholesterolaemic growing rats.

The effects of six balanced diets for 3 weeks on dietary intake, growth, liver weight and fat, plasma cholesterol, total antioxidant capacity, liver glutathione status and antioxidant enzymes in growing male Wistar rats were studied. Ten rats per group were fed casein- and soyabean-based diets with or without 2.4 % cholesterol-raising agent. Seven percent of the diet consisted of a cellulose-wheat starch mix (35:65; control diets), freeze-dried nori (nori diets) or konbu (konbu diets). The 7 % dietary supplement of seaweeds was well accepted and induced normal growth rates in rats. Except for food intake, total and reduced glutathione and total antioxidant capacity, dietary cholesterol addition significantly affected (at least P<0.05) all parameters studied. Alga consumption affected total and reduced glutathione, glutathione reductase activity, plasma cholesterol, and total and cholesterol-adjusted total antioxidant capacity (at least P<0.05). A significant cholesterol-alga interaction was found for liver weight, total glutathione peroxidase (GSH-Px) and the Se-dependent GSH-Px:total GSH-Px ratio (at least P<0.05). GSH-Px activity increased in cholesterol-fed nori rats mainly as Se-dependent GSH-Px, while in konbu and control groups the GSH-Px activity was related to increases in both non-Se-dependent and Se-dependent GSH-Px activities. The decrease in the antioxidant status of konbu rats was related to the high As content of this alga, which led to a compensatory increase in glutathione reductase activity in these animals. In conclusion, although some antioxidant compounds are present in algae, other dietary compounds, such as As, induced poor antioxidant status in rats.