HDAC6 Suppresses Age-Dependent Ectopic Fat Accumulation by Maintaining the Proteostasis of PLIN2 in Drosophila

Publication date: Available online 28 September 2017
Source:Developmental Cell
Author(s): Yan Yan, Hao Wang, Minling Hu, Lifen Jiang, Yang Wang, Pingsheng Liu, Xuehong Liang, Jiyong Liu, Changqing Li, Anya Lindström-Battle, Sin Man Lam, Guanghou Shui, Wu-Min Deng, Renjie Jiao
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.

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Teaser

Age-dependent ectopic fat accumulation (EFA) contributes to the effects of aging and metabolic diseases such as obesity. Yan et al. characterize age-dependent EFA in Drosophila and reveal that the maintenance of proteostasis of lipid droplet protein PLIN2 by proteostatic factors, dHDAC6 and dHsc4, is essential for suppressing age-dependent EFA.


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