دورية أكاديمية
Conditional knockout of kisspeptin signaling in brown adipose tissue increases metabolic rate and body temperature and lowers body weight.
| العنوان: | Conditional knockout of kisspeptin signaling in brown adipose tissue increases metabolic rate and body temperature and lowers body weight. |
|---|---|
| المؤلفون: | Tolson KP; Department of OBGYN and Reproductive Sciences, University of California, San Diego, CA, USA., Marooki N; Department of OBGYN and Reproductive Sciences, University of California, San Diego, CA, USA., De Bond JP; School of Human Sciences, University of Western Australia, Perth, WA, Australia., Walenta E; Department of Medicine, University of California, San Diego, CA, USA., Stephens SBZ; Department of OBGYN and Reproductive Sciences, University of California, San Diego, CA, USA., Liaw RB; Department of OBGYN and Reproductive Sciences, University of California, San Diego, CA, USA., Savur R; Department of OBGYN and Reproductive Sciences, University of California, San Diego, CA, USA., Wolfe A; Department of Pediatrics and Physiology, Johns Hopkins University, Baltimore, MD, USA., Oh DY; Department of Medicine, University of California, San Diego, CA, USA., Smith JT; School of Human Sciences, University of Western Australia, Perth, WA, Australia., Kauffman AS; Department of OBGYN and Reproductive Sciences, University of California, San Diego, CA, USA. |
| المصدر: | FASEB journal : official publication of the Federation of American Societies for Experimental Biology [FASEB J] 2020 Jan; Vol. 34 (1), pp. 107-121. Date of Electronic Publication: 2019 Nov 19. |
| نوع المنشور: | Journal Article |
| اللغة: | English |
| بيانات الدورية: | Publisher: Federation of American Societies for Experimental Biology Country of Publication: United States NLM ID: 8804484 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1530-6860 (Electronic) Linking ISSN: 08926638 NLM ISO Abbreviation: FASEB J Subsets: MEDLINE |
| أسماء مطبوعة: | Publication: 2020- : [Bethesda, Md.] : Hoboken, NJ : Federation of American Societies for Experimental Biology ; Wiley Original Publication: [Bethesda, Md.] : The Federation, [c1987- |
| مواضيع طبية MeSH: | Adipocytes, Brown/*metabolism , Body Temperature/*physiology , Body Weight/*physiology , Energy Metabolism/*genetics , Energy Metabolism/*physiology , Receptors, Kisspeptin-1/*metabolism, Animals ; Body Temperature/genetics ; Body Weight/genetics ; Genotype ; Mice ; Mice, Knockout ; Receptors, Kisspeptin-1/genetics |
| مستخلص: | The peptide kisspeptin and its receptor, Kiss1r, act centrally to stimulate reproduction. Evidence indicates that kisspeptin signaling is also important for body weight (BW) and metabolism. We recently reported that Kiss1r KO mice develop obesity, along with reduced metabolism and energy expenditure, independent of estradiol levels. Outside the brain, Kiss1r is expressed in several metabolic tissues, including brown adipose tissue (BAT), but it is unknown which specific tissue is responsible for the metabolic phenotype in Kiss1r KOs. We first determined that global Kiss1r KO mice have significant alterations in body temperature and BAT thermogenic gene expression, perhaps contributing to their obesity. Next, to test whether kisspeptin signaling specifically in BAT influences BW, metabolism, or body temperature, we used Cre/lox technology to generate conditional Kiss1r knockout exclusively in BAT (BAT-Kiss1r KO). Unlike global Kiss1r KOs, BAT-Kiss1r KOs (lacking Kiss1r in just BAT) were