Intestinal gluconeogenesis is downregulated in pediatric patients with celiac disease
(2022) In BMC Medicine 20(1).- Abstract
Background: Untreated celiac disease (CD) patients have increased levels of blood glutamine and a lower duodenal expression of glutaminase (GLS). Intestinal gluconeogenesis (IGN) is a process through which glutamine is turned into glucose in the small intestine, for which GLS is crucial. Animal studies suggest impaired IGN may have long-term effects on metabolic control and be associated with the development of type 2 diabetes and non-alcoholic fatty liver disease (NAFLD). The aim of this study was to thoroughly investigate IGN at the gene expression level in children with untreated celiac disease. Methods: Quantitative polymerase chain reaction (qPCR) was used to quantify the expression of 11 target genes related to IGN using the... (More)
Background: Untreated celiac disease (CD) patients have increased levels of blood glutamine and a lower duodenal expression of glutaminase (GLS). Intestinal gluconeogenesis (IGN) is a process through which glutamine is turned into glucose in the small intestine, for which GLS is crucial. Animal studies suggest impaired IGN may have long-term effects on metabolic control and be associated with the development of type 2 diabetes and non-alcoholic fatty liver disease (NAFLD). The aim of this study was to thoroughly investigate IGN at the gene expression level in children with untreated celiac disease. Methods: Quantitative polymerase chain reaction (qPCR) was used to quantify the expression of 11 target genes related to IGN using the delta-delta Ct method with three reference genes (GUSB, IPO8, and YWHAZ) in duodenal biopsies collected from 84 children with untreated celiac disease and 58 disease controls. Results: Significantly lower expression of nine target genes involved in IGN was seen in duodenal biopsies from CD patients compared with controls: FBP1, G6PC, GLS, GPT1, PCK1, PPARGC1A, SLC2A2, SLC5A1, and SLC6A19. No significant difference in the expression was observed for G6PC3 or GOT1. Conclusions: Children with untreated celiac disease have lower expression of genes important for IGN. Further studies are warranted to disentangle whether this is a consequence of intestinal inflammation or due to an impaired metabolic pathway shared with other chronic metabolic diseases. Impaired IGN could be a mechanism behind the increased risk of NAFLD seen in CD patients.
(Less)
- author
- Karlson, Olof ; Arnell, Henrik ; Gudjonsdottir, Audur H. ; Agardh, Daniel LU and Torinsson Naluai, Åsa
- organization
- publishing date
- 2022-12
- type
- Contribution to journal
- publication status
- published
- subject
- keywords
- Celiac disease, Gluten, intestinal gluconeogenesis, Non-alcoholic fatty liver disease
- in
- BMC Medicine
- volume
- 20
- issue
- 1
- article number
- 440
- publisher
- BioMed Central (BMC)
- external identifiers
-
- scopus:85141654359
- pmid:36369023
- ISSN
- 1741-7015
- DOI
- 10.1186/s12916-022-02635-3
- language
- English
- LU publication?
- yes
- id
- 6d8edd5b-6eef-4b51-bf26-09254567ac94
- date added to LUP
- 2022-12-05 15:45:42
- date last changed
- 2024-04-04 13:43:42
@article{6d8edd5b-6eef-4b51-bf26-09254567ac94,
abstract = {{<p>Background: Untreated celiac disease (CD) patients have increased levels of blood glutamine and a lower duodenal expression of glutaminase (GLS). Intestinal gluconeogenesis (IGN) is a process through which glutamine is turned into glucose in the small intestine, for which GLS is crucial. Animal studies suggest impaired IGN may have long-term effects on metabolic control and be associated with the development of type 2 diabetes and non-alcoholic fatty liver disease (NAFLD). The aim of this study was to thoroughly investigate IGN at the gene expression level in children with untreated celiac disease. Methods: Quantitative polymerase chain reaction (qPCR) was used to quantify the expression of 11 target genes related to IGN using the delta-delta Ct method with three reference genes (GUSB, IPO8, and YWHAZ) in duodenal biopsies collected from 84 children with untreated celiac disease and 58 disease controls. Results: Significantly lower expression of nine target genes involved in IGN was seen in duodenal biopsies from CD patients compared with controls: FBP1, G6PC, GLS, GPT1, PCK1, PPARGC1A, SLC2A2, SLC5A1, and SLC6A19. No significant difference in the expression was observed for G6PC3 or GOT1. Conclusions: Children with untreated celiac disease have lower expression of genes important for IGN. Further studies are warranted to disentangle whether this is a consequence of intestinal inflammation or due to an impaired metabolic pathway shared with other chronic metabolic diseases. Impaired IGN could be a mechanism behind the increased risk of NAFLD seen in CD patients.</p>}},
author = {{Karlson, Olof and Arnell, Henrik and Gudjonsdottir, Audur H. and Agardh, Daniel and Torinsson Naluai, Åsa}},
issn = {{1741-7015}},
keywords = {{Celiac disease; Gluten; intestinal gluconeogenesis; Non-alcoholic fatty liver disease}},
language = {{eng}},
number = {{1}},
publisher = {{BioMed Central (BMC)}},
series = {{BMC Medicine}},
title = {{Intestinal gluconeogenesis is downregulated in pediatric patients with celiac disease}},
url = {{http://dx.doi.org/10.1186/s12916-022-02635-3}},
doi = {{10.1186/s12916-022-02635-3}},
volume = {{20}},
year = {{2022}},
}