Sex-based differences in the enteroendocrine system and food intake regulation due to dietary protein replacement by Alphitobius Diaperinus in rats

The rising global demand for animal protein, coupled with the environmental impact of conventional livestock, has sparked interest in sustainable alternatives. Insect-derived proteins, particularly from Alphitobius diaperinus (lesser mealworm), offer high nutritional value, good digestibility, and a minimal ecological footprint. Enteroendocrine hormones such as ghrelin, peptide YY (PYY), cholecystokinin (CCK), and glucagon-like peptide-1 (GLP-1) are key regulators of appetite, satiety, and energy homeostasis, responding dynamically to the composition and quality of ingested nutrients. Given the increasing prevalence of protein malnutrition in aging population and the metabolic challenges posed by obesogenic diets, this study aimed to investigate whether the enteroendocrine-modulating effects previously observed with acute A. diaperinus administration are sustained when utilized as the sole dietary protein source. Furthermore, we evaluated sex-specific responses under both standard and high-fat diet conditions in rats. Our findings demonstrate that A. diaperinus-based diets can alter caloric intake and elicit differential enteroendocrine secretion patterns depending on the sex and metabolic status of the animal, suggesting context-specific regulatory effects on energy balance and gut hormone responses. Together, these results enhance our understanding of how insect-based proteins interact with nutrient-sensing pathways and may inform the development of targeted nutritional strategies to support healthy aging, metabolic health, and environmental sustainability.