Nutritional Description of Processed Foods with Fibre-Related Nutrition Claims in Spain: The BADALI Project.

Fibre is one of the most beneficial nutrients for health and is very frequently used in nutrition claims (NCs) to promote foods. These claims may lead consumers to believe that products bearing them are healthy and/or healthier than those without them. The main objective of this work is to address this belief. This is the first exhaustive analysis of seven processed food types with fibre-related NCs (six cereal-based and one plant-based meat analogues) comparing them with those without these claims. The Spanish Food Database, BADALI, was used for this study. Results show that as many as 88.7% of processed foods with fibre-related NCs are classified as 'less healthy' according to the Nutrient Profile Model developed by the Pan American Health Organization (PAHO-NPM). When compared to foods without these NCs, similar results were obtained in the whole sample. Most of the observed divergences when analysing individual critical nutrients by food type indicate a deterioration of the nutritional quality. Foods with fibre-related NCs contained more fibre. The more frequent use of whole grain cereals or other fibre-specific ingredients may contribute to this. Some other nutritionally relevant differences were observed and half of them reflected a deterioration of the nutritional quality. In addition, these foods presented a lower prevalence of the organic version, as well as similar rates of mineral and vitamin fortification. Therefore, processed foods with fibre-related NCs are not healthy, nor present a better nutritional profile than those without.

Nutritional Description of Organic and Conventional Food Products in Spain: The BADALI Project.

Organic food and drink is undoubtedly a growing market. Consumers perceive organic food as healthy, and nutrition claims (NCs) and fortification may add to this perception. Whether this is true is still a matter of controversy, particularly for organic food products. We present here the first comprehensive study of large samples of six specific organic food types, analysing the nutritional quality (nutrient composition and "healthiness") as well as the use of NCs and fortification. In parallel, a comparison with conventional food is also carried out. For this purpose, the Food Database of products in the Spanish market, BADALI, was used. Four cereal-based and two dairy-substitute food types were analysed. Our results show that as many as 81% of organic foods are considered "less healthy" by the Pan American Health Organization Nutrient Profile Model (PAHO-NPM). Organic foods present a slightly improved nutrient profile compared to conventional foods. However, many of the differences, though statistically significant, are nutritionally irrelevant. Organic foods use NCs very frequently, more than conventional foods, with very little micronutrient fortification. The main conclusion of this work is that consumers' perception that organic food products are healthy is unfounded from a nutritional point of view.

Nutritional Description of Foods with Low- and No-Calorie Sweeteners in Spain: The BADALI Project.

The use of low- and no-calorie sweeteners (LNCS) in foods has increased in recent years in response to the negative effects of free sugar on health. However, the health impact of LNCS is still unclear. Studies of the prevalence of LNCS in foods have been published previously, including in Spain. However, the use of health (HCs) and nutrition claims (NCs) to promote these foods and a full nutritional characterization are largely lacking. For this purpose, we used the BADALI database with 4218 foods present in the Spanish market. Our results show that 9.3% of foods have LNCS (including both intense and polyols). Sucralose and acesulfame K were the intense sweeteners most frequently used (52.4% and 48.2%, respectively), whereas maltitol was the preferred polyol (20.3%). Of all foods with LNCS, 30% also had added sugar. Many more foods with LNCS presented HCs and NCs than those without. Sugar was the nutrient most frequently claimed in NCs for LNCS-containing foods, whereas vitamins were for those without these sweeteners. NCs compliance with regulation was similar in both conditions (60.1% for foods without and 63.9% for foods with LNCS). As expected, foods with LNCS had less total sugar content and energy. Surprisingly, the nutrient profile of yogurts with LNCS changed completely: less total and saturated fat, whereas more proteins and sodium. Biscuits with LNCS contained more fibre. The results of our study reveal that the prevalence of LNCS is becoming high in some food types in Spain and that foods containing LNCS are more frequently promoted with HCs/NCs. In addition, it confirms the general reduction in energy and sugar content expected in foods with LNCS. Furthermore, it suggests a reformulation of products beyond sugar content.

Sodium Content of Foods Sold in the Spanish Market. Results from the BADALI Project.

