Changes in Appetite Regulation-Related Signaling Pathways in the Brain of Mice Supplemented with Non-nutritive Sweetener
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Changes in Appetite Regulation‑Related Signaling Pathways in the Brain of Mice Supplemented with Non‑nutritive Sweeteners Gerson G Contreras‑Chavez1 · José A Estrada1 · Irazú Contreras1 Received: 19 August 2020 / Accepted: 19 October 2020 © Springer Science+Business Media, LLC, part of Springer Nature 2020
Abstract Non-nutritive sweeteners (NNSs) are commonly used to prevent weight gain and development of metabolic diseases associated with consumption of high-energy diets. Recent studies have demonstrated that these compounds may have unwanted detrimental effects under specific circumstances in vivo. In particular, an association between NNS consumption and changes in signaling pathways involved in the hunger-satiety system in the brain has been reported. Nonetheless, the extent of alterations in brain signaling pathways associated with consumption of these compounds has not been determined. The objective of this study was to determine the effect of frequent consumption of NNSs on the expression of proteins involved in signaling pathways related to appetite control in the brain in vivo. Eight-week-old BALB/c mice were supplemented with sucrose, sucralose, or steviol glycosides in their daily drinking water for 6 weeks. Subsequently, total brain protein extracts were used to analyze the expression of total and phosphorylated JAK2, STAT5, ERK 1/2, JNK, as well as SHP-2 and POMC, by western blot. Serum concentrations of leptin and α-MSH were quantified by ELISA. Results show that consumption of NNSs promotes significant changes in these signaling pathways, reducing the expression of pSTAT5/STAT5, pERK 1/2, SHP-2, and pJNK/JNK in male mice supplemented with steviol glycosides. Furthermore, consumption of steviol glycosides induced a decrease of α-MSH in male mice. In contrast, steviol glycosides induced overexpression of pSTAT5, pERK, and SHP-2 in females. These data suggest that chronic consumption of NNSs promotes sex-specific changes in signaling pathways related to the central hunger-satiety system in vivo. Keywords Sweeteners · Signaling pathways · Brain · Hunger-satiety system
Introduction Sweeteners are food additives that provide sweet taste. They are usually classified as nutritive and non-nutritive, according to the amount of energy they provide. Non-nutritive sweeteners (NNSs) provide sweetness, but not energy (Fitch and Keim 2012). Consumption of NNSs has been an increasingly common practice in the general population, in order to reduce dietary calorie intake. Sucralose and steviol glycosides are included among the most commonly used NNSs. They are often used in the food industry and have been well accepted by consumers as part of multiple commercial * Irazú Contreras [email protected] 1
Laboratorio de Neuroquímica, Facultad de Medicina, Universidad Autónoma del Estado de México, Paseo Tollocan S/N Esq. Jesús Carranza, Colonia Moderna de La Cruz, Estado de México 50180 Toluca, Mexico
products. In a recent study performed in four countries, it was observed that NNS are present in 5% of commerc
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