Food additives with aldehyde skeleton exhibited leptin resistance in cells.

Obesity, a major health issue linked to metabolic disorders, is driven by multiple factors, including impaired leptin signaling, particularly in the Janus kinase 2 (JAK2)/Signal transducer and activator of transcription 3 (STAT3) pathway. This study investigated the impact of aldehyde-containing food additives on leptin receptor activated signaling in cells. We examined the effects of 39 different aldehyde-containing compounds, commonly used in food additives, on leptin-induced STAT3 transcriptional activity through a reporter gene assay. Three aldehydes, i.e., 2-pyrrolecarboxaldehyde, o-anisaldehyde, and piperonal were found to reduce leptin-induced STAT3 transcriptional activity in a concentration-dependent manner without affecting cell viability. These additives did not alter conformational changes of the leptin receptor, STAT3 phosphorylation, or its nuclear translocation, nor did they induce endoplasmic reticulum stress. These additives likely affect a downstream step in leptin signaling, specifically transcriptional regulation by STAT3, without disrupting early receptor signaling events. These finding suggest that some aldehyde-based food additives may contribute to leptin resistance and potentially to the development of obesity.