Food intake modulation by insect protein through the interaction with the enteroendocrine system

Les proteïnes animals són les més esteses per al consum humà com a font de proteïna d'alta qualitat. A causa de la superpoblació mundial, s'espera que la seva demanda augmenti a nivell mundial en els propers anys. Tanmateix, la producció de carn té nombroses implicacions negatives per al medi ambient. Així, la recerca de noves fonts de proteïnes produïdes respectuoses amb el medi ambient és prioritaria. Els insectes s'han caracteritzat com una bona font de proteïnes d'alta qualitat, que contenen una quantitat d’altres nutrients. Tot i que s'han caracteritzat molts efectes beneficiosos sobre la salut, la informació sobre la seva bioactivitat a nivell intestinal es disposa escasseja. Per tant, en aquesta tesi hem volgut caracteritzar la capacitat de la proteïna d'insecte per modular la secreció d'enterohormones i la posterior ingesta d'aliments, comparant-la amb fonts de proteïnes tradicionals. Vam demostrar que la proteïna d'insecte, d'Alphitobius diaperinus, modula la secreció d'enterohormonas ex vivo en l’intestiní produint un perfil secretor diferent de l'obtingut amb ametlla i vedella. Quan les diferents fonts de proteïnes es van administrar de manera aguda a rates, vam observar que la ingesta d'aliments del grup d'insecte augmentava en comparació amb els grups d'ametlla i vedella. Aquest augment d’ingesta d'aliments es va perdre després d'una setmana de tractament. El mateix va passar amb Tenebrio molitor, indicant així que l'efecte observat no era específic de l'espècie. En humans, l'administració d'una precàrrega de proteïne de l'insecte A. diaperinus va modular la ingesta d'aliments de manera similar l’ametlla. Vam observar un augment de la ingesta de proteïne després de les dues precàrregues amb un menor augment de la ingesta d'energia després de la precàrrega de d'insecte. En conclusió, la proteïna d'insecte és un candidat prometedor per ser considerat com un ingredient bioactiu destinat a persones que necessiten augmentar la seva ingesta d'aliments.La proteína animal es la más extendida para consumo humano como fuente proteica de alta calidad. Debido a la sobrepoblación mundial, se espera que su demanda aumente globalmente en los próximos años. Sin embargo, la producción de carne conlleva numerosas implicaciones negativas para el medio ambiente. Por lo tanto, la búsqueda de fuentes alternativas de proteína respetuosas con el medio ambiente es prioritaria. Los insectos se han caracterizado como fuente de proteína de alta calidad y contienen una cantidad significativa de otros nutrientes. Aunque se han caracterizado muchos efectos beneficiosos para la salud, la información sobre bioactividad a nivel intestinal escasea. Por lo tanto, en esta tesis nos propusimos caracterizar la capacidad de la proteína de insecto para modular la secreción de enterohormonas y la posterior ingesta, comparándola con fuentes de proteína tradicionales. Demostramos que la proteína de insecto, procedente de Alphitobius diaperinus, puede modular la secreción de enterohormonas ex vivo en intestino produciendo un perfil secretorio diferente al obtenido con almendra y ternera. Cuando estas fuentes de proteína se administraron de forma aguda a ratas, observamos que la ingesta del grupo insecto aumentó en comparación con los grupos almendra y ternera. Este aumento en la ingesta se perdió después de una semana de tratamiento. Lo mismo ocurrió con Tenebrio molitor, por lo que el efecto observado no fue específico de especie. En humanos, la administración de una precarga de proteína del insecto A. diaperinus moduló la ingesta de manera similar a la almendra. Observamos un aumento en la ingesta de proteína después de ambas precargas con un menor aumento en la ingesta de energía después de la precarga de insecto. En conclusión, la proteína de insecto es un candidato prometedor para ser considerado como un ingrediente bioactivo destinado a las personas que necesitan aumentar su ingesta.Nowadays, animal protein and derived products are the most extended ones for human consumption as high-quality protein sources. Due to the overpopulation that the world is facing, its demand is expected to increase globally in the next years. However, meat production carries numerous negative implications for the environment. For this reason, the search for alternative environmentally friendly produced protein sources is becoming more important. Insects have been characterized as a good source of high-quality protein, also containing a significant amount of good quality fats, minerals and vitamins. Although many beneficial effects on health have been characterized, scarce information is available about their bioactivity at the intestinal level. Hence, in this thesis we aimed to characterize the ability of the insect protein to modulate the enterohormone secretion and subsequent food intake, comparing it with more traditional protein sources, and to determine if it can have long-term effects on this enteroendocrine function. We showed that insect protein, from Alphitobius diaperinus, can modulate the enterohormone secretion ex vivo in intestinal samples producing secretory profile with some differences compared with the secretome obtained from almond and beef proteins. Some of the secretions have been related to the amino acid composition of the respective protein sources. When the different protein sources were acutely administered to rats, we observed that the food intake from the insect group was increased compared with the almond and beef groups, although the protein dose was adjusted for the three treatments. After a chronic administration, this increase in food intake was lost after a week of treatment. The same occurred with Tenebrio molitor, which meant that the observed effect was not species-specific. In human subjects, the administration of a protein preload from the insect A. diaperinus modulated food intake similarly to an almond preload. We observed an increased protein intake after both preloads with a lower increase in energy intake after the insect protein preload. In conclusion, insect protein is a promising candidate to be considered as a bioactive ingredient intended for people who need to increase their food intake

