Female mice exposed to varying ratios of stearic to palmitic acid in a high-fat diet during gestation and lactation shows differential impairments of beta-cell function

Abstract

Aims

While emerging evidence implicates an abnormal stearic-to-palmitic acid ratio in saturated fats in beta-cell dysfunction, their gestational/lactational impacts remain underexplored. This study evaluates the differential transient and long-lasting effects of high-fat diets with contrasting stearic-to-palmitic acid ratios on maternal beta-cell function.

Materials and methods

Female mice were fed high-fat diets with high/low stearic-to-palmitic acid ratios during gestation/lactation, followed by a recovery period and subsequent exposure to an obesogenic diet. Beta-cell function was assessed using ex-vivo glucose-stimulated insulin secretion (GSIS) and immunohistochemistry. Islets mRNA profiling was performed using RNA-sequencing.

Key findings

Both high- and low-ratio groups showed impaired GSIS post-lactation. High-ratio-fed dams exhibited pronounced compensatory responses, including increased islet size, number, and elevated Stx1a, Stx4, Pdx1, Mafa expression. Following metabolic re-challenge, high-ratio group demonstrated more severely impaired ex vivo insulin release. No significant differences in islet apoptosis and senescence were observed between the two groups. Transcriptomic profiling, however, revealed distinct mechanistic pathways: the high-ratio diet was likely to disrupt beta-cell organelles ultrastructure, while the low-ratio diet predominantly dysregulated chemokine-mediated immune signaling networks.

Significance

Gestational/lactational exposure to high-fat diets with both high and low ratios of stearic-to-palmitic acid exerts pronounced transient impacts on beta-cell function, with the high-ratio diet inducing more severe and persistent detrimental effects. These findings highlight the critical influence and importance of dietary saturated fatty acid composition in maternal metabolic programming and beta-cell vulnerability.