INTRAUTERINE GROWTH RESTRICTION INDUCES INCREASED ASTROCYTIC AND NEURONAL O-GLYCOSYLATION IN HYPOTHALAMIC NUCLEI ON ADULT OFFSPRING

Intrauterine growth restriction(IUGR) is associated with the development of obesity, hypothalamic dysfunction, and impaired glucose metabolism. Protein O-glycosylation with N-acetylglucosamine(O-GlcNAc), a glucose-dependent post-translational modification, may influence hypothalamic energy balance. This study evaluated the density of O-GlcNAc-modified proteins and their colocalization with neuronal(NeuN) and astrocytic(GFAP) markers in the arcuate(ARC), lateral(LH), and ventromedial(VMH) hypothalamic nuclei, as well as food intake in IUGR offspring.
During gestation, female Wistar rats on caloric restriction(RG) received 50%of control intake(CG). At 90 days, male pups(n=3/group) were anesthetized, perfused, brains collected, frozen, and sectioned(30 μm). Sections were incubated with primary antibodies(anti-O-GlcNAc, anti-NeuN, anti-GFAP), secondary antibodies(AlexaFluor568, AlexaFluor488), imaged by confocal microscopy. Food intake assessed weekly; fluorescence quantified with ImageJ; Student’s t-test applied.
The RG group exhibited increased colocalization of O-GlcNAc with GFAP in the ARC and VMH(p<0.001), accompanied by reduced astrocytic labeling in these regions(p≤0.05). In the LH, higher colocalization of O-GlcNAc with NeuN(p=0.01) and increased O-GlcNAc labeling(p<0.05) were observed. Reduced NeuN labeling was detected in the ARC and LH(p<0.01). RG offspring showed lower food intake during the 1st, 3rd(p<0.001), 5th, and 6th(p<0.05) weeks after weaning, with intake comparable to CG from the 7th week onward.
IUGR induces increased neuronal and astrocytic O-glycosylation in specific hypothalamic nuclei involved in energy balance, accompanied by reduced labeling of these functional cells and normalization of food intake. These findings suggest alterations in cellular signaling that may impair hypothalamic homeostasis and contribute to obesity. O-GlcNAc may represent a key mechanism linking IUGR to late-onset obesity in offspring.