دورية أكاديمية
أعرض في EDS

Impaired kisspeptin signaling decreases metabolism and promotes glucose intolerance and obesity.

التفاصيل البيبلوغرافية
العنوان: Impaired kisspeptin signaling decreases metabolism and promotes glucose intolerance and obesity.
المؤلفون: Tolson KP, Garcia C, Yen S, Simonds S, Stefanidis A, Lawrence A, Smith JT, Kauffman AS
المصدر: The Journal of clinical investigation [J Clin Invest] 2014 Jul; Vol. 124 (7), pp. 3075-9. Date of Electronic Publication: 2014 Jun 17.
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 Society for Clinical Investigation Country of Publication: United States NLM ID: 7802877 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1558-8238 (Electronic) Linking ISSN: 00219738 NLM ISO Abbreviation: J Clin Invest Subsets: MEDLINE
أسماء مطبوعة: Publication: 1999- : Ann Arbor, MI : American Society for Clinical Investigation
Original Publication: New Haven [etc.] American Society for Clinical Investigation.
مواضيع طبية MeSH: Glucose Intolerance/*etiology , Kisspeptins/*metabolism , Obesity/*etiology , Receptors, G-Protein-Coupled/*metabolism, Animals ; Body Weight ; Energy Metabolism ; Female ; Glucose Intolerance/metabolism ; Humans ; Male ; Mice ; Mice, 129 Strain ; Mice, Inbred C57BL ; Mice, Knockout ; Motor Activity ; Obesity/metabolism ; Ovariectomy ; Receptors, G-Protein-Coupled/deficiency ; Receptors, G-Protein-Coupled/genetics ; Receptors, Kisspeptin-1 ; Signal Transduction
مستخلص: The neuropeptide kisspeptin regulates reproduction by stimulating gonadotropin-releasing hormone (GnRH) neurons via the kisspeptin receptor KISS1R. In addition to GnRH neurons, KISS1R is expressed in other brain areas and peripheral tissues, which suggests that kisspeptin has additional functions beyond reproduction. Here, we studied the energetic and metabolic phenotype in mice lacking kisspeptin signaling (Kiss1r KO mice). Compared with WT littermates, adult Kiss1r KO females displayed dramatically higher BW, leptin levels, and adiposity, along with strikingly impaired glucose tolerance. Conversely, male Kiss1r KO mice had normal BW and glucose regulation. Surprisingly, despite their obesity, Kiss1r KO females ate less than WT females; however, Kiss1r KO females displayed markedly reduced locomotor activity, respiratory rate, and energy expenditure, which were not due to impaired thyroid hormone secretion. The BW and metabolic phenotype in Kiss1r KO females was not solely reflective of absent gonadal estrogen, as chronically ovariectomized Kiss1r KO females developed obesity, hyperleptinemia, reduced metabolism, and glucose intolerance compared with ovariectomized WT females. Our findings demonstrate that in addition to reproduction, kisspeptin signaling influences BW, energy expenditure, and glucose homeostasis in a sexually dimorphic and partially sex steroid-independent manner; therefore, alterations in kisspeptin signaling might contribute, directly or indirectly, to some facets of human obesity, diabetes, or metabolic dysfunction.
التعليقات: Comment in: J Clin Invest. 2014 Jul;124(7):2853-4. (PMID: 24937420)
Comment in: Nat Rev Endocrinol. 2014 Sep;10(9):511. (PMID: 24981460)
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معلومات مُعتمدة: P50 HD012303 United States HD NICHD NIH HHS; R01 HD065856 United States HD NICHD NIH HHS; T32 HD007203 United States HD NICHD NIH HHS; U54 HD012303 United States HD NICHD NIH HHS
المشرفين على المادة: 0 (Kiss1 protein, mouse)
0 (Kiss1r protein, mouse)
0 (Kisspeptins)
0 (Receptors, G-Protein-Coupled)
0 (Receptors, Kisspeptin-1)
تواريخ الأحداث: Date Created: 20140618 Date Completed: 20141006 Latest Revision: 20220317
رمز التحديث: 20240628
مُعرف محوري في PubMed: PMC4071390
DOI: 10.1172/JCI71075
PMID: 24937427
قاعدة البيانات: MEDLINE
الوصف
تدمد:1558-8238
DOI:10.1172/JCI71075