Gene expression of olfactory receptors in the murine small-intestine is affected by a high-fat diet and associated with enteroendocrine signalling
Mon-S1-004
Presented by: Rianne Evelien Jansen
Background: Enteroendocrine secretion is regulated by nutrient- and metabolite- sensing receptors in the intestinal lumen. Emerging evidence indicates the involvement of the GPCR family of olfactory receptors (ORs).
Objective: Identify nutrient sensing receptors involved in enteroendocrine signaling in metabolic health.
Methods: A 2-weeks controlled dietary intervention with a high-fat diet (HFD) and a low-fat diet (LDF) was performed in male C57BL/6J mice. Additionally, a chow-fed group was included. Differential gene expression, given in fold change (FC), was determined in mucosal scrapings of ten sections of the small intestine (SI) using Mouse genome 430 2.0 arrays.
Results: Comparing the HFD with the LFD group, 26 OR genes showed increased expression in the jejunum, whereas expression of five OR genes decreased in the jejunum and ileum. Notably, Olfr920 was downregulated in consecutive sections of the SI (FC range -1,65 to -1,43), with similar trends observed for Olfr111. The gene expression of the gut hormone somatostatin (SST) was downregulated in the jejunum (FC range -1.29 to -1.45). The differential expression patterns of Olfr920 and SST in response to the diet correlated strongly. Moreover, Olfr920 showed a high inverse correlation with fatty-acid binding protein 2 (fabp2). When comparing HFD with chow, Olfr558 was found to be upregulated in the duodenum, whereas a comparison between the LFD and chow showed that Olfr165 (the most highly expressed out of all ORs) was downregulated in the distal jejunum.
Conclusions: The HFD affected the gene expression of multiple OR family members, particularly Olfr920, Olfr111 and Olfr558. Through detailed sectioning of the SI we revealed that location-specific alterations in Olfr920 gene expression were associated with SST, a master regulatory gut hormone. The identification of nutrient sensing genes involved in HFD-induced pathogenesis may yield new GPCR-targets relevant to metabolic disorders, obesity and diabetes.
Objective: Identify nutrient sensing receptors involved in enteroendocrine signaling in metabolic health.
Methods: A 2-weeks controlled dietary intervention with a high-fat diet (HFD) and a low-fat diet (LDF) was performed in male C57BL/6J mice. Additionally, a chow-fed group was included. Differential gene expression, given in fold change (FC), was determined in mucosal scrapings of ten sections of the small intestine (SI) using Mouse genome 430 2.0 arrays.
Results: Comparing the HFD with the LFD group, 26 OR genes showed increased expression in the jejunum, whereas expression of five OR genes decreased in the jejunum and ileum. Notably, Olfr920 was downregulated in consecutive sections of the SI (FC range -1,65 to -1,43), with similar trends observed for Olfr111. The gene expression of the gut hormone somatostatin (SST) was downregulated in the jejunum (FC range -1.29 to -1.45). The differential expression patterns of Olfr920 and SST in response to the diet correlated strongly. Moreover, Olfr920 showed a high inverse correlation with fatty-acid binding protein 2 (fabp2). When comparing HFD with chow, Olfr558 was found to be upregulated in the duodenum, whereas a comparison between the LFD and chow showed that Olfr165 (the most highly expressed out of all ORs) was downregulated in the distal jejunum.
Conclusions: The HFD affected the gene expression of multiple OR family members, particularly Olfr920, Olfr111 and Olfr558. Through detailed sectioning of the SI we revealed that location-specific alterations in Olfr920 gene expression were associated with SST, a master regulatory gut hormone. The identification of nutrient sensing genes involved in HFD-induced pathogenesis may yield new GPCR-targets relevant to metabolic disorders, obesity and diabetes.