دورية أكاديمية
Krüppel-like factor 4 in transcriptional control of the three unique isoforms of Agouti-related peptide in mice.
| العنوان: | Krüppel-like factor 4 in transcriptional control of the three unique isoforms of Agouti-related peptide in mice. |
|---|---|
| المؤلفون: | Ritter ML; Department of Physiology, Medical College of Wisconsin, Milwaukee, Wisconsin, United States., Wagner VA; Department of Physiology, Medical College of Wisconsin, Milwaukee, Wisconsin, United States.; Genetics Graduate Program, University of Iowa, Iowa City, Iowa, United States., Balapattabi K; Department of Physiology, Medical College of Wisconsin, Milwaukee, Wisconsin, United States., Opichka MA; Department of Physiology, Medical College of Wisconsin, Milwaukee, Wisconsin, United States., Lu KT; Department of Physiology, Medical College of Wisconsin, Milwaukee, Wisconsin, United States., Wackman KK; Department of Physiology, Medical College of Wisconsin, Milwaukee, Wisconsin, United States., Reho JJ; Department of Physiology, Medical College of Wisconsin, Milwaukee, Wisconsin, United States.; Comprehensive Rodent Metabolic Phenotyping Core, Medical College of Wisconsin, Milwaukee, Wisconsin, United States., Keen HL; Bioinformatics Division, Institute of Human Genetics, University of Iowa, Iowa City, Iowa, United States., Kwitek AE; Department of Physiology, Medical College of Wisconsin, Milwaukee, Wisconsin, United States.; Department of Biomedical Engineering, Medical College of Wisconsin, Milwaukee, Wisconsin, United States.; Cardiovascular Center, Medical College of Wisconsin, Milwaukee, Wisconsin, United States.; Linda T. and John A. Mellowes Center for Genomic Sciences and Precision Medicine, Medical College of Wisconsin, Milwaukee, Wisconsin, United States., Morselli LL; Cardiovascular Center, Medical College of Wisconsin, Milwaukee, Wisconsin, United States.; Division of Endocrinology and Molecular Medicine, Department of Medicine, Medical College of Wisconsin, Milwaukee, Wisconsin, United States., Geurts AM; Department of Physiology, Medical College of Wisconsin, Milwaukee, Wisconsin, United States.; Cardiovascular Center, Medical College of Wisconsin, Milwaukee, Wisconsin, United States.; Linda T. and John A. Mellowes Center for Genomic Sciences and Precision Medicine, Medical College of Wisconsin, Milwaukee, Wisconsin, United States., Sigmund CD; Department of Physiology, Medical College of Wisconsin, Milwaukee, Wisconsin, United States.; Cardiovascular Center, Medical College of Wisconsin, Milwaukee, Wisconsin, United States.; Neuroscience Research Center, Medical College of Wisconsin, Milwaukee, Wisconsin, United States., Grobe JL; Department of Physiology, Medical College of Wisconsin, Milwaukee, Wisconsin, United States.; Comprehensive Rodent Metabolic Phenotyping Core, Medical College of Wisconsin, Milwaukee, Wisconsin, United States.; Department of Biomedical Engineering, Medical College of Wisconsin, Milwaukee, Wisconsin, United States.; Cardiovascular Center, Medical College of Wisconsin, Milwaukee, Wisconsin, United States.; Neuroscience Research Center, Medical College of Wisconsin, Milwaukee, Wisconsin, United States. |
| المصدر: | Physiological genomics [Physiol Genomics] 2024 Mar 01; Vol. 56 (3), pp. 265-275. Date of Electronic Publication: 2023 Dec 25. |
