title: Ingestion of a natural mineral-rich water in an animal model of metabolic syndrome: effects in insulin signalling and endoplasmic reticulum stress.
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.
  
  
  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.
authors.forename: Cidália D
authors.initials: CD
authors.lastname: Pereira
authors.forename: Emanuel
authors.initials: E
authors.lastname: Passos
authors.forename: Milton
authors.initials: M
authors.lastname: Severo
authors.forename: Isabel
authors.initials: I
authors.lastname: Vitó
authors.forename: Xiaogang
authors.initials: X
authors.lastname: Wen
authors.forename: Fátima
authors.initials: F
authors.lastname: Carneiro
authors.forename: Pedro
authors.initials: P
authors.lastname: Gomes
authors.forename: Rosário
authors.initials: R
authors.lastname: Monteiro
authors.forename: Maria J
authors.identifier: http://orcid.org/0000-0002-3560-3261
authors.initials: MJ
authors.lastname: Martins
mesh_terms: D000273:Adipose Tissue / Q000378:metabolism; D000818:Animals; D004032:Diet; D060766:Drinking Water / Q000737:chemistry*; D059865:Endoplasmic Reticulum Stress; D005938:Glucocorticoids / Q000378:metabolism; D007328:Insulin / Q000378:metabolism*; D050356:Lipid Metabolism; D008099:Liver / Q000378:metabolism; D008297:Male; D024821:Metabolic Syndrome / Q000378:metabolism; D008900:Mineral Waters; D018384:Oxidative Stress; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction
chemical_list: D060766:Drinking Water; D005938:Glucocorticoids; D007328:Insulin; D008900:Mineral Waters