Assessment of EN-RAGE, sRAGE, and its isoforms: cRAGE, esRAGE in obese patients treated by moderate caloric restriction combined with physical activity conducted in hospital condition

• Published in: Cytokine (Philadelphia, Pa.) Vol. 180; p. 156665
• Main Authors: Kanikowska, Dominika, Kanikowska, Alina, Strojny, Zofia, Kawka, Edyta, Zawada, Agnieszka, Rutkowski, Rafał, Litwinowicz, Monika, Sato, Maki, Grzymisławski, Marian, Bręborowicz, Andrzej, Witowski, Janusz, Korybalska, Katarzyna
• Format: Journal Article
• Language: English
• Published: England Elsevier Ltd 01.08.2024
• Subjects: Adult; Antigens, Neoplasm; Body Mass Index; Caloric Restriction - methods; cRAGE; EN-RAGE; esRAGE; Exercise - physiology; Female; Humans; Male; Middle Aged; Mitogen-Activated Protein Kinases; Moderate calorie restriction; Motor Activity - physiology; Obesity; Obesity - blood; Obesity - diet therapy; Obesity - therapy; Protein Isoforms - blood; Receptor for Advanced Glycation End Products - blood; Receptors, Immunologic - blood; sRAGE; Obesity; cRAGE; EN-RAGE; sRAGE; Moderate calorie restriction; esRAGE
• ISSN: 1043-4666; 1096-0023; 1096-0023
• DOI: 10.1016/j.cyto.2024.156665

•sRAGE and its isoforms cleaved − cRAGE and secretory-esRAGE are low in obese patients and are not modified by moderate caloric restriction.•Proinflammatory EN-RAGE, an endogenous receptor ligand for AGE, elevated in obese subjects, is modified by moderate caloric restriction.•EN-RAGE instead of RAGE isoforms could help indicate a better outcome of moderate. AGEs, their receptor (RAGE), and the extracellular newly identified receptor for AGEs product-binding protein (EN-RAGE) are implicated in the pathogenesis of inflammation. We analyzed serum EN-RAGE, soluble RAGE (sRAGE), and their isoforms: endogenous secretory − esRAGE and cleaved − cRAGE concentrations in lean controls (n = 74) and in patients with obesity (n = 71) treated for three weeks with moderate calorie restriction (CR) combined with physical activity in a hospital condition. Using the ELISA method, serum sRAGE, esRAGE, and EN-RAGE were measured before and after CR. The serum level of sRAGE and esRAGE in patients with obesity was lower than that in non-obese individuals, contrary to cRAGE. EN-RAGE concentration was about three times higher in obese patients. Gradually, a rise in BMI resulted in sRAGE, esRAGE reduction, and EN-RAGE increase. The sRAGE concentration was sex-dependent, indicating a higher value in lean men. A moderate negative correlation was observed between BMI and all RAGE isoforms, whereas EN-RAGE displays a positive correlation. CR resulted in an expected decrease in anthropometric, metabolic, and proinflammatory parameters and EN-RAGE, but no RAGE isoforms. The ratio EN-RAGE/sRAGE was higher in obese humans than in control and was not modified by CR. Obesity decreases sRAGE and esRAGE and increases EN-RAGE concentration. Moderate CR and physical activity by decreasing inflammation reduces EN-RAGE but is insufficient to increase sRAGE and esRAGE to the extent observed in lean patients. EN-RAGE instead of sRAGE could be helpful to indicate a better outcome of moderate dietary intervention in obese subjects.