Reis 2016 Aging (Albany NY)

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Reis FC, Branquinho JL, Brandão BB, Guerra BA, Silva ID, Frontini A, Thomou T, Sartini L, Cinti S, Kahn CR, Festuccia WT, Kowaltowski AJ, Mori MA (2016) Fat-specific Dicer deficiency accelerates aging and mitigates several effects of dietary restriction in mice. Aging (Albany NY) 8:1201-22.

» PMID: 27241713 Open Access

Reis FC, Branquinho JL, Brandao BB, Guerra BA, Silva ID, Frontini A, Thomou T, Sartini L, Cinti S, Kahn CR, Festuccia WT, Kowaltowski AJ, Mori MA (2016) Aging (Albany NY)

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.

Keywords: Adipose tissue, Aging, Dicer, Dietary restriction, Insulin resistance

O2k-Network Lab: BR Sao Paulo Kowaltowski AJ


Labels: MiParea: Respiration, Genetic knockout;overexpression, Exercise physiology;nutrition;life style  Pathology: Aging;senescence, Diabetes 

Organism: Mouse  Tissue;cell: Fat  Preparation: Permeabilized cells 


Coupling state: LEAK  Pathway: N, S, ROX  HRR: Oxygraph-2k 

2016-07