title: Sex-dimorphism in cardiac nutrigenomics: effect of trans fat and/or monosodium glutamate consumption.
abstract: BACKGROUND
  A paucity of information on biological sex-specific differences in cardiac gene expression in response to diet has prompted this present nutrigenomics investigation. Sexual dimorphism exists in the physiological and transcriptional response to diet, particularly in response to high-fat feeding. Consumption of Trans-fatty acids (TFA) has been linked to substantially increased risk of heart disease, in which sexual dimorphism is apparent, with males suffering a higher disease rate. Impairment of the cardiovascular system has been noted in animals exposed to Monosodium Glutamate (MSG) during the neonatal period, and sexual dimorphism in the growth axis of MSG-treated animals has previously been noted. Processed foods may contain both TFA and MSG.
  
  
  METHODS
  We examined physiological differences and changes in gene expression in response to TFA and/or MSG consumption compared to a control diet, in male and female C57BL/6J mice.
  
  
  RESULTS
  Heart and % body weight increases were greater in TFA-fed mice, who also exhibited dyslipidemia (P < 0.05). Hearts from MSG-fed females weighed less than males (P < 0.05). 2-factor ANOVA indicated that the TFA diet induced over twice as many cardiac differentially expressed genes (DEGs) in males compared to females (P < 0.001); and 4 times as many male DEGs were downregulated including Gata4, Mef2d and Srebf2. Enrichment of functional Gene Ontology (GO) categories were related to transcription, phosphorylation and anatomic structure (P < 0.01). A number of genes were upregulated in males and downregulated in females, including pro-apoptotic histone deacetylase-2 (HDAC2). Sexual dimorphism was also observed in cardiac transcription from MSG-fed animals, with both sexes upregulating approximately 100 DEGs exhibiting sex-specific differences in GO categories. A comparison of cardiac gene expression between all diet combinations together identified a subset of 111 DEGs significant only in males, 64 DEGs significant in females only, and 74 transcripts identified as differentially expressed in response to dietary manipulation in both sexes.
  
  
  CONCLUSIONS
  Our model identified major changes in the cardiac transcriptional profile of TFA and/or MSG-fed mice compared to controls, which was reflected by significant differences in the physiological profile within the 4 diet groups. Identification of sexual dimorphism in cardiac transcription may provide the basis for sex-specific medicine in the future.
authors.affiliation: Cell Biology & Diabetes Research Unit, Department of Biological & Medical Research, King Faisal Specialist Hospital & Research Centre, PO BOX 3354, Riyadh 11211, Saudi Arabia. kate@kfshrc.edu.sa
authors.forename: Kate S
authors.initials: KS
authors.lastname: Collison
authors.forename: Marya Z
authors.initials: MZ
authors.lastname: Zaidi
authors.forename: Zakia
authors.initials: Z
authors.lastname: Maqbool
authors.forename: Soad M
authors.initials: SM
authors.lastname: Saleh
authors.forename: Angela
authors.initials: A
authors.lastname: Inglis
authors.forename: Nadine J
authors.initials: NJ
authors.lastname: Makhoul
authors.forename: Razan
authors.initials: R
authors.lastname: Bakheet
authors.forename: Mohammed
authors.initials: M
authors.lastname: Shoukri
authors.forename: Futwan A
authors.initials: FA
authors.lastname: Al-Mohanna
mesh_terms: D000818:Animals; D001835:Body Weight; D004041:Dietary Fats / Q000009:adverse effects*; D005260:Female; D005786:Gene Expression Regulation; D006321:Heart / Q000503:physiopathology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D054647:Nutrigenomics; D020411:Oligonucleotide Array Sequence Analysis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012727:Sex Characteristics; D012970:Sodium Glutamate / Q000009:adverse effects*; D044242:Trans Fatty Acids / Q000009:adverse effects*; D059467:Transcriptome
chemical_list: D004041:Dietary Fats; D044242:Trans Fatty Acids; D012970:Sodium Glutamate
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