Endogenous secretory RAGE increases with improvements in body composition and is associated with markers of adipocyte health

• DOI: 10.1016/j.numecd.2018.07.009
• Publication Date: 2018-08-02T10:38:05Z
• Authors: E.R. Miranda; K.N.Z. Fuller; R.K. Perkins; C.M. Kroeger; J.F. Trepanowski; K.A. Varady; J.M. Haus
• Keywords: Adult; Chicago; Male; 2. Zero hunger; 0303 health sciences; Time Factors; Receptor for Advanced Glycation End Products; Enzyme-Linked Immunosorbent Assay; Fasting; Intra-Abdominal Fat; Middle Aged; Magnetic Resonance Imaging; Subcutaneous Fat, Abdominal; 03 medical and health sciences; Absorptiometry, Photon; Treatment Outcome; Adipocytes; Humans; Female; Obesity; Energy Intake; Biomarkers; Adiposity

The receptor for advanced glycation end products (RAGE) is implicated in obesogenesis. Conversely, soluble RAGE (sRAGE) competitively inhibits RAGE. Our aim was to determine the effects of weight-loss via alternate day fasting (ADF) on sRAGE isoforms and evaluate potential relationships with body composition.42 obese participants were randomized to control (CON) or ADF. For 24 weeks, the ADF group consumed 25% or 125% of their caloric requirements on alternating days while the CON group did not change their diet. Body fat was measured via DXA, visceral fat (VAT) via MRI and subcutaneous fat (SAT) was derived by subtracting VAT from total fat. sRAGE isoforms were measured via ELISAs. After 24 weeks, ADF -6.8 (-9.5, -3.5)kg (Median, IQR) lost more weight than CON -0.3 (-1.9, 1.0)kg (p < 0.05). The change in endogenous secretory RAGE (esRAGE) was different between ADF 15 (-30, 78)pg/mL and CON -21 (-72, 16)pg/mL after 24 weeks (p < 0.05). To examine the effect of changes in body composition, the cohort was stratified by median weight-, fat-, SAT-, and VAT-loss. The changes in all sRAGE isoforms were different between those above and below median weight-loss (p < 0.05) with sRAGE isoforms tending to decrease in individuals below the median. Changes in total sRAGE and esRAGE were different between individuals above compared to below median fat- and SAT-loss (p < 0.05). Those above median fat-loss increased esRAGE by 29 (-5, 66)pg/mL (p < 0.05).Improvements in body composition are related to increased sRAGE isoforms, implicating sRAGE as a potential target for the treatment of obesity.NCT00960505.