Dietary-induced perturbation of glucose clearance, glial function, and blood-brain barrier permeability, indepentent of adiposity

Authors: Thorson, Jennifer; FREETLY, HARVEY - Retired ARS Employee; Crouse, Matthew; Neville, Bryan; Oliver, William; Lindholm-Perry, Amanda; PREZOTTO, LIGIA - University Of Nebraska

Submitted to: Journal of the Endocrine Society
Publication Type: Abstract Only
Publication Acceptance Date: 3/27/2025
Publication Date: N/A
Citation: N/A

Interpretive Summary:

Technical Abstract: Glial cells contribute to the regulation of energy balance and metabolic pathologies, but are also sensitive to each. Nutritionally-induced alterations in blood-brain barrier structure and neuronal expression have detrimental influences on neuroendocrine physiological processes. These alterations are especially germane in regions proximal to circumventricular organs as they have the greatest potential to be influenced by dietary-induced insults. It is believed that diets high in starch contribute to systemic inflammation associated with increased adiposity that then impair blood-brain barrier and ultimately neuronal function. However, peripheral markers of diet-induced glial dysfunction have not been assessed to evaluate damage attributed to the diet over time. The calcium-binding protein S100B is primarily derived from glial cells. When glial cells are damaged, S100B is released from glial cells and allowed to diffuse into the peripheral circulation across a compromised blood-brain barrier. Here within, we offered one of two isocaloric diets to bovine peripubertal females (n = 8/diet). At week 0, females were offered a common basal diet rich in fiber. Over the next 6 weeks, half of the females transitioned to the elevated diet that consisted primarily of starch. By week 6 dietary transitions were complete, females then remained on the divergent diets for an additional 6 weeks. Blood was collected and subcutaneous adiposity via ultrasonography assessed at 0, 6, and 12 weeks. Glucose tolerance tests were performed at weeks 0, 6, and 12. We hypothesized that a starch-rich diet would increase peripherally circulating concentrations of S100B, independent of adiposity. As expected, body weight of growing females increased over time (P = 0.003), but did not differ by diet (P = 0.36). Divergent dietary treatments failed to induce differences in subcutaneous adiposity (P = 0.58), but the rate of glucose clearance was increased in females offered the elevated diet (P = 0.05). Circulating concentrations of S100B in females offered the basal diet remained unchanged over the course of the dietary trial (P = 0.37). However, females offered the elevated diet exhibited an increase in circulating concentrations of S100B from week 6 to 12 (P = 0.04). From these results we infer that both the glial cells are damaged and the blood-brain barrier impaired as a result of dietary-induced, glucose-regulated mechanisms, even in the absence of differences in adiposity. The rapid clearance of glucose in females offered the elevated diet potentially generates a cyclic, feed-forward insult on the central nervous system driven by repeated feeding bouts. These findings illustrate the importance of dietary composition during the developmental period as it pertains to central mechanisms that regulate metabolic health and ultimately the development of pathologies.