Differential effects of a cafeteria diet and GSPE preventive treatments on the enterohormone secretions of aged vs. young female rats

Grape seed derived procyanidins (GSPE) have been shown to effectively prevent intestinal disarrangements induced by a cafeteria diet in young rats. However, little is known about the effects of procyanidins and cafeteria diet on enterohormone secretion in aged rats, as the ageing processes modify these effects. To study these effects in aged rats, we subjected 21-month-old and young 2-month-old female rats to two sub-chronic preventive GSPE treatments. After three months of cafeteria diet administration, we analysed the basal and stimulated secretion and mRNA expression of CCK, PYY and GLP-1, caecal SCFA and intestinal sizes. We found that the effects of a cafeteria diet on the basal duodenal CCK secretion are age dependent. GLP-1 in the ileum was not modified regardless of the rat's age, and GSPE preventive effects differed in the two age groups. GSPE pre-treatment reduced GLP-1, PYY and ChgA in mRNA in aged ileum tissue, while the cafeteria diet increased these in aged colon. The GSPE treatments only modified low-abundance SCFAs. The cafeteria diet in aged rats increases the caecum size differently from that in young rats and GSPE pre-treatment prevents this increase. Therefore, ageing modifies nutrient sensing, and the cafeteria diet acts mainly on the duodenum and colon, while procyanidins have a larger effect on the ileum.info:eu-repo/semantics/publishedVersio

Modulation of food intake by differential TAS2R stimulation in rat

Metabolic surgery modulates the enterohormone profile, which leads, among other effects, to changes in food intake. Bitter taste receptors (TAS2Rs) have been identified in the gastrointestinal tract and specific stimulation of these has been linked to the control of ghrelin secretion. We hypothesize that optimal stimulation of TAS2Rs could help to modulate enteroendocrine secretions and thus regulate food intake. To determine this, we have assayed the response to specific agonists for hTAS2R5, hTAS2R14 and hTAS2R39 on enteroendocrine secretions from intestinal segments and food intake in rats. We found that hTAS2R5 agonists stimulate glucagon-like peptide 1 (GLP-1) and cholecystokinin (CCK), and reduce food intake. hTAS2R14 agonists induce GLP1, while hTASR39 agonists tend to increase peptide YY (PYY) but fail to reduce food intake. The effect of simultaneously activating several receptors is heterogeneous depending on the relative affinity of the agonists for each receptor. Although detailed mechanisms are not clear, bitter compounds can stimulate differentially enteroendocrine secretions that modulate food intake in rats

Effect of an Acute Insect Preload vs. an Almond Preload on Energy Intake, Subjective Food Consumption and Intestinal Health in Healthy Young Adults

Protein is considered the most satiating macronutrient, and its effect on satiety and food intake is source-dependent. For the first time, we compared the effect of the administration of an insect or almond preload, both containing 20 g of protein, on appetite and food intake in human subjects. Participants consumed both foods and a vehicle as a liquid preload on three separate days. They were then offered a breakfast and lunch buffet meal at which food intake was measured. Visual analogue scale (VAS) questionnaires were completed following the three preloads to assess appetite and other sensations. At breakfast, reduced energy intake was observed for both preloads compared with vehicle. At lunch, food intake only differed in the insect group, which consumed more than the vehicle. Insect preload increased the total amount of protein ingested with a slight increase in total energy consumed, differently than almond, which significantly increased total protein and energy consumed. There was no correlation between indigestion-sensation ratings and food intake. Moreover, the insect preload resulted in lower sleepiness and tiredness ratings compared with the almond preload. Thus, insect-derived protein may be suitable as a safe ingredient for snacks intended for elderly or infirm patients who require increased protein intake

