BMC Med. 2022 Nov 11;20(1):440. doi: 10.1186/s12916-022-02635-3.

Olof Karlson ¹, Henrik Arnell ^2 3, Audur H Gudjonsdottir ⁴, Daniel Agardh ⁵, Åsa Torinsson Naluai ⁶

Author information

¹Department of Laboratory Medicine, Institute of Biomedicine, Sahlgrenska Academy at the University of Gothenburg, Gothenburg, Sweden.

²Department of Pediatric Gastroenterology, Hepatology and Nutrition, Astrid Lindgren Children's Hospital, Karolinska University Hospital, Stockholm, Sweden.

³Department of Women's and Children's Health, Karolinska Institute, Stockholm, Sweden.

⁴Department of Paediatric Gastroenterology, Hepatology and Nutrition, Queen Silvia Children's Hospital, Sahlgrenska University Hospital, Gothenburg, Sweden.

⁵Department of Clinical Sciences, Unit of Celiac Disease and Diabetes, Lund University, Malmö, Sweden.

⁶Department of Laboratory Medicine, Institute of Biomedicine, Sahlgrenska Academy at the University of Gothenburg, Gothenburg, Sweden. asa.torinsson.naluai@gu.se.

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 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.