ORIGINAL RESEARCH article
Front. Nutr.
Sec. Nutrition Methodology
Effects of maternal overnutrition and metabolic challenge in adult life on the histological integrity of the liver and intestinal epithelium in rabbits
Provisionally accepted
Lucía Carolina Cano1Erika Navarrete1Pedro Medina1,2Juan Pablo Ochoa-Romo1Georgina Díaz1
Rodrigo Montúfar-Chaveznava3
Rosa María Vigueras2
Ivette Caldelas4*- 1Universidad Nacional Autonoma de Mexico Instituto de Investigaciones Biomedicas, Mexico City, Mexico
- 2Instituto Nacional de Pediatria, Mexico City, Mexico
- 3Universidad Camilo José Cela, Escuela Politécnica Superior de Tecnología y Ciencia, Madrid, Spain
- 4University School of Design, Innovation and Technology (ESNE), Madrid, Spain
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Introduction: Maternal overnutrition during critical stages of embryonic development has been implicated as a major determinant of developmental and metabolic disturbances in offspring. Current data concerning how perinatal exposure to high-fat and high-carbohydrate diets, followed by re-exposure in adulthood (metabolic challenge), affects the metabolic regulation and structural integrity of the liver and small intestine, key organs of the gut-liver axis (GLA). Methods: Female rabbits were fed either a standard diet (SD) or a high-fat and high-carbohydrate diet (HFCD) before mating and during gestation. The offspring at postnatal day 440 were challenged with a HFCD or SD for 30 days and assigned to the following groups: the SD-SD group (obtained from does fed SD and challenged with SD), SD-HFCD group, HFCD-SD group and HFCD-HFCD group. After completion of the metabolic challenge, glucose, total cholesterol, low-and high-density lipoproteins, free fatty acids and triglycerides, gamma-glutamyl transferase, bilirubin, aminotransferases and the level of lipopolysaccharides (LPS) were measured. Additionally, histological analysis of the liver and duodenum were conducted using several staining methods. Results: At both metabolic and histopathological levels, rabbits exposed to HFCD during adulthood exhibited more pronounced alterations. In particular, the HFCD-HFCD group showed the greatest degree of impairment. Moreover, morphological changes were notably more severe in duodenal tissue compared to liver tissue. Discussion: These results indicate that exposure to an HFCD during critical developmental windows—both gestation and adulthood—induces significant metabolic disturbances and histological damage in the liver and intestinal epithelium. These effects appear to depend on the timing and duration of dietary exposure.
Keywords: maternal overnutrition, intestinal epithelium, tissue damage markers, Metabolic impairments, high-fat diet, High-carbohydrate diet
Received: 01 Sep 2025; Accepted: 19 Nov 2025.
Copyright: © 2025 Cano, Navarrete, Medina, Ochoa-Romo, Díaz, Montúfar-Chaveznava, Vigueras and Caldelas. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Ivette Caldelas, ivette.caldelas@udit.es
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