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Published on: February 3, 2017
A single high-fat meal alters human soluble RAGE profiles and PBMC RAGE expression with no effect of prior aerobic
Kelly N Z Fuller1, Rudy J Valentine2, Edwin R Miranda1,3
1Department of Kinesiology and Nutrition, University of Illinois at Chicago, Chicago, Illinois.
Abstract:
A high-fat diet can induce inflammation and metabolic diseases such as diabetes and atherosclerosis. The receptor for advanced glycation endproducts (RAGE) plays a critical role in metabolic disease pathophysiology and the soluble form of the receptor (sRAGE) can mitigate these effects. However, little is known about RAGE in the postprandial condition and the effect of exercise in this context. Thus, we aimed to determine the effects of a single high-fat meal (HFM) with and without prior exercise on peripheral blood mononuclear cell (PBMC) RAGE biology. Healthy males (n = 12) consumed a HFM on two occasions, one without prior exercise and one 16-18 hours following acute aerobic exercise. Total soluble RAGE (sRAGE) and endogenous secretory RAGE (esRAGE) were determined via ELISA and cleaved RAGE (cRAGE) was calculated as the difference between the two. Isolated PBMCs were analyzed for RAGE, ADAM10, TLR4, and MyD88 protein expression and ADAM10 activity. The HFM significantly (P < 0.01) attenuated sRAGE, esRAGE, and cRAGE by 9.7%, 6.9%, and 10.5%, respectively. Whereas, the HFM increased PBMC RAGE protein expression by 10.3% (P < 0.01), there was no meal effect on PBMC TLR4, MYD88, or ADAM10 protein expression, nor ADAM10 activity. There was also no exercise effect on any experimental outcomes. These findings suggest that PBMC RAGE and soluble RAGE may be important in the postprandial response to a HFM, and that prior aerobic exercise does not alter these processes in young healthy adult males. The mechanisms by which a HFM induces RAGE expression and reduces circulating soluble RAGE isoforms requires further study.
Insights
A high-fat meal reduced soluble receptor for advanced glycation endproducts (sRAGE) and increased its expression on cells, but prior exercise had no effect on these metabolic changes.
Area of Science:
- Metabolic Health
- Inflammation Research
- Exercise Physiology
Background:
- High-fat diets (HFDs) trigger inflammation and metabolic diseases like diabetes and atherosclerosis.
- The receptor for advanced glycation endproducts (RAGE) is crucial in metabolic disease; its soluble form (sRAGE) offers protection.
- The role of RAGE in the postprandial state and the influence of exercise remain unclear.
Purpose of the Study:
- To investigate the impact of a single high-fat meal (HFM) on peripheral blood mononuclear cell (PBMC) RAGE biology.
- To determine if acute aerobic exercise modifies the postprandial response to an HFM concerning RAGE.
- To analyze changes in soluble RAGE isoforms (sRAGE, esRAGE, cRAGE) and PBMC RAGE, ADAM10, TLR4, and MyD88 expression.
Main Methods:
- Twelve healthy males consumed an HFM on two separate occasions.
- One HFM was preceded by acute aerobic exercise (16-18 hours prior); the other was not.
- Blood samples were analyzed for sRAGE, esRAGE, and PBMC expression of RAGE, ADAM10, TLR4, and MyD88.
Main Results:
- The HFM significantly decreased circulating sRAGE, esRAGE, and calculated cleaved RAGE (cRAGE) levels.
- Conversely, the HFM significantly increased RAGE protein expression on PBMCs.
- No significant effects of the HFM or prior exercise were observed on PBMC TLR4, MyD88, or ADAM10 expression or activity.
Conclusions:
- PBMC RAGE and soluble RAGE isoforms are involved in the postprandial response to HFM in healthy males.
- Acute aerobic exercise did not alter the observed changes in PBMC RAGE biology or circulating sRAGE after an HFM.
- Further research is needed to elucidate the mechanisms behind HFM-induced RAGE changes and reduced soluble RAGE.
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