Maternal high-fat diet exposure impairs LKB1-TGFβ1 inflammatory pathway and increases hypothalamic 5HT receptors gene expression and somatic growth in young rats

The serotonergic system regulates various psychobiological processes, including neurodevelopment, mood, and feeding behavior. Maternal exposure to a high-fat diet (HFD) increases circulating proinflammatory cytokines, impairing the development of the serotonergic system in the offspring’s brain. The effects of maternal exposure to HFD on the offspring’s feeding behavior, somatic growth, and hypothalamic serotonergic system were investigated. Wistar rat offspring from HFD-fed dams displayed increased body weight, fat mass, and somatic growth but no changes in food intake or feeding behavior. They also showed elevated total cholesterol and reduced serum creatinine. At the molecular level, increased hypothalamic gene expression of Htr1a, Htr2a, and Tgfb1, along with a reduction in the phosphorylation of FoxO1^Thr24, cAMP response element-binding protein (CREB^Ser133), and liver kinase B1 (LKB1^Ser428) were observed. No differences in leptin or insulin signaling were found. These results suggest an initial disruption in energy homeostasis mediated by the serotonergic system.