High sodium/salt intake is a risk factor for Non-Communicable Diseases (NCDs). Excess sodium intake has been associated with high coronary heart disease, stroke and high blood pressure. The sodium daily intake is above the recommendations in the world as well as in Spain. Reducing salt content in processed foods and ready meals is one of the main strategies for reducing sodium intake. The aim of the present work is to characterise the presence of sodium in foods sold in the Spanish market. We also study a possible shift in sodium content in products over the last few years. For this purpose, 3897 products included in the BADALI food database were analysed, classified into 16 groups (G). We found that 93.3% of all foods displayed the sodium/salt content in the nutrition declaration. Meat-processed and derivatives (G8) had the highest mean and median values for sodium content, followed by snacks (G15) and sauces (G14). Only 12.7% of foods were sodium-free (≤5 mg/100 g or 100 mL), 32.4% had very low sodium (≤40 mg/100 g or 100 mL) and 48.2% were low in sodium (≤120 mg/100 g or 100 mL). On the contrary, 47.2% were high in sodium according to the Pan American Health Organisation Nutrient Profile Model (PAHO-NPM), while there were 31.9% according to the Chile-NPM. The agreement between the two NPMs was considered 'substantial' (κ = 0.67). When sodium content was compared over the years, no decrease was observed. This analysis was performed in the entire food population, by food group and in matched products. Therefore, more effort should be made by all parties involved in order to decrease the sodium/salt intake in the population.

CDK11 Promotes Cytokine-Induced Apoptosis in Pancreatic Beta Cells Independently of Glucose Concentration and Is Regulated by Inflammation in the NOD Mouse Model.

Background: Pancreatic islets are exposed to strong pro-apoptotic stimuli: inflammation and hyperglycemia, during the progression of the autoimmune diabetes (T1D). We found that the Cdk11(Cyclin Dependent Kinase 11) is downregulated by inflammation in the T1D prone NOD (non-obese diabetic) mouse model. The aim of this study is to determine the role of CDK11 in the pathogenesis of T1D and to assess the hierarchical relationship between CDK11 and Cyclin D3 in beta cell viability, since Cyclin D3, a natural ligand for CDK11, promotes beta cell viability and fitness in front of glucose. Methods: We studied T1D pathogenesis in NOD mice hemideficient for CDK11 (N-HTZ), and, in N-HTZ deficient for Cyclin D3 (K11HTZ-D3KO), in comparison to their respective controls (N-WT and K11WT-D3KO). Moreover, we exposed pancreatic islets to either pro-inflammatory cytokines in the presence of increasing glucose concentrations, or Thapsigargin, an Endoplasmic Reticulum (ER)-stress inducing agent, and assessed apoptotic events. The expression of key ER-stress markers (Chop, Atf4 and Bip) was also determined. Results: N-HTZ mice were significantly protected against T1D, and NS-HTZ pancreatic islets exhibited an impaired sensitivity to cytokine-induced apoptosis, regardless of glucose concentration. However, thapsigargin-induced apoptosis was not altered. Furthermore, CDK11 hemideficiency did not attenuate the exacerbation of T1D caused by Cyclin D3 deficiency. Conclusions: This study is the first to report that CDK11 is repressed in T1D as a protection mechanism against inflammation-induced apoptosis and suggests that CDK11 lies upstream Cyclin D3 signaling. We unveil the CDK11/Cyclin D3 tandem as a new potential intervention target in T1D.

Nutrition Claims Frequency and Compliance in a Food Sample of the Spanish Market: The BADALI Study.

Nutrition claims (NCs) have been shown to affect customers' perceptions and behaviour. In Europe, they are regulated by Regulation (EC) No 1924/2006. The aim of this work was to analyse the prevalence and compliance of NCs according to this regulation in Spain. For this purpose, we used the BADALI database, which included 3197 foods present in the Spanish market. Our results show that 36.1% of all foods carried NCs, at a rate of 3.3 NCs/food. The prevalence was very heterogeneous among food groups. Nuts and seeds, legumes and non-alcoholic beverages were the groups with the highest prevalence. Micronutrients, fat, fibre and sugars were the nutrients most referred to in NCs. Overall, the compliance was low, with 49.2% NCs correct. Fibre and proteins were the nutrients with most correct NCs. Vegetables and non-alcoholic beverages were the food groups with the highest proportion of correct NCs. The main reason for incorrect NCs was because the amount of the nutrient was not stated in the label. The results of our study reveal that the aim of the European Commission to ensure a high level of protection for consumers regarding NCs has not been fulfilled. Therefore, we consider it crucial that European institutions invest in guaranteeing regulation compliance.

