Fetal Programming of the Endocrine Pancreas: Impact of a Maternal Low-Protein Diet on Gene Expression in the Perinatal Rat Pancreas.
Study Goal
The researchers aimed to characterize the perinatal rat pancreas transcriptome and identify regulatory pathways affected by a low-protein diet (LP) compared to a control diet (CO).
Results Summary
The LP diet induced changes in transcripts related to RNA transcription, gene regulation, cell migration, and apoptosis, while downregulating genes like Neurog3, Etv5, and Gas6. The CO group showed enrichment in metabolic pathways related to sterol and lipid metabolism.
Population
Perinatal rats (embryonic day 20 and postnatal days 0 and 2).
Effective Dosage
Not specified
Duration
From embryonic day 20 to postnatal day 2.
Interactions
None mentioned
| Intervention | Direction | Endpoint | Population | Dosage | Impact | Claim # |
|---|---|---|---|---|---|---|
regular control diet (CO) | increase | pancreas metabolic pathways related to sterol and lipid metabolism | offspring of mothers fed a regular control diet | - | highly enriched | #1 |
low-protein diet (LP) | increase | transcripts involved in RNA transcription and gene regulation, as well as cell migration and apoptosis | offspring of mothers fed a low-protein diet | - | induced changes | #2 |
regular control diet (CO) | increase | growth arrest specific 6 (Gas6), legumain (Lgmn), Ets variant gene 5 (Etv5), alpha-fetoprotein (Afp), dual-specificity phosphatase 6 (Dusp6), and angiopoietin-like 4 (Angptl4) | offspring of mothers fed a regular control diet | - | markedly upregulated | #3 |
low-protein diet (LP) | decrease | neurogenin 3 (Neurog3), Etv5, Gas6, Dusp6, signaling transducer and activator of transcription 3 (Stat3), growth hormone receptor (Ghr), prolactin receptor (Prlr), and Gas6 receptor (AXL receptor tyrosine kinase; Axl) | offspring of mothers fed a low-protein diet | - | induced the downregulation | #4 |
low-protein diet (LP) | increase | transcripts related to inflammatory responses and cell motility | offspring of mothers fed a low-protein diet | - | upregulated | #5 |
low-protein diet (LP) | increase | exocrine and endocrine in the pancreas | offspring of mothers fed a low-protein diet | - | marked adaptations | #6 |
In rats, the time of birth is characterized by a transient rise in beta cell replication, as well as beta cell neogenesis and the functional maturation of the endocrine pancreas. However, the knowledge of the gene expression during this period of beta cell expansion is incomplete. The aim was to characterize the perinatal rat pancreas transcriptome and to identify regulatory pathways differentially regulated at the whole organ level in the offspring of mothers fed a regular control diet (CO) and of mothers fed a low-protein diet (LP). We performed mRNA expression profiling via the microarray analysis of total rat pancreas samples at embryonic day (E) 20 and postnatal days (P) 0 and 2. In the CO group, pancreas metabolic pathways related to sterol and lipid metabolism were highly enriched, whereas the LP diet induced changes in transcripts involved in RNA transcription and gene regulation, as well as cell migration and apoptosis. Moreover, a number of individual transcripts were markedly upregulated at P0 in the CO pancreas: growth arrest specific 6 (Gas6), legumain (Lgmn), Ets variant gene 5 (Etv5), alpha-fetoprotein (Afp), dual-specificity phosphatase 6 (Dusp6), and angiopoietin-like 4 (Angptl4). The LP diet induced the downregulation of a large number of transcripts, including neurogenin 3 (Neurog3), Etv5, Gas6, Dusp6, signaling transducer and activator of transcription 3 (Stat3), growth hormone receptor (Ghr), prolactin receptor (Prlr), and Gas6 receptor (AXL receptor tyrosine kinase; Axl), whereas upregulated transcripts were related to inflammatory responses and cell motility. We identified differentially regulated genes and transcriptional networks in the perinatal pancreas. These data revealed marked adaptations of exocrine and endocrine in the pancreas to the low-protein diet, and the data can contribute to identifying novel regulators of beta cell mass expansion and functional maturation and may provide a valuable tool in the generation of fully functional beta cells from stem cells to be used in replacement therapy.