| نوع المنشور: | Journal Article |
| اللغة: | English |
| بيانات الدورية: | Publisher: American Physiological Society Country of Publication: United States NLM ID: 9815683 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1531-2267 (Electronic) Linking ISSN: 10948341 NLM ISO Abbreviation: Physiol Genomics Subsets: MEDLINE |
| أسماء مطبوعة: | Original Publication: Bethesda, MD : American Physiological Society, c1999- |
| مواضيع طبية MeSH: | Agouti-Related Protein*/genetics , Agouti-Related Protein*/metabolism , Kruppel-Like Factor 4* , Neurons*/metabolism, Animals ; Mice ; Hypothalamus/metabolism ; Obesity/genetics ; Obesity/metabolism ; Protein Isoforms/genetics ; Protein Isoforms/metabolism |
| مستخلص: | Agouti-related peptide (AgRP/ Agrp ) within the hypothalamic arcuate nucleus (ARC) contributes to the control of energy balance, and dysregulated Agrp may contribute to metabolic adaptation during prolonged obesity. In mice, three isoforms of Agrp are encoded via distinct first exons. Agrp-A (ENSMUST00000005849.11) contributed 95% of total Agrp in mouse ARC, whereas Agrp-B (ENSMUST00000194654.2) dominated in placenta (73%). Conditional deletion of Klf4 from Agrp -expressing cells ( Klf4 Agrp -KO mice) reduced Agrp mRNA and increased energy expenditure but had no effects on food intake or the relative abundance of Agrp isoforms in the ARC. Chronic high-fat diet feeding masked these effects of Klf4 deletion, highlighting the context-dependent contribution of KLF4 to Agrp control. In the GT1-7 mouse hypothalamic cell culture model, which expresses all three isoforms of Agrp (including Agrp-C , ENSMUST00000194091.6), inhibition of extracellular signal-regulated kinase (ERK) simultaneously increased KLF4 binding to the Agrp promoter and stimulated Agrp expression. In addition, siRNA-mediated knockdown of Klf4 reduced expression of Agrp . We conclude that the expression of individual isoforms of Agrp in the mouse is dependent upon cell type and that KLF4 directly promotes the transcription of Agrp via a mechanism that is superseded during obesity. NEW & NOTEWORTHY In mice, three distinct isoforms of Agouti-related peptide are encoded via distinct first exons. In the arcuate nucleus of the hypothalamus, Krüppel-like factor 4 stimulates transcription of the dominant isoform in lean mice, but this mechanism is altered during diet-induced obesity. |
| References: | Curr Hypertens Rep. 2018 Mar 19;20(3):25. (PMID: 29556733) Neuroendocrinology. 2021;111(7):678-695. (PMID: 32575098) Endocrinology. 2006 Sep;147(9):4486-95. (PMID: 16763061) Regul Pept. 2012 Jan 10;173(1-3):13-20. (PMID: 21903140) Int J Biochem Cell Biol. 2000 Nov-Dec;32(11-12):1103-21. (PMID: 11137451) Front Endocrinol (Lausanne). 2023 Feb 01;14:1121829. (PMID: 36817590) Nucleic Acids Res. 2022 Jan 7;50(D1):D316-D325. (PMID: 34751401) Nat Genet. 1999 Aug;22(4):356-60. (PMID: 10431239) Nutrition. 2007 Sep;23(9):665-71. (PMID: 17643264) Nucleic Acids Res. 2015 Feb 27;43(4):e27. (PMID: 25477382) Hypertension. 2020 Aug;76(2):589-597. (PMID: 32507042) Dev Biol. 2011 Jan 15;349(2):310-20. (PMID: 21070761) Obesity (Silver Spring). 2019 May;27(5):793-802. (PMID: 30938081) Hypertension. 