Nutrient Composition of Foods Marketed to Children or Adolescents Sold in the Spanish Market: Are They Any Better?

Healthy eating is essential for the growth and development of children and adolescents. Eating habits established in childhood continue into adulthood. In Spain, the frequent promotion of foods with low nutritional value is already considered a threat to the health of the population, particularly to children and adolescents. In this work, we analyse 3209 foods from the Food Database, BADALI. Foods were classified as marketed to children or adolescents according to the advertising on the packaging, television or internet. We found that 17.5% of foods in the database were marketed to this population and 97% of those were considered unhealthy following the Pan American Health Organization Nutrient Profile Model (PAHO-NPM). In the total of foods for children or adolescents, 61.5% were high in fat, 58.5% in free-sugar, 45.4% in saturated fat and 45% in sodium. Foods marketed to them presented higher amounts of carbohydrates and sugar, while lower protein and fibre content than the rest. There was also considerable variability in levels of the other nutrients found in these products, which depended largely on the food group. According to our findings, there is a tendency for products marketed to children or adolescents to be unhealthy and of a poorer nutritional quality than those not targeted at them.

The role of oestrogens in the adaptation of islets to insulin resistance.

Pregnancy is characterized by peripheral insulin resistance, which is developed in parallel with a plasma increase of maternal hormones; these include prolactin, placental lactogens, progesterone and oestradiol among others. Maternal insulin resistance is counteracted by the adaptation of the islets of Langerhans to the higher insulin demand. If this adjustment is not produced, gestational diabetes may be developed. The adaptation process of islets is characterized by an increase of insulin biosynthesis, an enhanced glucose-stimulated insulin secretion (GSIS) and an increase of beta-cell mass. It is not completely understood why, in some individuals, beta-cell mass and function fail to adapt to the metabolic demands of pregnancy, yet a disruption of the beta-cell response to maternal hormones may play a key part. The role of the maternal hormone 17beta-oestradiol (E2) in this adaptation process has been largely unknown. However, in recent years, it has been demonstrated that E2 acts directly on beta-cells to increase insulin biosynthesis and to enhance GSIS through different molecular mechanisms. E2 does not increase beta-cell proliferation but it is involved in beta-cell survival. Classical oestrogen receptors ERalpha and ERbeta, as well as the G protein-coupled oestrogen receptor (GPER) seem to be involved in these adaptation changes. In addition, as the main production of E2 in post-menopausal women comes from the adipose tissue, E2 may act as a messenger between adipocytes and islets in obesity.

The role of estrogen receptors in the control of energy and glucose homeostasis.

Estrogens have been related to energy balance and glucose metabolism for a long time; however, the mechanisms involved in their actions are now being unveiled. The development of ERalpha and ERbeta knockout mice has demonstrated the participation of these receptors in the regulation of many processes related to the control of energy homeostasis. These include food intake and energy expenditure, insulin sensitivity in the liver and muscle, adipocyte growth and its body distribution as well as the pancreatic beta-cell function. In addition, other membrane receptors unrelated to ERalpha and ERbeta function in key tissues involved in energy balance and glucose homeostasis, i.e. the islet of Langerhans and the hypothalamus. Along with naturally occurring estrogens, there are endocrine disrupters that act as environmental estrogens and can impair the physiological action of ERalpha, ERbeta and other membrane ERs. New research is revealing a link between environmental estrogenic pollutants and the metabolic syndrome.

Rapid endocrine disruption: environmental estrogen actions triggered outside the nucleus.

