Abstract
Brown adipose tissue (BAT) can convert fatty acids and glucose into heat, exhibiting the potential to combat obesity and diabetes. The mass and activity of BAT gradually diminishes with aging. As a newly found regulator of gene expression, long non-coding RNAs (lncRNAs) exhibit a wide range of functions in life processes. However, whether long non-coding RNA (lncRNA) involves in BAT dysfunction with aging is still unclear. Here, using RNA-sequencing technology, we identified 3237 messenger RNAs (mRNAs) and 1312 lncRNAs as differentially expressed in BAT of 10-months-old mice compared with 6- to 8-week-old. The protein-protein interaction network and k-score analysis revealed that the core mRNAs were associated with two important aging-related pathways, including cell cycle and p53 signaling pathway. Gene set enrichment analysis indicated that these mRNAs might participate in lipid metabolism and brown fat dysfunction. Functional enrichment analyses demonstrated that dysregulated lncRNAs were associated with mitochondria, regulation of cellular senescence, cell cycle, metabolic and p53 signaling pathways. Moreover, we revealed that two lncRNAs (NONMMUT024512 and n281160) may involve in the regulation of their adjacent gene peroxisome proliferator-activated receptor alpha (Pparα), a thermogenesis regulator. Collectively, these results lay a foundation for extensive studies on the role of lncRNAs in age-related thermogenic degradation.
Highlights
Brown adipose tissue (BAT) is an adaptive thermogenic organ that transforms chemical energy into heat in the presence of cold exposure [1]
All animal experiments were approved by the Nanjing Medical University Committee on Care and Use of Animals, and conducted in conformity with the Guide for the Care and Use of Laboratory Animals published by the U.S National Institutes of Health (NIH Publication number 85–23, revised 1996)
We observed that multilocular brown adipocytes markedly disappeared in older mice
Summary
Brown adipose tissue (BAT) is an adaptive thermogenic organ that transforms chemical energy into heat in the presence of cold exposure [1]. BAT contains abundant mitochondria and is characterized by the enrichment of unique uncoupling protein 1 (UCP1), which is located within the inner mitochondrial membrane and dissolves the mitochondrial proton gradient for heat generation [2]. The content of BAT accounts for only a relatively small proportion of the body, 50 g of active BAT can approximately generate 20% of daily energy consumption [3]. Gene Expression in Dysfunctional BAT demonstrates that the mass of human BAT in adults is inversely proportional to body mass index, obesity and glucose level [5]. These findings indicate the critical role of BAT in human metabolism regulation
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