Effects of maternal overnutrition and metabolic challenge in adult life on the histological integrity of the liver and intestinal epithelium in rabbits.

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), are limited.

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 on postnatal day 440 were challenged with an HFCD or SD for 30 days and assigned to the following groups: SD-SD (obtained from does fed SD and challenged with SD), SD-HFCD, HFCD-SD, and HFCD-HFCD. After completion of the metabolic challenge, glucose, total cholesterol, low- and high-density lipoproteins, free fatty acids, triglycerides, gamma-glutamyl transferase, bilirubin, aminotransferases, and the level of lipopolysaccharides (LPS) were measured. Additionally, histological analysis of the liver and duodenum was 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 the duodenal tissue than in the 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.