RRC ID 57336
著者 Yan Y, Wang H, Hu M, Jiang L, Wang Y, Liu P, Liang X, Liu J, Li C, Lindström-Battle A, Lam SM, Shui G, Deng WM, Jiao R.
タイトル HDAC6 Suppresses Age-Dependent Ectopic Fat Accumulation by Maintaining the Proteostasis of PLIN2 in Drosophila.
ジャーナル Dev Cell
Abstract Age-dependent ectopic fat accumulation (EFA) in animals contributes to the progression of tissue aging and diseases such as obesity, diabetes, and cancer. However, the primary causes of age-dependent EFA remain largely elusive. Here, we characterize the occurrence of age-dependent EFA in Drosophila and identify HDAC6, a cytosolic histone deacetylase, as a suppressor of EFA. Loss of HDAC6 leads to significant age-dependent EFA, lipid composition imbalance, and reduced animal longevity on a high-fat diet. The EFA and longevity phenotypes are ameliorated by a reduction of the lipid-droplet-resident protein PLIN2. We show that HDAC6 is associated physically with the chaperone protein dHsc4/Hsc70 to maintain the proteostasis of PLIN2. These findings indicate that proteostasis collapse serves as an intrinsic cue to cause age-dependent EFA. Our study suggests that manipulation of proteostasis could be an alternative approach to the treatment of age-related metabolic diseases such as obesity and diabetes.
巻・号 43(1)
ページ 99-111.e5
公開日 2017-10-9
DOI 10.1016/j.devcel.2017.09.001
PII S1534-5807(17)30714-1
PMID 28966044
MeSH Aging Animals Autophagy / physiology Cytosol / metabolism Diet, High-Fat Drosophila Proteins / metabolism* Drosophila melanogaster / genetics Drosophila melanogaster / metabolism* Fats / metabolism* Histone Deacetylase 6 Histone Deacetylases / metabolism* Lipid Droplets / metabolism* Longevity / physiology Perilipin-2 / metabolism*
IF 9.19
引用数 10
リソース情報
ショウジョウバエ DGRC#105013