A novel brown adipocyte-enriched long non-coding RNA that is required for brown adipocyte differentiation and sufficient to drive thermogenic gene program in white adipocytes |
| |
Authors: | Yan Xiong Feng Yue Zhihao Jia Yun Gao Wen Jin Keping Hu Yong Zhang Dahai Zhu Gongshe Yang Shihuan Kuang |
| |
Affiliation: | 1. Laboratory of Animal Fat Deposition and Muscle Development, College of Animal Science and Technology, Northwest A&F University, Yangling 712100, China;2. Department of Animal Sciences, Purdue University, West Lafayette, IN 47907, USA;3. Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences, Beijing 100193, China;4. The State Key Laboratory of Medical Molecular Biology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences, Department of Biochemistry and Molecular Biology, School of Basic Medicine, Peking Union Medical College, 5 Dong Dan San Tiao, Beijing 100005, China |
| |
Abstract: | The thermogenic activities of brown and beige adipocytes can be exploited to reduce energy surplus and counteract obesity. Recent RNA sequencing studies have uncovered a number of long noncoding RNAs (lncRNAs) uniquely expressed in white and brown adipose tissues (WAT and BAT), but whether and how these lncRNAs function in adipogenesis remain largely unknown. Here, we report the identification of a novel brown adipocyte-enriched LncRNA (AK079912), and its nuclear localization, function and regulation. The expression of AK079912 increases during brown preadipocyte differentiation and in response to cold-stimulated browning of white adipocytes. Knockdown of AK079912 inhibits brown preadipocyte differentiation, manifested by reductions in lipid accumulation and down-regulation of adipogenic and BAT-specific genes. Conversely, ectopic expression of AK079912 in white preadipocytes up-regulates the expression of genes involved in thermogenesis. Mechanistically, inhibition of AK079912 reduces mitochondrial copy number and protein levels of mitochondria electron transport chain (ETC) complexes, whereas AK079912 overexpression increases the levels of ETC proteins. Lastly, reporter and pharmacological assays identify Pparγ as an upstream regulator of AK079912. These results provide new insights into the function of non-coding RNAs in brown adipogenesis and regulating browning of white adipocytes. |
| |
Keywords: | BAT brown adipose tissue WAT white adipose tissue ETC electron transport chain Ucp1 uncoupling protein 1 Cebpα/β/δ CCAAT/enhancer-binding proteins α/β/δ Pparγ peroxisome proliferator-activated receptor gamma Pgc1α Pparγ coactivator 1α Prdm16 PR domain containing 16 miRNAs microRNAs UTR untranslated region Rbp RNA-binding protein Blnc1 brown fat lncRNA 1 Ebf2 early B-cell factor 2 lnc-BATE1 BAT-enriched LncRNA1 hnRNPU nuclear ribonucleoprotein U SVF stromal vascular fraction Lpl lipoprotein lipase Hsl hormone-sensitive lipase Atgl adipose triglyceride lipase Dio2 Type II iodothyronine deiodinase LncRNA AK079912 Brown adipocyte Browning Adipogenesis Pparγ |
本文献已被 ScienceDirect 等数据库收录! |
|