Assessing the impact of insect protein sources on intestinal health and disease: insights from human ex vivo and rat in vivo models.

The exploration of edible insects, specifically Alphitobius diaperinus and Tenebrio molitor, as sustainable sources of protein for human consumption is an emerging field. However, research into their effects on intestinal health, especially in relation to inflammation and permeability, remains limited. Using ex vivo and in vivo models of intestinal health and disease, in this study we assess the impact of the above insects on intestinal function by focusing on inflammation, barrier dysfunction and morphological changes. Initially, human intestinal explants were exposed to in vitro-digested extracts of these insects, almond and beef. Immune secretome analysis showed that the inflammatory response to insect-treated samples was comparatively lower than it was for samples exposed to almond and beef. Animal studies using yellow mealworm (Tenebrio molitor) and buffalo (Alphitobius diaperinus) flours were then used to evaluate their safety in healthy rats and LPS-induced intestinal dysfunction rats. Chronic administration of these insect-derived flours showed no adverse effects on behavior, metabolism, intestinal morphology or immune response (such as inflammation or allergy markers) in healthy Wistar rats. Notably, in rats subjected to proinflammatory LPS-induced intestinal dysfunction, T. molitor consumption did not exacerbate symptoms, nor did it increase allergic responses. These findings validate the safety of these edible insects under healthy conditions, demonstrate their innocuity in a model of intestinal dysfunction, and underscore their promise as sustainable and nutritionally valuable dietary protein sources.

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.

Role of hepatic peroxisome proliferator-activated receptor γ in non-alcoholic fatty liver disease.

Peroxisome proliferator-activated receptor γ (PPARγ) belongs to a family of nuclear receptors that could serve as lipid sensors. PPARγ is the target of a group of insulin sensitizers called thiazolidinediones (TZDs) which regulate the expression of genes involved in glucose and lipid metabolism as well as adipokines that regulate metabolic function in other tissues. Non-alcoholic fatty liver disease (NAFLD) has a high prevalence worldwide and is even higher in patients with obesity and insulin resistance. TZD-mediated activation of PPARγ could serve as a good treatment for NAFLD because TZDs have shown anti-fibrogenic and anti-inflammatory effectsin vitro and increase insulin sensitivity in peripheral tissues which improves liver pathology. However, mechanistic studies in mouse models suggest that the activation of PPARγ in hepatocytes might reduce or limit the therapeutic potential of TZD against NAFLD. In this review, we briefly describe the short history of PPAR isoforms, the relevance of their expression in different tissues, as well as the pathogenesis and potential therapeutics for NAFLD. We also discuss some evidence derived from mouse models that could be useful for endocrinologists to assess tissue-specific roles of PPARs, complement reverse endocrinology approaches, and understand the direct role that PPARγ has in hepatocytes and non-parenchymal cells.

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 Alphitobius 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. Glucagon-like peptide 1 (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. © 2022 The Authors. Journal of The Science of Food and Agriculture published by John Wiley & Sons Ltd on behalf of Society of Chemical Industry.

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.

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.

Grape-Seed Proanthocyanidin Extract Reverts Obesity-Related Metabolic Derangements in Aged Female Rats.

Obesity and ageing are current issues of global concern. Adaptive homeostasis is compromised in the elderly, who are more likely to suffer age-related health issues, such as obesity, metabolic syndrome, and cardiovascular disease. The current worldwide prevalence of obesity and higher life expectancy call for new strategies for treating metabolic disorders. Grape-seed proanthocyanidin extract (GSPE) is reported to be effective in ameliorating these pathologies, especially in young animal models. In this study, we aimed to test the effectiveness of GSPE in modulating obesity-related pathologies in aged rats fed an obesogenic diet. To do so, 21-month-old rats were fed a high-fat/high-sucrose diet (cafeteria diet) for 11 weeks. Two time points for GSPE administration (500 mg/kg body weight), i.e., a 10-day preventive GSPE treatment prior to cafeteria diet intervention and a simultaneous GSPE treatment with the cafeteria diet, were assayed. Body weight, metabolic parameters, liver steatosis, and systemic inflammation were analysed. GSPE administered simultaneously with the cafeteria diet was effective in reducing body weight, total adiposity, and liver steatosis. However, the preventive treatment was effective in reducing only mesenteric adiposity in these obese, aged rats. Our results confirm that the simultaneous administration of GSPE improves metabolic disruptions caused by the cafeteria diet also in aged rats.

A Ten-Day Grape Seed Procyanidin Treatment Prevents Certain Ageing Processes in Female Rats over the Long Term.

Adaptive homeostasis declines with age and this leads to, among other things, the appearance of chronic age-related pathologies such as cancer, neurodegeneration, osteoporosis, sarcopenia, cardiovascular disease and diabetes. Grape seed-derived procyanidins (GSPE) have been shown to be effective against several of these pathologies, mainly in young animal models. Here we test their effectiveness in aged animals: 21-month-old female rats were treated with 500 mg GSPE/kg of body weight for ten days. Afterwards they were kept on a chow diet for eleven weeks. Food intake, body weight, metabolic plasma parameters and tumor incidence were measured. The GSPE administered to aged rats had an effect on food intake during the treatment and after eleven weeks continued to have an effect on visceral adiposity. It prevented pancreas dysfunction induced by ageing and maintained a higher glucagon/insulin ratio together with a lower decrease in ketonemia. It was very effective in preventing age-related tumor development. All in all, this study supports the positive effect of GSPE on preventing some age-related pathologies.

Gastrointestinally Digested Protein from the Insect Alphitobius diaperinus Stimulates a Different Intestinal Secretome than Beef or Almond, Producing a Differential Response in Food Intake in Rats.

In this study we compare the interaction of three protein sources-insect, beef, and almond-with the gastrointestinal tract. We measured the enterohormone secretion ex vivo in human and pig intestine treated with in vitro digestions of these foods. Insect and beef were the most effective in inducing the secretion of CCK, while almond was the most effective in inducing PYY in pig duodenum. In the human colon, almond was also the most effective in inducing PYY, and GLP-1 levels were increased by insect and beef. The three digested proteins reduced ghrelin secretion in pig duodenum, while only insect reduced ghrelin secretion in human colon. We also found that food intake in rats increased in groups fed a raw insect pre-load and decreased when fed raw almond. In conclusion, the insect Alphitobius diaperinus modulates duodenal and colonic enterohormone release and increases food intake in rats. These effects differ from beef and almond.