not hypogonadal, as expected. Surprisingly, however, BAT-Kiss1r KOs of both sexes displayed significantly lower BW and adiposity than controls. This novel BAT-Kiss1r KO phenotype was of greater magnitude in females and was associated with improved glucose tolerance, increased metabolism, energy expenditure, and locomotor activity, along with increased body temperature and BAT gene expression, specifically Cox8b. Our findings suggest that the previously observed obesity and decreased metabolism in global Kiss1r KOs reflect impaired kisspeptin signaling in non-BAT tissues. However, the novel finding of increased metabolism and body temperature and lower BW in BAT-Kiss1r KOs reveal a previously unidentified role for endogenous kisspeptin signaling in BAT in modulating metabolic and thermogenic physiology. (© 2019 Federation of American Societies for Experimental Biology.) |
| References: | Eur J Endocrinol. 1997 Mar;136(3):251-64. (PMID: 9100546) J Cereb Blood Flow Metab. 2004 Jul;24(7):780-8. (PMID: 15241186) Neuropeptides. 2016 Apr;56:41-9. (PMID: 26853724) J Clin Invest. 2014 Jul;124(7):3075-9. (PMID: 24937427) Proc Natl Acad Sci U S A. 2014 Jul 15;111(28):10335-40. (PMID: 24982149) Cell Metab. 2007 Jul;6(1):38-54. (PMID: 17618855) Endocrinology. 2016 Nov;157(11):4192-4199. (PMID: 27649089) Endocrine. 2017 Apr;56(1):54-64. (PMID: 28194651) Cell Metab. 2014 Apr 1;19(4):667-81. (PMID: 24703698) J Neural Transm (Vienna). 2006 Oct;113(10):1383-93. (PMID: 16465460) Mol Endocrinol. 2014 Feb;28(2):225-38. (PMID: 24422632) Peptides. 2009 Jan;30(1):34-41. (PMID: 18571287) Int J Obes (Lond). 2010 Oct;34 Suppl 1:S17-22. (PMID: 20935660) Biol Reprod. 2013 Jun 13;88(6):146. (PMID: 23595904) Proc Natl Acad Sci U S A. 2005 Feb 1;102(5):1761-6. (PMID: 15665093) Mol Cell Endocrinol. 2010 Aug 5;324(1-2):51-63. (PMID: 20083160) Mol Cell Endocrinol. 2019 Dec 1;498:110559. (PMID: 31442544) J Biol Chem. 2001 Sep 14;276(37):34631-6. (PMID: 11457843) Endocrinology. 2018 Nov 1;159(11):3723-3736. (PMID: 30272161) Nat Rev Endocrinol. 2016 Aug;12(8):452-66. (PMID: 27199290) J Neuroendocrinol. 2016 Oct;28(10):. (PMID: 27601011) Nature. 2001 May 31;411(6837):613-7. (PMID: 11385580) Endocr Rev. 2009 Oct;30(6):713-43. (PMID: 19770291) Proc Natl Acad Sci U S A. 2015 Feb 3;112(5):1607-12. (PMID: 25605929) J Appl Physiol (1985). 2002 May;92(5):2187-98. (PMID: 11960973) J Biol Chem. 2001 Aug 3;276(31):28969-75. (PMID: 11387329) Endocrinology. 2010 Jan;151(1):312-21. (PMID: 19966188) |
| معلومات مُعتمدة: | R01 HD068777 United States HD NICHD NIH HHS; T32 HD007203 United States HD NICHD NIH HHS; R01 HD090161 United States HD NICHD NIH HHS; R01 DK108773 United States DK NIDDK NIH HHS; P50 HD012303 United States HD NICHD NIH HHS; R01 HD082567 United States HD NICHD NIH HHS; R00 HD092894 United States HD NICHD NIH HHS; K99 HD092894 United States HD NICHD NIH HHS; F32 HD076606 United States HD NICHD NIH HHS; P30 DK063491 United States DK NIDDK NIH HHS; U01 HD066432 United States HD NICHD NIH HHS |
| فهرسة مساهمة: | Keywords: BAT; GPR54; Kiss1; Kiss1r; adipose; fat; kisspeptin; metabolism; obesity; temperature |
| المشرفين على المادة: | 0 (Kiss1r protein, mouse) 0 (Receptors, Kisspeptin-1) |
| تواريخ الأحداث: | Date Created: 20200110 Date Completed: 20200713 Latest Revision: 20200713 |
| رمز التحديث: | 20240628 |
| مُعرف محوري في PubMed: | PMC7202476 |
| DOI: | 10.1096/fj.201901600R |
| PMID: | 31914628 |
| قاعدة البيانات: | MEDLINE |
| تدمد: | 1530-6860 |
|---|---|
| DOI: | 10.1096/fj.201901600R |