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In vitro effect of various food additives and plant extracts on the progression of MASLD.

Rafael RÍOS BERNABÉ, Natalia LATES PROFIR, Rafael RÍOS DE MOYA-ANGELER, Carmen FRONTELA SASandA, Alfonso RÍOS BERNABÉ and Rubén LÓPEZ NICOLÁS

Sustained exposure to dietary patterns with a high content of ultra-processed foods has been linked to a significant increase in the risk of developing various metabolic disorders, including metabolic dysfunction-associated steatotic liver disease (MASLD). The growing global prevalence of MASLD highlights the urgent need to elucidate its pathogenic mechanisms more precisely, since, due to the different pathways involved, there are currently no recognised effective therapies, reinforcing the strategic importance of identifying new molecular targets and specific therapeutic approaches. The HepG2 cell line is a relevant and effective in vitro model for studying hepatic steatosis. Some plant extracts have demonstrated hepatoprotective activity through the modulation of metabolic pathways that suppress lipid accumulation in the liver. However, the available knowledge on additives used in the formulation of ultra-processed foods (UPF) remains limited.The aim of this research was to analyse the effect of different food additives and plant extracts on the establishment and evolution of MASLD in HepG2 cells.The human liver cell line HepG2 was used as an in vitro model. The different food compounds were evaluated at a concentration of 1% for 48 hours in EMEM medium. After 24 hours of exposure, palmitic acid was added at a concentration of 200 mM to induce steatosis. Subsequently, Oil Red O staining was performed to quantify intracellular lipid accumulation.The results indicated that cells exposed to plant extracts (curcumin, hesperidin, and lycopene) showed minimal intracellular lipid accumulation. In contrast, treatment with the food additive tartrazine was associated with a marked increase in the size of cytoplasmic lipid droplets.The different behaviour between plant extracts and tartrazine suggests that these compounds act through opposing cellular mechanisms in the regulation of lipid content. This raises the need to investigate further how certain food additives could contribute to metabolic imbalances in the liver.Plant extracts could exert a beneficial modulatory effect by attenuating the processes that lead to the induction of hepatocellular steatosis. Conversely, various food additives show signs of promoting intracellular lipid accumulation, thus favouring the onset of steatosis compatible with the early stages of MASLD.