scholarly journals Regulatory networks of non-coding RNAs in brown/beige adipogenesis

2015 ◽  
Vol 35 (5) ◽  
Author(s):  
Shaohai Xu ◽  
Peng Chen ◽  
Lei Sun

BAT (brown adipose tissue) is specialized to burn fatty acids for heat generation and energy expenditure to defend against cold and obesity. Accumulating studies have demonstrated that manipulation of BAT activity through various strategies can regulate metabolic homoeostasis and lead to a healthy phenotype. Two classes of ncRNA (non-coding RNA), miRNA and lncRNA (long non-coding RNA), play crucial roles in gene regulation during tissue development and remodelling. In the present review, we summarize recent findings on regulatory role of distinct ncRNAs in brown/beige adipocytes, and discuss how these ncRNA regulatory networks contribute to brown/beige fat development, differentiation and function. We suggest that targeting ncRNAs could be an attractive approach to enhance BAT activity for protecting the body against obesity and its pathological consequences.

2017 ◽  
Vol 86 (3) ◽  
pp. 227
Author(s):  
Aleksander Rajczewski ◽  
Magdalena Gibas-Dorna

This review discusses the effects of glucocorticoids (GCs) on brown adipose tissue (BAT) in the context of obesity prevention and therapy. Due to the unique expression of the uncoupling protein 1 (UCP1), BAT is capable of non‑shivering thermogenesis, also defined as a metabolic heat production, related to increased metabolic rate. All processes that contribute to an increase in activity and/or quantity of BAT are able to upturn metabolism, and thus enable the above therapeutic goals to be achieved. GCs may stimulate BAT differentiation and proliferation. In the case of differentiation, the opposite effect of GCs has been also described. Within white adipose tissue (WAT) GCs inhibit the formation of so called beige adipocytes that are functionally and morphologically similar to the adipocytes from BAT. The activity of GCs with concomitant inhibition of WAT browning is mediated by the induction of microRNA-27b (MIR27B) expression. GCs are responsible for the decline in BAT activity as the body ages. Depriving the body of an enzyme responsible for local reduction of cortisone into an active GC‑cortisol in BAT (11β‑hydroxysteroid dehydrogenase type 1; 11β‑HSD1) prevents the reduction of BAT activity. The effects of high doses of GCs on BAT generally depend on the exposure time. Prolonged elevation in GCs level decreases BAT activity. During adrenergic stimulation the effect of GCs on BAT is ambiguous, because both decrease and increase in activity has been described. A full understanding of the GCs impact on brown remodeling in WAT may reveal a discovery of a novel preventive and therapeutic strategies for obesity and possibly other metabolic disorders.


2021 ◽  
pp. 10-18
Author(s):  
Irina Chernukha ◽  
Liliya Fedulova ◽  
Elena Kotenkova

Introduction. Traditionally, mammalian adipose tissue is divided into white (white adipose tissue – WAT) and brown (brown adipose tissue – BAT). While the functions of WAT are well known as the triglyceride depot, the role of BAT in mammalian physiology has been under close investigation. The first description of the role of BAT in maintaining thermogenesis dates back to 1961. This article offers a review of structural and functional specificity of white, beige and brown adipose tissue. Results and discussion. The differences and descriptions of adipocytes and their impact on the maintenance of the main functions of the mammalian body are described in this manuscript. In particular, thermogenesis, stress response, obesity, type II diabetes. In addition to WAT and BAT, an intermediate form was also detected in the body – beige fat (BeAT or Brite). The opposite opinions regarding the presence of three types of adipose tissue in the human and animal bodies are presented. Studies on the identification of uncoupling proteins 1 and 3 and their role in the transformation of white fat into beige/brown are considered. Basically, the data on the factors of endogenous and exogenous nature on their formation are given on the example of the human body. Conclusion. With an abundance of publications on the keywords: “white, brown fat”, these studies, in the overwhelming majority, are devoted to the role of these fats in the formation of human thermogenesis, the assessment of the impact on obesity. Pigs have also been suggested to lack functional BAT, which is a major cause of neonatal death in the swine industry, therefore the focus on investigating role of different types of adipose tissue in pigs seems very promising in order to understand whether there is a compensating mechanism of thermogenesis.