Effect of an Acute Insect Preload vs. an Almond Preload on Energy Intake, Subjective Food Consumption and Intestinal Health in Healthy Young Adults

Protein is considered the most satiating macronutrient, and its effect on satiety and food intake is source-dependent. For the first time, we compared the effect of the administration of an insect or almond preload, both containing 20 g of protein, on appetite and food intake in human subjects. Participants consumed both foods and a vehicle as a liquid preload on three separate days. They were then offered a breakfast and lunch buffet meal at which food intake was measured. Visual analogue scale (VAS) questionnaires were completed following the three preloads to assess appetite and other sensations. At breakfast, reduced energy intake was observed for both preloads compared with vehicle. At lunch, food intake only differed in the insect group, which consumed more than the vehicle. Insect preload increased the total amount of protein ingested with a slight increase in total energy consumed, differently than almond, which significantly increased total protein and energy consumed. There was no correlation between indigestion-sensation ratings and food intake. Moreover, the insect preload resulted in lower sleepiness and tiredness ratings compared with the almond preload. Thus, insect-derived protein may be suitable as a safe ingredient for snacks intended for elderly or infirm patients who require increased protein intake

GSPE Pre-Treatment Exerts Long-Lasting Preventive Effects against Aging-Induced Changes in the Colonic Enterohormone Profile of Female Rats

The impact that healthy aging can have on society has raised great interest in understanding aging mechanisms. However, the effects this biological process may have on the gastrointestinal tract (GIT) have not yet been fully described. Results in relation to changes observed in the enteroendocrine system along the GIT are controversial. Grape seed proanthocyanidin extracts (GSPE) have been shown to protect against several pathologies associated with aging. Based on previous results, we hypothesized that a GSPE pre-treatment could prevent the aging processes that affect the enteroendocrine system. To test this hypothesis, we treated 21-month-old female rats with GSPE for 10 days. Eleven weeks after the treatment, we analyzed the effects of GSPE by comparing these aged animals with young animals. Aging induced a greater endocrine response to stimulation in the upper GIT segments (cholecystokinin (CCK) and glucagon-like peptide-1 (GLP-1)), a decrease in the mRNA abundance of GLP-1, peptide YY (PYY) and chromogranin A (ChgA) in the colon, and an increase in colonic butyrate. GSPE-treated rats were protected against a decrease in enterohormone expression in the colon. This effect is not directly related to the abundance of microbiome or short-chain fatty acids (SCFA) at this location. GSPE may therefore be effective in preventing a decrease in the colonic abundance of enterohormone expression induced by aging

Effects of grape seed proanthocyanidin extract on lipopolysaccharide translocation and trafficking from the gut to tissues

Diet-associated alterations of the intestinal barrier and gut microbiota promote intestinal lipopolysaccharide (LPS) translocation from the lumen to the lamina propria through different pathways, leading to an increase in LPS levels in the plasma known as metabolic endotoxemia.As a pharmacological dose of grape seed proanthocyanidin extract (GSPE) can reduce metabolic endotoxemia of obese rats, in the current study, we aimed to evaluate GSPE modulation of LPS translocation and the underlying mechanisms. We performed both an in vitro experiment with Caco-2 cells and an in vivo experiment with Wistar female rats fed a cafeteria (CAF) diet. GSPE was effective in regulating intestinal permeability through the modulation of receptor-mediated endocytosis pathway, as well as the gut microbiota interaction with the endocannabinoid system through epigenetic mechanisms. Our results confirm that GSPE can ameliorate intestinal dysfunction and metabolic endotoxemia caused by an excess of dietary lipids by modulating the endotoxin-translocation pathways

Administration of Alphitobius diaperinus or Tenebrio molitor before meals transiently increases food intake through enterohormone regulation in female rats

Background. It has been previously shown that acutely administered insect A. diaperinus protein increases food intake in rats and modifies the ex vivo enterohormone secretory profile differently than beef or almond proteins. In this study, we aimed to evaluate whether these effects could be maintained for a longer period and determine the underlying mechanisms. Results. We administered two different insect species to rats for 26 days and measured food intake at different time points. Both insect species increased food intake in the first week, but the effect was later lost. GLP-1 and ghrelin were measured in plasma and ex vivo, and no chronic effects on their secretion or desensitization were found. Nevertheless, digested A. diaperinus acutely modified GLP-1 and ghrelin secretion ex vivo. Conclusion. Our results suggest that increases in food intake could be explained by a local ghrelin reduction acting in the small intestine.info:eu-repo/semantics/acceptedVersio