Adipocyte Long-Noncoding RNA Transcriptome Analysis of Obese Mice Identified <i>Lnc-Leptin</i>, Which Regulates Leptin

Lo, Kinyui Alice; Huang, Shiqi; Walet, Arcinas Camille Esther; Zhang, Zhichun; Leow, Melvin Khee–Shing; Liu, Meihui; Sun, Li

doi:10.2337/db17-0526

Cited by 54 publications

(44 citation statements)

References 47 publications

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“…To explore the role of lncRNAs in adipose tissue during obesity, Lo et al ( 72 ) examined the lncRNA expression changes in BAT, epididymal WAT, and iWAT with RNA-seq and identified a set of lncRNAs regulated in all three depots during obesity and in the fed versus fast state. One of these lncRNAs was located ∼20 kb upstream of Leptin, referred to as lnc-Leptin .…”

Section: Lncrna Regulation Of White Adipocyte Differentiation and Funmentioning

confidence: 99%

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Function and Mechanism of Long Noncoding RNAs in Adipocyte Biology

Sun

Lin

2019

Diabetes

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The last two decades have witnessed an explosion of interest in adipocyte biology, coinciding with the upsurge of obesity and metabolic syndrome. Now we have new perspectives on the distinct developmental origins of white, brown, and beige adipocytes and their role in metabolic physiology and disease. Beyond fuel metabolism, adipocytes communicate with the immune system and other tissues by releasing diverse paracrine and endocrine factors to orchestrate adipose tissue remodeling and maintain systemic homeostasis. Significant progress has been made in delineating the regulatory networks that govern different aspects of adipocyte biology. Here we provide an overview on the emerging role of long noncoding RNAs (lncRNAs) in the regulation of adipocyte development and metabolism and discuss the implications of the RNA–protein regulatory interface in metabolic control.

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Section: Lncrna Regulation Of White Adipocyte Differentiation and Funmentioning

confidence: 99%

“…2 ). Therefore, lnc-Leptin regulates Leptin expression by mediating the formation of enhancer–promoter interaction ( 72 ).…”

Section: Lncrna Regulation Of White Adipocyte Differentiation and Funmentioning

confidence: 99%

Function and Mechanism of Long Noncoding RNAs in Adipocyte Biology

Sun

Lin

2019

Diabetes

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“…Moreover, several studies reported that members of the TGFβ(transforming growth factor β) superfamily hold distinct regulatory effects on brown adipogenesis [34,35]. In addition to the regulation of transcription levels, epigenetic regulation, including microRNA [36], lncRNA [37][38][39][40], and methylation [41,42], also play essential roles in the formation and activation of BAT [43]. Although circRNA has been rarely reported in the regulation of brown adipogenesis and functions, we believe it is also a very promising potential regulator.…”

Section: Introductionmentioning

confidence: 91%

Comprehensive Analysis of the Characteristics and Differences in Adult and Newborn Brown Adipose Tissue (BAT): Newborn BAT Is a More Active/Dynamic BAT

Liu

Zhang

et al. 2020

Cells

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Brown adipose tissue (BAT) plays an essential role in maintaining body temperature and in treating obesity and diabetes. The adult BAT (aBAT) and neonatal BAT (neBAT) vary greatly in capacity, but the characteristics and differences between them on the molecular level, as well as the related features of BAT as it develops post-delivery, have not yet been fully determined. In this study, we examined the morphological features of aBAT and neBAT of mice by using hematoxylin-eosin (H&E) staining, transmission electron microscopy (TEM), and scanning electron microscopy (SEM). We found that neBAT contains a smaller number and size of lipid droplets, as well as more abundant mitochondria, compared with aBAT. The dynamic morphological changes revealed that the number and size of lipid droplets increase, but the number of mitochondria gradually decrease during the post-delivery development, which consisted of some differences in RNA or protein expression levels, such as gradually decreased uncoupling protein 1 (UCP1) expression levels and mitochondrial genes, such as mitochondrial transcription factor A (Tfam). The adipocyte differentiation-related genes, such as transcription factor CCAAT enhancer-binding protein β (CEBPβ), were also continuously upregulated. Additionally, the different features of aBAT and neBAT were analyzed from the global transcription (RNA-Seq) level, which included messenger RNA (mRNA), microRNA, long non-coding RNA (lncRNA), circRNA, and DNA methylation, as well as proteins (proteomics). Differentially methylated region (DMR) analysis identified 383 hyper- and 503 hypo-methylated genes, as well as 1221 new circRNA in ne-BAT and 1991 new circRNA in a-BAT, with significantly higher expression of circRNA in aBAT compared with neBAT. Gene ontology (GO) enrichment analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis indicated that mitochondrial activity, protein synthesis, and cell life activity levels were higher in neBAT, and pathways related to ribosomes, spliceosomes, and metabolism were significantly activated in neBAT compared to aBAT. Collectively, this study describes the dynamic changes occurring throughout post-delivery development from the morphological, molecular and omics perspectives. Our study provides information that may be utilized in improving BAT functional activity through gene regulation and/or epigenetic regulation.