2021 ◽  
Vol 27 (1) ◽  
Author(s):  
Senxiang Chen ◽  
Da Liu ◽  
Zimo Zhou ◽  
Sen Qin

Abstract Background Osteoporosis is a widespread and serious metabolic bone disease. At present, revealing the molecular mechanisms of osteoporosis and developing effective prevention and treatment methods are of great significance to health worldwide. LncRNA is a non-coding RNA peptide chain with more than 200 nucleotides. Researchers have identified many lncRNAs implicated in the development of diseases and lncRNA H19 is an example. Results A large amount of evidence supports the fact that long non-coding RNA (lncRNA) genes, such as H19, have multiple, far-reaching effects on various biological functions. It has been found that lncRNA H19 has a role in the regulation of different types of cells in the body including the osteoblasts, osteocytes, and osteoclasts found in bones. Therefore, it can be postulated that lncRNA H19 affects the incidence and development of osteoporosis. Conclusion The prospect of targeting lncRNA H19 in the treatment of osteoporosis is promising because of the effects that lncRNA H19 has on the process of osteogenic differentiation. In this review, we summarize the molecular pathways and mechanisms of lncRNA H19 in the pathogenesis of osteoporosis and summarize the research progress of targeting H19 as a treatment option. Research is emerging that explores more effective treatment possibilities for bone metabolism diseases using molecular targets.


2020 ◽  
Vol 65 (3) ◽  
pp. 97-107
Author(s):  
Yuanyuan Huang ◽  
Hanlin Zhang ◽  
Meng Dong ◽  
Lei Zhang ◽  
Jun Lin ◽  
...  

White adipose tissue (WAT) browning may have beneficial effects for treating metabolic syndrome. miRNA are important regulators of the differentiation, development, and function of brown and beige adipocytes. Here, we found that the cold-inducible miRNA17-92 cluster is enriched in brown adipose tissue (BAT) compared with WAT. Overexpression of the miR17-92 cluster in C3H10T1/2 cells, a mouse mesenchymal stem cell line, enhanced the thermogenic capacity of adipocytes. Furthermore, we observed a significant reduction in adiposity in adipose tissue-specific miR17-92 cluster transgenic (TG) mice. This finding is partly explained by dramatic increases in white fat browning and energy expenditure. Interestingly, the miR17-92 cluster stimulated WAT browning without altering BAT activity in mice. In addition, when we removed the intrascapular BAT (iBAT), the TG mice could maintain their body temperature well under cold exposure. At the molecular level, we found that the miR17-92 cluster targets Rb1, a beige cell repressor in WAT. The present study reveals a critical role for the miR17-92 cluster in regulating WAT browning. These results may be helpful for better understanding the function of beige fat, which could compensate for the lack of BAT in humans, and may open new avenues for combatting metabolic syndrome.


2022 ◽  
Vol 12 ◽  
Author(s):  
Malik Bisserier ◽  
Nathaniel Saffran ◽  
Agnieszka Brojakowska ◽  
Aimy Sebastian ◽  
Angela Clare Evans ◽  
...  

During spaceflight, astronauts are exposed to multiple unique environmental factors, particularly microgravity and ionizing radiation, that can cause a range of harmful health consequences. Over the past decades, increasing evidence demonstrates that the space environment can induce changes in gene expression and RNA processing. Long non-coding RNA (lncRNA) represent an emerging area of focus in molecular biology as they modulate chromatin structure and function, the transcription of neighboring genes, and affect RNA splicing, stability, and translation. They have been implicated in cancer development and associated with diverse cardiovascular conditions and associated risk factors. However, their role on astronauts’ health after spaceflight remains poorly understood. In this perspective article, we provide new insights into the potential role of exosomal lncRNA after spaceflight. We analyzed the transcriptional profile of exosomes isolated from peripheral blood plasma of three astronauts who flew on various Shuttle missions between 1998–2001 by RNA-sequencing. Computational analysis of the transcriptome of these exosomes identified 27 differentially expressed lncRNAs with a Log2 fold change, with molecular, cellular, and clinical implications.


