دورية أكاديمية
أعرض في EDS

Fat-specific Dicer deficiency accelerates aging and mitigates several effects of dietary restriction in mice.

التفاصيل البيبلوغرافية
العنوان: Fat-specific Dicer deficiency accelerates aging and mitigates several effects of dietary restriction in mice.
المؤلفون: Reis FC; Department of Biophysics, Escola Paulista de Medicina, Universidade Federal de São Paulo, São Paulo, Brazil., Branquinho JL; Department of Biophysics, Escola Paulista de Medicina, Universidade Federal de São Paulo, São Paulo, Brazil., Brandão BB; Department of Biophysics, Escola Paulista de Medicina, Universidade Federal de São Paulo, São Paulo, Brazil., Guerra BA; Department of Biophysics, Escola Paulista de Medicina, Universidade Federal de São Paulo, São Paulo, Brazil., Silva ID; Department of Gynecology, Escola Paulista de Medicina, Universidade Federal de São Paulo, São Paulo, Brazil., Frontini A; Department of Public Health, Experimental and Forensic Medicine, University of Pavia, Pavia, Italy., Thomou T; Section on Integrative Physiology and Metabolism, Joslin Diabetes Center, Harvard Medical School, Boston, MA 02215, USA., Sartini L; Department of Clinical and Experimental Medicine, Università Politecnica delle Marche, Ancona, Italy., Cinti S; Department of Clinical and Experimental Medicine, Università Politecnica delle Marche, Ancona, Italy., Kahn CR; Section on Integrative Physiology and Metabolism, Joslin Diabetes Center, Harvard Medical School, Boston, MA 02215, USA., Festuccia WT; Departament of Physiology, Instituto de Ciências Biomédicas, Universidade de São Paulo, São Paulo, Brazil., Kowaltowski AJ; Department of Biochemistry, Instituto de Química, Universidade de São Paulo, São Paulo, Brazil., Mori MA; Department of Biophysics, Escola Paulista de Medicina, Universidade Federal de São Paulo, São Paulo, Brazil.; Department of Biochemistry and Tissue Biology, Instituto de Biologia, Universidade Estadual de Campinas, Campinas, Brazil.
المصدر: Aging [Aging (Albany NY)] 2016 Jun; Vol. 8 (6), pp. 1201-22.
نوع المنشور: Journal Article; Research Support, Non-U.S. Gov't
اللغة: English
بيانات الدورية: Publisher: Impact Journals, LLC Country of Publication: United States NLM ID: 101508617 Publication Model: Print Cited Medium: Internet ISSN: 1945-4589 (Electronic) Linking ISSN: 19454589 NLM ISO Abbreviation: Aging (Albany NY) Subsets: MEDLINE
أسماء مطبوعة: Original Publication: Albany, NY : Impact Journals, LLC
مواضيع طبية MeSH: Adipose Tissue, White/*metabolism , Aging/*metabolism , DEAD-box RNA Helicases/*metabolism , Energy Metabolism/*physiology , Insulin Resistance/*physiology , Longevity/*genetics , Ribonuclease III/*metabolism, Adipose Tissue, White/drug effects ; Aging/genetics ; Animals ; DEAD-box RNA Helicases/genetics ; Energy Metabolism/drug effects ; Longevity/drug effects ; Mechanistic Target of Rapamycin Complex 1/metabolism ; Metabolomics ; Mice ; Mice, Knockout ; Mitochondria/metabolism ; Muscle, Skeletal/drug effects ; Muscle, Skeletal/metabolism ; Ribonuclease III/genetics ; Sirolimus/pharmacology
مستخلص: Aging increases the risk of type 2 diabetes, and this can be prevented by dietary restriction (DR). We have previously shown that DR inhibits the downregulation of miRNAs and their processing enzymes - mainly Dicer - that occurs with aging in mouse white adipose tissue (WAT). Here we used fat-specific Dicer knockout mice (AdicerKO) to understand the contributions of adipose tissue Dicer to the metabolic effects of aging and DR. Metabolomic data uncovered a clear distinction between the serum metabolite profiles of Lox control and AdicerKO mice, with a notable elevation of branched-chain amino acids (BCAA) in AdicerKO. These profiles were associated with reduced oxidative metabolism and increased lactate in WAT of AdicerKO mice and were accompanied by structural and functional changes in mitochondria, particularly under DR. AdicerKO mice displayed increased mTORC1 activation in WAT and skeletal muscle, where Dicer expression is not affected. This was accompanied by accelerated age-associated insulin resistance and premature mortality. Moreover, DR-induced insulin sensitivity was abrogated in AdicerKO mice. This was reverted by rapamycin injection, demonstrating that insulin resistance in AdicerKO mice is caused by mTORC1 hyperactivation. Our study evidences a DR-modulated role for WAT Dicer in controlling metabolism and insulin resistance.
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فهرسة مساهمة: Keywords: adipose tissue; aging; dicer; dietary restriction; insulin resistance
المشرفين على المادة: EC 2.7.11.1 (Mechanistic Target of Rapamycin Complex 1)
EC 3.1.26.3 (Dicer1 protein, mouse)
EC 3.1.26.3 (Ribonuclease III)
EC 3.6.4.13 (DEAD-box RNA Helicases)
W36ZG6FT64 (Sirolimus)
تواريخ الأحداث: Date Created: 20160601 Date Completed: 20171116 Latest Revision: 20181113
رمز التحديث: 20240628
مُعرف محوري في PubMed: PMC4931827
DOI: 10.18632/aging.100970
PMID: 27241713
قاعدة البيانات: MEDLINE
الوصف
تدمد:1945-4589
DOI:10.18632/aging.100970