The role of intestinal iron absorption machinery in regulating gut hormone secretion and systemic metabolism [Ileum]
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ABSTRACT:
PROVIDER: PRJNA716530 | ENA |
REPOSITORIES: ENA
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Project description:Bariatric surgeries remain the most effective treatments for sustained weight loss and remission of type 2 diabetes. In addition to decreased body weight and improved glucose regulation, these procedures also dramatically increase secretion of several gut hormones including GLP-1. Despite these benefits, there are deleterious side effects to these procedures that include an increased incidence of iron-deficiency related anemias. The transcription factor HIF2a is heavily expressed in the duodenum and regulates the molecular machinery of iron absorption from the lumen. Lower iron levels after both gastric bypass and sleeve gastrectomy procedures occur despite dramatic upregulation of HIF2a signaling in the duodenum and are likely the result of increased hepcidin levels. Low iron diets also stimulate increased HIF2a signaling in the duodenum and produce effects similar to bariatric surgery that include reduced body weight/fat, improved glucose regulation and increased secretion of the GLP-1. Gut-specific deletion of VHL results in a constitutive upregulation of HIF2a signaling in the small intestine and produces a dramatic phenotype that includes reduced body weight/fat, improved glucose tolerance and increased GLP-1 secretion from the intestine. These data demonstrate an important role of HIF2a signaling in the duodenum to regulate multiple aspects of systemic metabolism and gut hormone secretion pointing towards critical cross-talk between the systems that regulate iron and other aspects of systemic physiology important to prevalent metabolic diseases.
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Project description:Bariatric surgeries remain the most effective treatments for sustained weight loss and remission of type 2 diabetes. In addition to decreased body weight and improved glucose regulation, these procedures also dramatically increase secretion of several gut hormones including GLP-1. Despite these benefits, there are deleterious side effects to these procedures that include an increased incidence of iron-deficiency related anemias. The transcription factor HIF2a is heavily expressed in the duodenum and regulates the molecular machinery of iron absorption from the lumen. Lower iron levels after both gastric bypass and sleeve gastrectomy procedures occur despite dramatic upregulation of HIF2a signaling in the duodenum and are likely the result of increased hepcidin levels. Low iron diets also stimulate increased HIF2a signaling in the duodenum and produce effects similar to bariatric surgery that include reduced body weight/fat, improved glucose regulation and increased secretion of the GLP-1. Gut-specific deletion of VHL results in a constitutive upregulation of HIF2a signaling in the small intestine and produces a dramatic phenotype that includes reduced body weight/fat, improved glucose tolerance and increased GLP-1 secretion from the intestine. These data demonstrate an important role of HIF2a signaling in the duodenum to regulate multiple aspects of systemic metabolism and gut hormone secretion pointing towards critical cross-talk between the systems that regulate iron and other aspects of systemic physiology important to prevalent metabolic diseases.
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Project description:The role of intestinal iron absorption machinery in regulating gut hormone secretion and systemic metabolism [Duodenum]
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