دورية أكاديمية
The short-chain fatty acid receptor, FFA2, contributes to gestational glucose homeostasis.
| العنوان: | The short-chain fatty acid receptor, FFA2, contributes to gestational glucose homeostasis. |
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| المؤلفون: | Fuller M; Division of Endocrinology, Metabolism and Molecular Medicine, Northwestern University Feinberg School of Medicine, Chicago, Illinois;, Priyadarshini M; Division of Endocrinology, Metabolism and Molecular Medicine, Northwestern University Feinberg School of Medicine, Chicago, Illinois;, Gibbons SM; Graduate Program in Biophysical Sciences, University of Chicago, Chicago, Illinois; Institute for Genomic and Systems Biology, Argonne National Laboratory, Argonne, Illinois;, Angueira AR; Division of Endocrinology, Metabolism and Molecular Medicine, Northwestern University Feinberg School of Medicine, Chicago, Illinois;, Brodsky M; Division of Endocrinology, Metabolism and Molecular Medicine, Northwestern University Feinberg School of Medicine, Chicago, Illinois;, Hayes MG; Division of Endocrinology, Metabolism and Molecular Medicine, Northwestern University Feinberg School of Medicine, Chicago, Illinois;, Kovatcheva-Datchary P; Wallenberg Laboratory, Department of Molecular and Clinical Medicine, University of Gothenburg, Gothenburg, Sweden;, Bäckhed F; Wallenberg Laboratory, Department of Molecular and Clinical Medicine, University of Gothenburg, Gothenburg, Sweden;, Gilbert JA; Graduate Program in Biophysical Sciences, University of Chicago, Chicago, Illinois; Institute for Genomic and Systems Biology, Argonne National Laboratory, Argonne, Illinois; Department of Ecology and Evolution, University of Chicago, Chicago, Illinois; Marine Biological Laboratory, Woods Hole, Massachusetts; College of Environmental and Resource Sciences, Zhejiang University, Hangzhou, China; Department of Surgery, University of Chicago, Chicago, Illinois; and., Lowe WL Jr; Division of Endocrinology, Metabolism and Molecular Medicine, Northwestern University Feinberg School of Medicine, Chicago, Illinois;, Layden BT; Division of Endocrinology, Metabolism and Molecular Medicine, Northwestern University Feinberg School of Medicine, Chicago, Illinois; Jesse Brown Veterans Affairs Medical Center, Chicago, Illinois b-layden@northwestern.edu. |
| المصدر: | American journal of physiology. Endocrinology and metabolism [Am J Physiol Endocrinol Metab] 2015 Nov 15; Vol. 309 (10), pp. E840-51. Date of Electronic Publication: 2015 Sep 22. |
| نوع المنشور: | Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, Non-P.H.S. |
| اللغة: | English |
| بيانات الدورية: | Publisher: American Physiological Society Country of Publication: United States NLM ID: 100901226 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1522-1555 (Electronic) Linking ISSN: 01931849 NLM ISO Abbreviation: Am J Physiol Endocrinol Metab Subsets: MEDLINE |
| أسماء مطبوعة: | Original Publication: Bethesda, MD. : American Physiological Society |
| مواضيع طبية MeSH: | Gastrointestinal Microbiome*, Diabetes, Gestational/*metabolism , Fatty Acids, Volatile/*metabolism , Insulin/*metabolism , Insulin-Secreting Cells/*metabolism , Receptors, Cell Surface/*metabolism, Actinobacteria/classification ; Actinobacteria/growth & development ; Actinobacteria/isolation & purification ; Actinobacteria/metabolism ; Animals ; Bacteroidetes/classification ; Bacteroidetes/growth & development ; Bacteroidetes/isolation & purification ; Bacteroidetes/metabolism ; Cecum/metabolism ; Cecum/microbiology ; Diabetes, Gestational/blood ; Diabetes, Gestational/microbiology ; Fatty Acids, Volatile/blood ; Female ; Fermentation ; Gastrointestinal Contents/chemistry ; Gastrointestinal Contents/microbiology ; Insulin/blood ; Insulin Secretion ; Mice, Inbred C57BL ; Mice, Knockout ; Molecular Typing ; Pregnancy ; Pregnancy Maintenance ; Principal Component Analysis ; Receptors, Cell Surface/agonists ; Receptors, Cell Surface/genetics ; Tenericutes/classification ; Tenericutes/growth & development ; Tenericutes/isolation & purification ; Tenericutes/metabolism ; Tissue Culture Techniques |
| مستخلص: | The structure of the human gastrointestinal microbiota can change during pregnancy, which may influence gestational metabolism; however, a mechanism of action remains unclear. Here we observed that in wild-type (WT) mice the relative abundance of Actinobacteria and Bacteroidetes increased during pregnancy. Along with these changes, short-chain fatty acids (SCFAs), which are mainly produced through gut microbiota fermentation, significantly changed in both the cecum and peripheral blood throughout gestation in these mice. SCFAs are recognized by G protein-coupled receptors (GPCRs) such as free fatty acid receptor-2 (FFA2), and we have previously demonstrated that the fatty acid receptor-2 gene (Ffar2) expression is higher in pancreatic islets during pregnancy. Using female Ffar2-/- mice, we explored the physiological relevance of signaling through this GPCR and found that Ffar2-deficient female mice developed fasting hyperglycemia and impaired glucose tolerance in the setting of impaired insulin secretion compared with WT mice during, but not before, pregnancy. Insulin tolerance tests were similar in Ffar2-/- and WT mice before and during pregnancy. Next, we examined the role of FFA2 in gestational β-cell mass, observing that Ffar2-/- mice had diminished gestational expansion of β-cells during pregnancy. Interestingly, mouse genotype had no significant impact on the composition of the gut microbiome, but did affect the observed SCFA profiles, suggesting a functional difference in the microbiota. Together, these results suggest a potential link between increased Ffar2 expression in islets and the alteration of circulating SCFA levels, possibly explaining how changes in the gut microbiome contribute to gestational glucose homeostasis. |
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| معلومات مُعتمدة: | P30 DK-020595 United States DK NIDDK NIH HHS; R01 DK104927 United States DK NIDDK NIH HHS; 5T-32EB-009412 United States EB NIBIB NIH HHS; K12-HD-44405 United States HD NICHD NIH HHS; IK2 BX001587 United States BX BLRD VA; R25 GM079300 United States GM NIGMS NIH HHS; T32 EB009412 United States EB NIBIB NIH HHS; I01 BX003382 United States BX BLRD VA; P30 DK020595 United States DK NIDDK NIH HHS |
| فهرسة مساهمة: | Keywords: free fatty acid receptor-2; gut microbiome; islets |
| المشرفين على المادة: | 0 (Fatty Acids, Volatile) 0 (Insulin) 0 (Receptors, Cell Surface) 0 (free fatty acid 2 receptor, mouse) |
| تواريخ الأحداث: | Date Created: 20150924 Date Completed: 20160307 Latest Revision: 20220408 |
| رمز التحديث: | 20240628 |
| مُعرف محوري في PubMed: | PMC4838121 |
| DOI: | 10.1152/ajpendo.00171.2015 |
| PMID: | 26394664 |
| قاعدة البيانات: | MEDLINE |
| تدمد: | 1522-1555 |
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| DOI: | 10.1152/ajpendo.00171.2015 |