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

DSpace/Manakin Repository

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

Citable link to this page

 

 
Title: Fat-specific Dicer deficiency accelerates aging and mitigates several effects of dietary restriction in mice
Author: Reis, Felipe C. G.; Branquinho, Jéssica L. O.; Brandão, Bruna B.; Guerra, Beatriz A.; Silva, Ismael D.; Frontini, Andrea; Thomou, Thomas; Sartini, Loris; Cinti, Saverio; Kahn, C. Ronald; Festuccia, William T.; Kowaltowski, Alicia J.; Mori, Marcelo A.

Note: Order does not necessarily reflect citation order of authors.

Citation: Reis, F. C. G., J. L. O. Branquinho, B. B. Brandão, B. A. Guerra, I. D. Silva, A. Frontini, T. Thomou, et al. 2016. “Fat-specific Dicer deficiency accelerates aging and mitigates several effects of dietary restriction in mice.” Aging (Albany NY) 8 (6): 1201-1215. doi:10.18632/aging.100970. http://dx.doi.org/10.18632/aging.100970.
Full Text & Related Files:
Abstract: 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.
Published Version: doi:10.18632/aging.100970
Other Sources: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4931827/pdf/
Terms of Use: This article is made available under the terms and conditions applicable to Other Posted Material, as set forth at http://nrs.harvard.edu/urn-3:HUL.InstRepos:dash.current.terms-of-use#LAA
Citable link to this page: http://nrs.harvard.edu/urn-3:HUL.InstRepos:27822101
Downloads of this work:

Show full Dublin Core record

This item appears in the following Collection(s)

 
 

Search DASH


Advanced Search
 
 

Submitters