An exogenous substance is defined as an endocrine disrupter chemical (EDC) if it alters the function of the endocrine system provoking adverse health effects. Environmental estrogens are the most studied EDCs. They follow the same mechanisms of action as the gonadal hormone 17beta-estradiol. Up to now, the estrogenicity of environmental estrogenic pollutants has been based on the property of these compounds to bind to estrogen receptors (ERs), either ERalpha or ERbeta, and to act subsequently as transcription factors when binding to the estrogen response element (ERE) in the DNA. All the estrogenic bioassays currently used are based on this mechanism of action. New evidence indicates that the definition of estrogenicity for a chemical should take into account other estrogen receptors as well as new signaling pathways. These include the activation of additional transcription factors as well as the action of xenoestrogens through estrogen receptors located outside the nucleus: in the plasma membrane, mitochondria and probably the cytosol. Therefore, new estrogenic bioassays should be developed to include the novel concept of rapid endocrine disruption.

Novel players in pancreatic islet signaling: from membrane receptors to nuclear channels.

Glucose and other nutrients regulate many aspects of pancreatic islet physiology. This includes not only insulin release, but also insulin synthesis and storage and other aspects of beta-cell biology, including cell proliferation, apoptosis, differentiation, and gene expression. This implies that in addition to the well-described signals for insulin release, other intracellular signaling mechanisms are needed. Here we describe the role of global and local Ca(2+) signals in insulin release, the regulation of these signals by new membrane receptors, and the generation of nuclear Ca(2+) signals involved in gene expression. An integrated view of these pathways should improve the present description of the beta-cell biology and provide new targets for novel drugs.

Low doses of bisphenol A and diethylstilbestrol impair Ca2+ signals in pancreatic alpha-cells through a nonclassical membrane estrogen receptor within intact islets of Langerhans.

Glucagon, secreted from pancreatic alpha-cells integrated within the islets of Langerhans, is involved in the regulation of glucose metabolism by enhancing the synthesis and mobilization of glucose in the liver. In addition, it has other extrahepatic effects ranging from lipolysis in adipose tissue to the control of satiety in the central nervous system. In this article, we show that the endocrine disruptors bisphenol A (BPA) and diethylstilbestrol (DES), at a concentration of 10(-9) M, suppressed low-glucose-induced intracellular calcium ion ([Ca2+]i) oscillations in alpha-cells, the signal that triggers glucagon secretion. This action has a rapid onset, and it is reproduced by the impermeable molecule estradiol (E2) conjugated to horseradish peroxidase (E-HRP). Competition studies using E-HRP binding in immunocytochemically identified alpha-cells indicate that 17beta-E2, BPA, and DES share a common membrane-binding site whose pharmacologic profile differs from the classical ER. The effects triggered by BPA, DES, and E2 are blocked by the G alpha i- and G alpha o-protein inhibitor pertussis toxin, by the guanylate cyclase-specific inhibitor 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one, and by the nitric oxide synthase inhibitor N-nitro-L-arginine methyl ester. The effects are reproduced by 8-bromo-guanosine 3',5'-cyclic monophosphate and suppressed in the presence of the cGMP-dependent protein kinase inhibitor KT-5823. The action of E2, BPA, and DES in pancreatic alpha-cells may explain some of the effects elicited by endocrine disruptors in the metabolism of glucose and lipid.

A nonclassical estrogen membrane receptor triggers rapid differential actions in the endocrine pancreas.

Glucose homeostasis in blood is mainly maintained by insulin released from beta-cells and glucagon released from alpha-cells, both integrated within the pancreatic islet of Langerhans. The secretory processes in both types of cells are triggered by a rise in intracellular calcium concentration ([Ca2+](i)). In this study, rapid effects of the natural hormone E2 on [Ca2+](i) were studied in both types of cells within intact islets using laser scanning confocal microscopy. alpha- And beta-cells showed opposite [Ca2+](i) responses when stimulated with physiological concentrations of 17beta-E2. Although the estrogen produced an increase in the frequency of glucose-induced [Ca2+](i) oscillations in insulin-releasing beta-cells, it prevented the low glucose-induced [Ca2+](i) oscillations in glucagon-releasing alpha-cells. The effects of 17beta-E2 on alpha-cells were mimicked by the cGMP permeable analog 8bromo-cGMP and blocked by the cGMP-dependent protein kinase (PKG) inhibitor KT5823. Evidence indicated that these were membrane actions mediated by a nonclassical ER. Both effects were rapid in onset and were reproduced by 17beta-E2 linked to horseradish peroxidase, a cell-impermeable molecule. Furthermore, these actions were not blocked by the specific ER blocker ICI 182,780. Competition studies performed with 17beta-E2 linked to horseradish peroxidase binding in alpha-cells supported the idea that the membrane receptor involved is neither ERalpha nor ERbeta. Additionally, the binding site was shared by the neurotransmitters epinephrine, norepinephrine, and dopamine and had the same pharmacological profile as the receptor previously described for beta-cells. Therefore, rapid estrogen actions in islet cells are initiated by a nonclassical estrogen membrane receptor.

