LCN2 blockade mitigating metabolic dysregulation and redefining appetite control in type 2 diabetes
Por:
Ernesto C.-M.S., Laura S.-S.D., Obed P.-M.I., David A.-G.R., Eloy G.-G.J., Lilia G.-H.A.
Publicada:
1 ene 2025
Resumen:
LCN2 has an osteokine important for appetite regulation; in type 2 diabetes (T2D) it is not known whether appetite regulation mediated by LCN2 in the brain is altered. In this work, we focus on exploring the role of blocking LCN2 in metabolic health and appetite regulation within the central nervous system of mice with T2D. MATERIAL AND METHODS: 4-week-old male C57BL/6 mice were used, divided into four experimental groups: intact, T2D, TD2/anti-LCN2, and T2D/IgG as isotype control. T2D was induced by low doses of streptozotocin and a high-carbohydrate diet. LCN2 blockade was performed by intraperitoneal administration of a polyclonal anti-LCN2 antibody. We analyzed metabolic parameters, food intake, feeding patterns, and serum LCN2 and leptin concentrations. In another group of intact or T2D mice, we analyzed the effect of blocking LCN2 and recombinant LCN2 on food consumption in a fasting-refeeding test and, the expression of cFOS and LCN2 in brain sections, specifically in the hypothalamus, piriform cortex, visceral area, arcuate nucleus and caudate-putamen. RESULTS: T2D caused an increase in serum LCN2, without alterations in Ad libitum feeding, but with changes in the feeding pattern associated with alterations in LCN2-cFOS signalling in hypothalamic and non-hypothalamic brain regions. Blocking LCN2 improved metabolic parameters, increased Ad libitum feeding, and restored the feeding pattern after fasting, which is associated with enhanced LCN2 signalling in the brain. CONCLUSIONS: Blocking LCN2 restores metabolic health and normalizes the pattern of food consumption by normalizing LCN2 signalling in different brain regions. © 2024. The Author(s).
Filiaciones:
Ernesto C.-M.S.:
Section of Osteimmunology and Oral Immunology, Laboratory of Dental Reseach. FES Iztacala, National Autonomous University of Mexico (UNAM), Mexico State, Mexico
Laura S.-S.D.:
Section of Osteimmunology and Oral Immunology, Laboratory of Dental Reseach. FES Iztacala, National Autonomous University of Mexico (UNAM), Mexico State, Mexico
Postgraduate in Dentistry Science, National Autonomous University of Mexico (UNAM), Mexico City, Mexico
Obed P.-M.I.:
Section of Sensation Neurobiology and Oral Movements, Laboratory of Dental Reseach. FES Iztacalaestigación Odontológica, National Autonomous University of Mexico (UNAM), Mexico
David A.-G.R.:
Section of Sensation Neurobiology and Oral Movements, Laboratory of Dental Reseach. FES Iztacalaestigación Odontológica, National Autonomous University of Mexico (UNAM), Mexico
Eloy G.-G.J.:
Section of Osteimmunology and Oral Immunology, Laboratory of Dental Reseach. FES Iztacala, National Autonomous University of Mexico (UNAM), Mexico State, Mexico
Lilia G.-H.A.:
Section of Osteimmunology and Oral Immunology, Laboratory of Dental Reseach. FES Iztacala, National Autonomous University of Mexico (UNAM), Mexico State, Mexico
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