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“…Robust mouse lncRNA metabolic regulators (mLMRs), such as Lexis, Mexis, and Blnc1 [9][10][11] , have also been reported by many groups and this list continues to expand. Furthermore, several genomewide transcriptome analyses in mice have identified hundreds of potential mLMRs in key metabolic organs suggesting that mouse lncRNAs constitute an additional dimension of metabolic regulation 12,13 . If human lncRNAs exercise a similar function, studying their metabolic function could help systemically uncover novel regulatory mechanisms of human metabolism and expand our understanding of how metabolic disease is initiated and progresses.…”

Section: Introductionmentioning

confidence: 99%

Multilevel integrative transcriptome analyses in humans and humanized mice define in vivo human lncRNA metabolic regulators

Ruan

et al. 2020

Preprint

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A growing number of long non-coding RNAs (lncRNAs) have emerged as vital metabolic regulators in research animals suggesting that lncRNAs could also play an important role in human metabolism. However, most human lncRNAs are non-conserved, vastly limiting our ability to identify human lncRNA metabolic regulators (hLMRs). As the sequence-function relation of lncRNAs has yet to be established, the identification of lncRNA metabolic regulators in animals often relies on their regulations by experimental metabolic conditions. But it is very challenging to apply this strategy to human lncRNAs because well-controlled human data are much limited in scope and often confounded by genetic heterogeneity. In this study, we establish an efficient pipeline to identify putative hLMRs that are metabolically sensitive, disease-relevant, and population applicable. We first progressively processed human transcriptome data to select human liver lncRNAs that exhibit highly dynamic expression in the general population, show differential expression in a metabolic disease population, and response to dietary intervention in a small disease cohort. We then experimentally demonstrated the responsiveness of selected hepatic lncRNAs to defined metabolic milieus in a liver-specific humanized mouse model. Furthermore, by extracting a concise list of protein-coding genes that are persistently correlated with lncRNAs in general and metabolic disease populations, we predicted the specific function for each hLMR.Using gain-and loss-of-function approaches in humanized mice as well as ectopic expression in conventional mice, we were able to validate the regulatory role of one non-conserved hLMR in cholesterol metabolism. Mechanistically, this hLMR binds to an RNA-binding protein, PTBP1, to modulate the transcription of cholesterol synthesis genes. In summary, our study provides a pipeline to overcome the variabilities intrinsic to human data to enable the efficient identification and functional definition of hLMRs. The combination of this bioinformatic framework and

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Adipocyte Long-Noncoding RNA Transcriptome Analysis of Obese Mice Identified Lnc-Leptin, Which Regulates Leptin

Cited by 54 publications

References 47 publications

Function and Mechanism of Long Noncoding RNAs in Adipocyte Biology

Function and Mechanism of Long Noncoding RNAs in Adipocyte Biology

Comprehensive Analysis of the Characteristics and Differences in Adult and Newborn Brown Adipose Tissue (BAT): Newborn BAT Is a More Active/Dynamic BAT

Multilevel integrative transcriptome analyses in humans and humanized mice define in vivo human lncRNA metabolic regulators

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