Possible role of food additives on formation of leptin resistance in obesity

Abstract

Obesity is known to be triggered by various factors and is a recognized as a risk factor for metabolic diseases. Leptin is an anti-obesity hormone, which can inhibit food intake and increase energy expenditure. It is suggested that leptin resistance is one of the underlying mechanisms of obesity. Our research group is studying the impact of endoplasmic reticulum (ER) stress on development of leptin resistance. We previously found that 4-hydroxynonenal, which contains aldehyde, induced ER stress and inhibited leptin-induced STAT3 phosphorylation. In the present study, we identified several food additives, which contains aldehydes that could potentially cause leptin resistance through screening using STAT3 luciferase assay at neuronal cells expressing Ob-Rb leptin receptor. We also evaluated the downstream of leptin signal by analyzing STAT3 signal by Western blotting. We found that the several food additive can inhibit leptin-induced STAT3 signal. We are now analyzing the effect of food additives on ObR leptin receptor function by BRET technique. Overall, our results suggests that some food additives, which contain aldehydes, may potentially lead to obesity through formation of leptin resistance.