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

BACKGROUND AND AIMS: 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. METHODS AND RESULTS: 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). CONCLUSION: Improvements in body composition are related to increased sRAGE isoforms, implicating sRAGE as a potential target for the treatment of obesity. CLINICAL TRIAL REGISTRATION: NCT00960505.

Benefit of a low-fat over high-fat diet on vascular health during alternate day fasting.

BACKGROUND: Alternate day fasting (ADF) with a low-fat (LF) diet improves brachial artery flow-mediated dilation (FMD). Whether these beneficial effects can be reproduced with a high-fat (HF) diet remains unclear. OBJECTIVE: This study compared the effects of ADF-HF to ADF-LF regimens on FMD. The role that adipokines have in mediating this effect was also investigated. METHODS: Thirty-two obese subjects were randomized to an ADF-HF (45% fat) or ADF-LF diet (25% fat), consisting of two phases: (1) a 2-week baseline weight maintenance period and (2) an 8-week ADF weight loss period. Food was provided throughout the study. RESULTS: Body weight was reduced (P<0.0001) in the ADF-HF (4.4±1.0 kg) and ADF-LF group (3.7±0.7 kg). FMD decreased (P<0.05) by ADF-HF relative to baseline (7±1 to 5±2%) and increased (P<0.05) by ADF-LF (5±1 to 7±2%). Blood pressure remained unchanged in both groups. Adiponectin increased (P<0.05) in the ADF-HF (43±7%) and ADF-LF group (51±7%). Leptin and resistin decreased (P<0.05) in the ADF-HF (32±5%; 23±5%) and ADF-LF group (30±3%; 27±4%). Increases in adiponectin were associated with augmented FMD in the ADF-LF group only (r=0.34, P=0.03). CONCLUSION: Thus, improvements in FMD with ADF may only occur with LF diets and not with HF diets, and adipokines may not have a significant role in mediating this effect.

Alternate day fasting increases LDL particle size independently of dietary fat content in obese humans.

Alternate day fasting (ADF) with a low-fat (LF) diet increases low-density lipoprotein (LDL) particle size. Whether these beneficial effects can be reproduced by a high-fat (HF) ADF diet is unclear. This study compared an ADF-HF to an ADF-LF diet on plasma lipids, LDL size and high-density lipoprotein (HDL) size. Thirty-five obese subjects were randomized to an ADF-HF or ADF-LF diet for 10 weeks. Body weight decreased (P<0.0001) by 4.3±1.0 kg (4.8±1.1%) and 3.7±0.7 kg (4.2±0.8%) in the ADF-HF and ADF-LF group, respectively. LDL cholesterol was reduced (P<0.0001) by 19±8 mg/dl (18±5%) by ADF-HF and 28±7 mg/dl (25±3%) by ADF-LF. LDL particle size increased (P<0.005) by 3±1 Å in both groups. The proportion of small LDL particles decreased (P<0.005) by 8±2% and 11±3% in the ADF-HF and ADF-LF groups, respectively. HDL cholesterol and HDL size remained unchanged. Thus, our results suggest that the ADF-HF diet is equally as effective as the ADF-LF diet in improving LDL particle size and distribution.