Estrogen and xenoestrogen actions on endocrine pancreas: from ion channel modulation to activation of nuclear function.

17beta-Estradiol elicits a rapid opposite effect on [Ca2+]i in alpha- and beta-cells within intact islets of Langerhans. In beta-cells, physiological concentrations of the gonadal hormone decreases KATP channel activity in synergy with glucose, leading to a membrane depolarization that opens voltage-gated Ca2+ channels, potentiating Ca2+ signals. As a consequence insulin release is enhanced and transcription factor CREB is activated in a Ca(2+)-dependent manner. In glucagon-containing alpha-cells, 17beta-estradiol provokes the abolishment of Ca2+ oscillations generated by low glucose, a situation that should decrease glucagon release. In both types of cells the second messenger involved is cGMP. The estrogen receptor involved is located in the plasma membrane and has a pharmacological profile unrelated to classical estrogen receptors ERalpha and ERbeta. For that reason, it has been named non-classical membrane estrogen receptor (ncmER). Although the physiological roles of this receptor are still unknown, it may be implicated in the responses of the endocrine pancreas to the physiological and pathological changes of 17beta-estradiol.

Negative neuronal differentiation of human adipose-derived stem cell clones.

AIMS: Adipose mesenchymal stem cells are a heterogeneous population. Therefore, the question posed in this study is whether the heterogenic differentiation potential exhibited by the different clones toward mesodermic lineages can be extended to nonmesodermic lineages, such as the neuroectoderm. MATERIALS & METHODS: Different single cell clones of human adipose mesenchymal stem cells from the same donor were isolated. Neuronal plasticity of the clones was assessed according to the pattern DNA methylation, gene expression and intracellular calcium responses. RESULTS: Under neurogenic culture conditions, clones presented variable expression of neuronal-specific genes, but still expressed osteogenic markers. No calcium response was exhibited in response to KCl incubation. The DNA methylation profile presented a very similar pattern in neuroectoderm gene promoters. CONCLUSIONS: Data indicate that there are no significant differences between the undifferentiated and supposedly neuronal-differentiated mesenchymal cells.

Antidiabetic actions of an estrogen receptor ß selective agonist.

The estrogen receptor ß (ERß) is emerging as an important player in the physiology of the endocrine pancreas. We evaluated the role and antidiabetic actions of the ERß selective agonist WAY200070 as an insulinotropic molecule. We demonstrate that WAY200070 enhances glucose-stimulated insulin secretion both in mouse and human islets. In vivo experiments showed that a single administration of WAY200070 leads to an increase in plasma insulin levels with a concomitant improved response to a glucose load. Two-week treatment administration increased glucose-induced insulin release and pancreatic ß-cell mass and improved glucose and insulin sensitivity. In addition, streptozotocin-nicotinamide-induced diabetic mice treated with WAY200070 exhibited a significant improvement in plasma insulin levels and glucose tolerance as well as a regeneration of pancreatic ß-cell mass. Studies performed in db/db mice demonstrated that this compound restored first-phase insulin secretion and enhanced pancreatic ß-cell mass. We conclude that ERß agonists should be considered as new targets for the treatment of diabetes.

Role of ERß and GPR30 in the endocrine pancreas: A matter of estrogen dose.

