Abstract
Background: High-fructose and/or low-mineral diets are relevant in metabolic syndrome (MS) development. Insulin resistance (IR) represents a central mechanism in MS development. Glucocorticoid signalling dysfunction and endoplasmic reticulum (ER) and oxidative stresses strongly contribute to IR and associate with MS. We have described that natural mineral-rich water ingestion delays fructose-induced MS development, modulates fructose effects on the redox state and glucocorticoid signalling and increases sirtuin 1 expression. Here, we investigated mineral-rich water ingestion effects on insulin signalling and ER homeostasis of fructose-fed rats.
Materials and methods: Adult male Sprague-Dawley rats had free access to standard-chow diet and different drinking solutions (8 weeks): tap water (CONT), 10%-fructose/tap water (FRUCT) or 10%-fructose/mineral-rich water (FRUCTMIN). Hepatic and adipose (visceral, VAT) insulin signalling and hepatic ER homeostasis (Western blot or PCR) as well as hepatic lipid accumulation were evaluated.
Results: Hepatic p-IRS1Ser307/IRS1 (tendency), p-IRS1Ser307, total JNK and (activated IRE1α)/(activated JNK) decreased with fructose ingestion, while p-JNK tended to increase; mineral-rich water ingestion, totally or partially, reverted all these effects. Total PERK, p-eIF2α (tendency) and total IRS1 (tendency) decreased in both fructose-fed groups. p-ERK/ERK and total IRE1α increasing tendencies in FRUCT became significant in FRUCTMIN (similar pattern for lipid area). Additionally, unspliced-XBP1 increased with mineral-rich water. In VAT, total ERK fructose-induced increase was partially prevented in FRUCTMIN.
Conclusions: Mineral-rich water modulation of fructose-induced effects on insulin signalling and ER homeostasis matches the better metabolic profile previously reported. Increased p-ERK/ERK, adding to decreased IRE1α activation, and increased unspliced-XBP1 and lipid area may protect against oxidative stress and IR development in FRUCTMIN.
Acknowledgments
We thank Unicer Bebidas, S.A., Portugal, for kindly providing Pedras Salgadas®, the hypersaline sodium-rich naturally sparkling mineral water used in this study. This work was supported by FCT (Fundação para a Ciência e Tecnologia, PEst-OE/SAU/UI0038/2014) through the Centro de Farmacologia e Biopatologia Química (U38/FCT), Faculty of Medicine, University of Porto, which integrated (until 31 December 2014) the Department of Biochemistry, Faculty of Medicine, University of Porto. Additional funding was provided by FCT (SFRH/BDE/33798/2009 and PTDC/DES/113580/2009) and by Unicer Bebidas, S.A., Portugal. We thank Sónia Norberto (from the Faculty of Medicine, Department of Biochemistry, University of Porto, Porto, Portugal) for the help with the micrographs of hepatic tissue stained with Oil Red O.
Competing interests: When considering the partial funding by Unicer Bebidas, S.A., it should be mentioned that the study here presented was developed, in its full extent, both in scientific terms and research equipment conditions, independently of the beverage company.
Author’s contribution: CDP performed western blot and PCR analysis, discussed and interpreted data and wrote the manuscript. EP performed PCR analysis. MS contributed to statistical analysis. IV and WX performed the hepatic histological evaluation; FC and PG revised critically the manuscript; RM and MJM designed and coordinated the study, discussed and interpreted data and wrote the manuscript. All authors read and approved the final manuscript.
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