BRAIN REGULATION OF MATERNAL METABOLISM: A ROLE FOR CITED1 IN PREGNANCY AND GESTATIONAL DIABETES SUSCEPTIBILITY

Pregnancy requires major metabolic adjustments coordinated by the hypothalamus to support maternal energy needs and fetal development. The hypothalamus, and particularly melanocortin neurons such as proopiomelanocortin (Pomc) and agouti-related protein (AgRP), plays a central role in this realignment by integrating signals from metabolic and sex-steroid hormones, including leptin and estradiol. The transcriptional co-regulator Cited1 has recently emerged as a mediator of leptin-estradiol synergy in these circuits, yet its contribution to pregnancy-induced metabolic adaptations remains poorly understood. Using a nutritionally induced mouse model of gestational diabetes mellitus (GDM), we monitored maternal metabolic shifts with high-resolution phenotyping. From conception through early lactation, we quantified body weight, energy expenditure, food intake and respiratory exchange ratio. Preliminary results show that GDM dams display marked disruptions in circadian metabolic rhythms, including flattened oscillations in energy expenditure and impaired substrate utilization reflected by an altered respiratory exchange ratio. These changes were accompanied by evidence of suboptimal maternal–fetal nutrient allocation, including altered fetal growth patterns consistent with clinical GDM outcomes. To assess the role of Cited1, we selectively reduced its expression in the AgRP neurons using targeted viral approaches and confirmed effective, localized modulation. Placental Cited1 levels were also elevated in obese dams, suggesting broader involvement in maternal–fetal nutrient partitioning. Together, these findings provide one of the first functional indications that Cited1 contributes to the neuroendocrine adjustments supporting maternal metabolic adaptation and highlight its potential relevance to GDM vulnerability.