2020 Feb;75(2):569-579. (PMID: 31865781) J Neurophysiol. 1995 Jan;73(1):56-64. (PMID: 7714589) Endocrinology. 2016 Apr;157(4):1457-66. (PMID: 26889940) Endocr Regul. 2009 Jul;43(3):99-106. (PMID: 19817504) Endocrine. 2016 Sep;53(3):839-47. (PMID: 26979526) Am J Physiol Regul Integr Comp Physiol. 2022 Oct 1;323(4):R410-R421. (PMID: 35816717) Nucleic Acids Res. 2020 Jan 8;48(D1):D87-D92. (PMID: 31701148) Reprod Biol Endocrinol. 2008 Apr 02;6:14. (PMID: 18384674) J Am Assoc Lab Anim Sci. 2022 Mar 1;61(2):132-139. (PMID: 34996529) J Clin Invest. 2022 Oct 3;132(19):. (PMID: 36189793) Int J Obes (Lond). 2017 Jan;41(1):149-158. (PMID: 27773938) Cell Rep. 2023 Aug 29;42(8):112935. (PMID: 37540598) Neuron. 1990 Jul;5(1):1-10. (PMID: 2196069) Mol Cell Endocrinol. 2022 Jul 15;552:111630. (PMID: 35569583) Endocrinology. 2010 Oct;151(10):4745-55. (PMID: 20826561) Mol Metab. 2012 Jul 26;1(1-2):61-9. (PMID: 24024119) Peptides. 2009 Feb;30(2):181-90. (PMID: 19059445) Nat Neurosci. 2017 Mar;20(3):484-496. (PMID: 28166221) J Biol Chem. 1996 Aug 16;271(33):20009-17. (PMID: 8702718) J Nutr. 2004 Jun;134(6):1369-74. (PMID: 15173398) Hypertension. 2021 Apr;77(4):1061-1068. (PMID: 33611936) Nucleic Acids Res. 2018 Jan 4;46(D1):D267-D275. (PMID: 29126285) J Endocrinol. 2009 Jul;202(1):35-41. (PMID: 19403567) Endocrinology. 2000 Jun;141(6):2012-7. (PMID: 10830284) Front Physiol. 2022 Feb 25;13:855054. (PMID: 35283781) Am J Physiol Endocrinol Metab. 2002 Jun;282(6):E1352-9. (PMID: 12006366) Obesity (Silver Spring). 2016 Jun;24(6):1299-304. (PMID: 27130070) J Clin Invest. 2023 Apr 3;133(7):. (PMID: 36787185) Methods. 2001 Dec;25(4):402-8. (PMID: 11846609) Cell. 2007 Nov 30;131(5):861-72. (PMID: 18035408) Am J Physiol Endocrinol Metab. 2009 Dec;297(6):E1247-59. (PMID: 19724019) Nat Methods. 2017 Apr;14(4):417-419. (PMID: 28263959) Nucleic Acids Res. 2020 Jan 8;48(D1):D180-D188. (PMID: 31665499) Diabetes. 2011 Jan;60(1):97-106. (PMID: 20980461) FEBS J. 2022 Apr;289(8):2362-2381. (PMID: 34469623) Mol Metab. 2014 Apr 15;3(4):441-51. (PMID: 24944903) Behav Brain Res. 2009 Dec 14;205(1):50-6. (PMID: 19616032) Endocrinology. 2004 May;145(5):2375-83. (PMID: 14736732) Am J Physiol Regul Integr Comp Physiol. 2020 May 1;318(5):R855-R869. (PMID: 32186897) Nucleic Acids Res. 2022 Jan 7;50(D1):D165-D173. (PMID: 34850907) Diabetes. 2009 Mar;58(3):536-42. (PMID: 19066310) |
| معلومات مُعتمدة: | R01 HL134850 United States HL NHLBI NIH HHS; T32 HL007638 United States HL NHLBI NIH HHS; R35 HL144807 United States HL NHLBI NIH HHS; P01 HL084207 United States HL NHLBI NIH HHS; R01 DK133121 United States DK NIDDK NIH HHS; UL1 TR001436 United States TR NCATS NIH HHS |
| فهرسة مساهمة: | Keywords: Agouti-related peptide; Kruppël-like factor 4; energy expenditure; metabolism; obesity |
| المشرفين على المادة: | 0 (Agouti-Related Protein) 0 (Kruppel-Like Factor 4) 0 (Protein Isoforms) 0 (Agrp protein, mouse) |
| تواريخ الأحداث: | Date Created: 20231225 Date Completed: 20240215 Latest Revision: 20240628 |
| رمز التحديث: | 20240628 |
| مُعرف محوري في PubMed: | PMC10866620 |
| DOI: | 10.1152/physiolgenomics.00042.2023 |
| PMID: | 38145289 |
| قاعدة البيانات: | MEDLINE |
| تدمد: | 1531-2267 |
|---|---|
| DOI: | 10.1152/physiolgenomics.00042.2023 |