The endocrine pancreas has emerged as a target for estrogens. The functions of pancreatic α-, ß- and δ-cells are modulated by the endogenous hormone, 17ß-estradiol (E2). Low physiological concentrations (100pM-1nM) of E2 rapidly decrease the activity of the ATP-sensitive potassium channel (K(ATP)) and enhance glucose-induced insulin release in ß-cells in an estrogen receptor ß (ERß)-dependent manner. In addition to the insulinotropic action of ERß, the newly described estrogen receptor, GPR30, is involved in the insulinotropic effects of high doses of E2 (100nM-5µM). The specific GPR30 agonist G1 also increases insulin secretion in ß-cells. Low glucose-induced calcium oscillations and glucagon secretion are suppressed by E2. The effects on glucagon secretion may be mediated by GPR30. Somatostatin release is also decreased by E2 and G1. In this review we summarize all the data published up to date on the rapid insulinotropic effects of estrogens in the endocrine pancreas and propose a model to integrate the estrogen actions mediated through both receptors.

Insulinotropic effect of the non-steroidal compound STX in pancreatic ß-cells.

The non-steroidal compound STX modulates the hypothalamic control of core body temperature and energy homeostasis. The aim of this work was to study the potential effects of STX on pancreatic ß-cell function. 1-10 nM STX produced an increase in glucose-induced insulin secretion in isolated islets from male mice, whereas it had no effect in islets from female mice. This insulinotropic effect of STX was abolished by the anti-estrogen ICI 182,780. STX increased intracellular calcium entry in both whole islets and isolated ß-cells, and closed the K(ATP) channel, suggesting a direct effect on ß-cells. When intraperitoneal glucose tolerance test was performed, a single dose of 100 µg/kg body weight STX improved glucose sensitivity in males, yet it had a slight effect on females. In agreement with the effect on isolated islets, 100 µg/kg dose of STX enhanced the plasma insulin increase in response to a glucose load, while it did not in females. Long-term treatment (100 µg/kg, 6 days) of male mice with STX did not alter body weight, fasting glucose, glucose sensitivity or islet insulin content. Ovariectomized females were insensitive to STX (100 µg/kg), after either an acute administration or a 6-day treatment. This long-term treatment was also ineffective in a mouse model of mild diabetes. Therefore, STX appears to have a gender-specific effect on blood glucose homeostasis, which is only manifested after an acute administration. The insulinotropic effect of STX in pancreatic ß-cells is mediated by the closure of the K(ATP) channel and the increase in intracellular calcium concentration. The in vivo improvement in glucose tolerance appears to be mostly due to the enhancement of insulin secretion from ß-cells.

Regulation of K(ATP) channel by 17ß-estradiol in pancreatic ß-cells.

ATP-sensitive potassium channels (K(ATP)) regulate electrical activity and insulin secretion in pancreatic ß-cells. When glucose concentration increases, the [ATP]/[ADP] ratio rises closing K(ATP) channels, and the membrane potential depolarizes, triggering insulin secretion. This pivotal role of K(ATP) channels is used not only by glucose but also by neurotransmitters, hormones and other physiological agents to modulate electrical and secretory ß-cell response. In recent years, it has been demonstrated that estrogens and estrogen receptors are involved in glucose homeostasis, and that they can modulate the electrical activity and insulin secretion of pancreatic ß-cells. The hormone 17ß-estradiol (E2), at physiological levels, is implicated in maintaining normal insulin sensitivity for ß-cell function. Long term exposure to E2 increases insulin content, insulin gene expression and insulin release via the estrogen receptor α (ERα), while rapid responses to E2 can regulate K(ATP) channels increasing cGMP levels through the estrogen receptor ß (ERß) and type A guanylate cyclase receptor (GC-A). This review summarizes the main actions of 17ß-estradiol on K(ATP) channels and the subsequent insulin release in pancreatic ß-cells.

A water-soluble perylene dye functionalised with a 17ß-estradiol: a new fluorescent tool for steroid hormones.

We have successfully been able to synthesise a specific estrogen receptor-directed biolabel based on a fluorescent water-soluble perylenebisimide, thus offering great potential for determining the presence of estrogen receptors in any kind of cell. Moreover, this synthetic strategy allows the preparation of other conjugates involved in the study of any kind of receptor, simply by selecting the appropriate agonist or antagonist.