Abstract
Nutrigenomic evidence supports the idea that Type 2 Diabetes Mellitus (T2DM) arises due to the interactions between the transcriptome, individual genetic profiles, lifestyle, and diet. Since eggs are a nutrient dense food containing bioactive ingredients that modify gene expression, our goal was to examine the role of whole egg consumption on the transcriptome during T2DM. We analyzed whether whole egg consumption in Zucker Diabetic Fatty (ZDF) rats alters microRNA and mRNA expression across the adipose, liver, kidney, and prefrontal cortex tissue. Male ZDF (fa/fa) rats (n = 12) and their lean controls (fa/+) (n = 12) were obtained at 6 wk of age. Rats had ad libitum access to water and were randomly assigned to a modified semi-purified AIN93G casein-based diet or a whole egg-based diet, both providing 20% protein (w/w). TotalRNA libraries were prepared using QuantSeq 3' mRNA-Seq and Lexogen smallRNA library prep kits and were further sequenced on an Illumina HighSeq3000. Differential gene expression was conducted using DESeq2 in R and Benjamini-Hochberg adjusted P-values controlling for false discovery rate at 5%. We identified 9 microRNAs and 583 genes that were differentially expressed in response to 8 wk of consuming whole egg-based diets. Kyto Encyclopedia of Genes and Genomes/Gene ontology pathway analyses demonstrated that 12 genes in the glutathione metabolism pathway were upregulated in the liver and kidney of ZDF rats fed whole egg. Whole egg consumption primarily altered glutathione pathways such as conjugation, methylation, glucuronidation, and detoxification of reactive oxygen species. These pathways are often negatively affected during T2DM, therefore this data provides unique insight into the nutrigenomic response of dietary whole egg consumption during the progression of T2DM.
Highlights
Type 2 Diabetes Mellitus (T2DM) is an insulin independent metabolic disease characterized by chronic hyperglycemia and concomitant insulin resistance and it is estimated that greater than 415 million adults worldwide have T2DM [1]
Differential gene expression of Zucker Diabetic Fatty rats fed whole egg several groups have suggested that WE provide antioxidant properties [13, 25], either through antioxidant peptides in the egg yolk [11] or other reactive oxygen species-reducing nutrients [26]
Other studies examining the role of quail egg consumption in rat models of T2DM have demonstrated upregulation of glutathione metabolism in alloxan-induced T2DM in Wistar rats [25] and improved oxidative stress profiles in streptozotocin-injected rats [27]
Summary
Type 2 Diabetes Mellitus (T2DM) is an insulin independent metabolic disease characterized by chronic hyperglycemia and concomitant insulin resistance and it is estimated that greater than 415 million adults worldwide have T2DM [1]. Sekhar and colleagues examined the ability of patients with uncontrolled and controlled T2DM to synthesize glutathione via measuring isotopically labelled glycine [4]. They reported that patients with uncontrolled T2DM were severely deficient in the ability to maintain glutathione metabolism in cardiac tissue [5], which may be, in part, due to hyperglycemia decreasing L-cysteine concentrations [6] and the reduced flux of methionine to cysteine [7]. The Zucker Diabetic Fatty (ZDF) rat model of T2DM displays increased oxidative stress [8], whereby endogenous protective antioxidants like glutathione are downregulated in ZDF rats [9]. The gene expression profiles in animal models of T2DM, such as the ZDF rat, is consistent with gene expression profiles of humans with T2DM [8], making this a suitable model to explore the global gene expression effects of diet in the ZDF rat
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