Glucagon-like Peptide-1 Receptor in the Human Hypothalamus Is Associated with Body Mass Index and Colocalizes with the Anorexigenic Neuropeptide Nucleobindin-2/Nesfatin-1

• Published in: International journal of molecular sciences 2022-11, Vol.23 (23), p.14899
• Main Authors: Psilopanagioti, Aristea, Nikou, Sofia, Logotheti, Souzana, Arbi, Marina, Chartoumpekis, Dionysios V, Papadaki, Helen
• Format: Article
• Language: English
• Subjects: Animals; Antibodies; Apoptosis; Arcuate Nucleus of Hypothalamus - metabolism; Astrocytes; Autopsies; Body Mass Index; Body size; Brain; Diabetes; Energy balance; Feeding behavior; Food; Forebrain; Forebrain (basal); Glial fibrillary acidic protein; Glucagon; Glucagon-like peptide 1; Glucagon-Like Peptide-1 Receptor - metabolism; Hedonic response; Homeostasis; Humans; Hypothalamus; Hypothalamus (lateral); Hypothalamus - metabolism; Immunofluorescence; Immunohistochemistry; Luteinizing hormone; Metabolism; Nervous system; Neuronal-glial interactions; Neuropeptides; Neuropeptides - metabolism; Overweight; Pancreas; Peptides; Protein expression; Proteins; Reinforcement; Signal transduction
• ISSN: 1422-0067; 1661-6596; 1422-0067
• DOI: 10.3390/ijms232314899

Data on animals emphasize the importance of the neuronal glucagon-like peptide-1 (GLP-1) receptor (GLP-1R) for feeding suppression, although it is unclear whether astrocytes participate in the transduction of anorectic GLP-1R-dependent signals. In humans, the brain circuitry underlying these effects remains insufficiently investigated. The present study aimed to explore GLP-1R protein expression in the human hypothalamus and its correlation with body mass index (BMI). Sections of hypothalamus from 28 autopsy cases, 11 with normal weight (BMI < 25 kg/m2) and 17 with non-normal weight (BMI ≥ 25 kg/m2), were examined using immunohistochemistry and double immunofluorescence labeling. Prominent GLP-1R immunoexpression was detected in neurons of several hypothalamic nuclei, including paraventricular, supraoptic, and infundibular nuclei; the lateral hypothalamic area (LH); and basal forebrain nuclei. Interestingly, in the LH, GLP-1R was significantly decreased in individuals with BMI ≥ 25 kg/m2 compared with their normal weight counterparts (p = 0.03). Furthermore, GLP-1R was negatively correlated (τb = −0.347, p = 0.024) with BMI levels only in the LH. GLP-1R extensively colocalized with the anorexigenic and antiobesogenic neuropeptide nucleobindin-2/nesfatin-1 but not with the astrocytic marker glial fibrillary acidic protein. These data suggest a potential role for GLP-1R in the regulation of energy balance in the human hypothalamus. In the LH, an appetite- and reward-related brain region, reduced GLP-1R immunoexpression may contribute to the dysregulation of homeostatic and/or hedonic feeding behavior. Possible effects of NUCB2/nesfatin-1 on central GLP-1R signaling require further investigation.