title: Prediabetic changes in gene expression induced by aspartame and monosodium glutamate in Trans fat-fed C57Bl/6 J mice.
abstract: BACKGROUND
  The human diet has altered markedly during the past four decades, with the introduction of Trans hydrogenated fat, which extended the shelf-life of dietary oils and promoted a dramatic increase in elaidic acid (Trans-18.1) consumption. Food additives such as monosodium glutamate (MSG) and aspartame (ASP) were introduced to increase food palatability and reduce caloric intake. Nutrigenomics studies in small-animal models are an established platform for analyzing the interactions between various macro- and micronutrients. We therefore investigated the effects of changes in hepatic and adipose tissue gene expression induced by the food additives ASP, MSG or a combination of both additives in C57Bl/6 J mice fed a Trans fat-enriched diet.
  
  
  METHODS
  Hepatic and adipose tissue gene expression profiles, together with body characteristics, glucose parameters, serum hormone and lipid profiles were examined in C57Bl/6 J mice consuming one of the following four dietary regimens, commencing in utero via the mother's diet: [A] Trans fat (TFA) diet; [B] MSG + TFA diet; [C] ASP + TFA diet; [D] ASP + MSG + TFA diet.
  
  
  RESULTS
  Whilst dietary MSG significantly increased hepatic triglyceride and serum leptin levels in TFA-fed mice, the combination of ASP + MSG promoted the highest increase in visceral adipose tissue deposition, serum free fatty acids, fasting blood glucose, HOMA-IR, total cholesterol and TNFα levels. Microarray analysis of significant differentially expressed genes (DEGs) showed a reduction in hepatic and adipose tissue PPARGC1a expression concomitant with changes in PPARGC1a-related functional networks including PPARα, δ and γ. We identified 73 DEGs common to both adipose and liver which were upregulated by ASP + MSG in Trans fat-fed mice; and an additional 51 common DEGs which were downregulated.
  
  
  CONCLUSIONS
  The combination of ASP and MSG may significantly alter adiposity, glucose homeostasis, hepatic and adipose tissue gene expression in TFA-fed C57Bl/6 J mice.
authors.affiliation: Diabetes Research Unit, Department Cell Biology, King Faisal Specialist Hospital & Research Centre, PO BOX 3354, Riyadh 11211, Saudi Arabia.
authors.forename: Kate S
authors.initials: KS
authors.lastname: Collison
authors.affiliation: Diabetes Research Unit, Department Cell Biology, King Faisal Specialist Hospital & Research Centre, PO BOX 3354, Riyadh 11211, Saudi Arabia.
authors.forename: Nadine J
authors.initials: NJ
authors.lastname: Makhoul
authors.affiliation: Diabetes Research Unit, Department Cell Biology, King Faisal Specialist Hospital & Research Centre, PO BOX 3354, Riyadh 11211, Saudi Arabia.
authors.forename: Marya Z
authors.initials: MZ
authors.lastname: Zaidi
authors.affiliation: Diabetes Research Unit, Department Cell Biology, King Faisal Specialist Hospital & Research Centre, PO BOX 3354, Riyadh 11211, Saudi Arabia.
authors.forename: Angela
authors.initials: A
authors.lastname: Inglis
authors.affiliation: Diabetes Research Unit, Department Cell Biology, King Faisal Specialist Hospital & Research Centre, PO BOX 3354, Riyadh 11211, Saudi Arabia.
authors.forename: Bernard L
authors.initials: BL
authors.lastname: Andres
authors.affiliation: Diabetes Research Unit, Department Cell Biology, King Faisal Specialist Hospital & Research Centre, PO BOX 3354, Riyadh 11211, Saudi Arabia.
authors.forename: Rosario
authors.initials: R
authors.lastname: Ubungen
authors.affiliation: Diabetes Research Unit, Department Cell Biology, King Faisal Specialist Hospital & Research Centre, PO BOX 3354, Riyadh 11211, Saudi Arabia.
authors.forename: Soad
authors.initials: S
authors.lastname: Saleh
authors.affiliation: Diabetes Research Unit, Department Cell Biology, King Faisal Specialist Hospital & Research Centre, PO BOX 3354, Riyadh 11211, Saudi Arabia ; College of Medicine, Al-Faisal University, Riyadh, Saudi Arabia.
authors.forename: Futwan A
authors.initials: FA
authors.lastname: Al-Mohanna
keywords: Adipose; Aspartame; Gene expression; Liver; Metabolic dysregulation; Monosodium glutamate; Nutrigenomics; Trans-hydrogenated fat