OGTT-Evoked Neuromedin U Response and Gastrointestinal Pattern of Regional mRNA Expression in MSG-Induced Obesity in Rats.

BACKGROUND: Neuromedin U (NMU) is a neuropeptide broadly expressed in the gastrointestinal (GI) tract and central nervous system (CNS), implicated in energy balance and glucose homeostasis. Recent studies have suggested that NMU may act as a "decretin" hormone by inhibiting glucose-stimulated insulin secretion (GSIS); however, in vivo findings remain inconclusive. This study evaluated plasma NMU responses during an oral glucose tolerance test (OGTT) and regional intestinal NMU expression in a monosodium glutamate (MSG)‑induced hypothalamic obesity (MHO) model in rats. METHODS: Thirty male Wistar rats were divided into control and MHO groups. MHO was induced by subcutaneous MSG injections during the neonatal period. After five months, metabolic parameters, oral glucose tolerance test (OGTT), plasma NMU levels, and NMU mRNA expression in the duodenum, jejunum, and ileum were analyzed using ELISA and RT-qPCR. RESULTS: The MHO group exhibited elevated fasting glucose, decreased basal insulin levels, and increased abdominal adiposity compared to controls, indicating a metabolically obese phenotype in this model. Basal plasma NMU levels were similar between groups. At 60 minutes post-glucose load, plasma NMU decreased significantly relative to baseline in both groups, with no difference between MHO and control rats. Intestinal NMU expression followed a proximal-to-distal declining pattern, consistent with previous reports, and did not differ between MHO and control rats. CONCLUSION: These findings suggest that NMU expression within the gastrointestinal tract remains regionally regulated and unaltered in experimental obesity. Furthermore, the significant decline in plasma NMU at 60 minutes is compatible with modulation during hyperglycemia but does not establish a causal role in glucose regulation. This pattern appears to be preserved in the MHO model despite metabolic dysfunction. Future studies employing receptor inhibition or NMU administration are warranted to elucidate its physiological role in insulin regulation.