Author(s):  
Eric A J Simko ◽  
Honghe Liu ◽  
Tao Zhang ◽  
Adan Velasquez ◽  
Shraddha Teli ◽  
...  

Abstract The long non-coding RNA NEAT1 serves as a scaffold for the assembly of paraspeckles, membraneless nuclear organelles involved in gene regulation. Paraspeckle assembly requires NEAT1 recruitment of the RNA-binding protein NONO, however the NEAT1 elements responsible for recruitment are unknown. Herein we present evidence that previously unrecognized structural features of NEAT1 serve an important role in these interactions. Led by the initial observation that NONO preferentially binds the G-quadruplex conformation of G-rich C9orf72 repeat RNA, we find that G-quadruplex motifs are abundant and conserved features of NEAT1. Furthermore, we determine that NONO binds NEAT1 G-quadruplexes with structural specificity and provide evidence that G-quadruplex motifs mediate NONO-NEAT1 association, with NONO binding sites on NEAT1 corresponding largely to G-quadruplex motifs, and treatment with a G-quadruplex-disrupting small molecule causing dissociation of native NONO-NEAT1 complexes. Together, these findings position G-quadruplexes as a primary candidate for the NONO-recruiting elements of NEAT1 and provide a framework for further investigation into the role of G-quadruplexes in paraspeckle formation and function.


2015 ◽  
Vol 37 (2) ◽  
pp. 14-18 ◽  
Author(s):  
Adrian Whitehouse

More than 100 different types of chemical modifications are found in cellular RNAs, including ribosomal RNA (rRNA), transfer RNA (tRNA), messenger RNA (mRNA), long non-coding RNA (lncRNA) and small nuclear RNA (snRNA). Internal modifications of mRNA were first observed in the 1970s, but, until recently, the role of these mRNA modifications has been a largely neglected field. A long-standing view was that mRNA modifications were static and unalterable, having a minor role in fine-tuning the structure and function of mRNAs. However, recent exciting discoveries now suggest that certain mRNA modifications are dynamic and, in some cases, reversible. Therefore they may have critical regulatory roles in gene expression, analogous to those which dynamically regulate DNA and protein modifications. As such, understanding the scope and mechanisms of these dynamic mRNA modifications represents an emerging layer of gene regulation at the RNA level, termed epitranscriptomics or RNA epigenetics.


2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Liting You ◽  
Qian Wu ◽  
Zhaodan Xin ◽  
Huiyu Zhong ◽  
Juan Zhou ◽  
...  

Abstract Background miR-124-3p can inhibit integrin β3 (ITGB3) expression to suppress the migration and invasion of gastric cancer (GC), and in the process lncRNA HOXA11-AS may act as a molecular sponge. Methods Luciferase reporter assay was conducted to verify the binding of miR-124-3p and HOXA11-AS. RT-PCR and western blot were performed to detect the expression of HOXA11-AS, miR-124-3p and ITGB3 in GC tissues and cells. Gene silence and overexpression experiments as well as cell migration and invasion assays on GC cell lines were performed to determine the regulation of molecular pathways, HOXA11-AS/miR-124-3p/ITGB3. Furthermore, the role of HOXA11-AS in GC was confirmed in mice models. Results We found HOXA11-AS is up-regulated in GC tissues and can bind with miR-124-3p. Through overexpression/knockdown experiments and function tests in vitro, we demonstrated HOXA11-AS can promote ITGB3 expression by sponging miR-124-3p, consequently enhance the proliferation, migration, and invasion of GC cells. Meanwhile, we validated that HOXA11-AS promotes migration and invasion of GC cells via down-regulating miR-124-3p and up-regulating ITGB3 in vivo. Conclusions We demonstrated that lncRNA HOXA11-AS can increase ITGB3 expression to promote the migration and invasion of gastric cancer by sponging miR-124-3p. Our results suggested that HOXA11-AS may reasonably serve as a promising diagnostic biomarker and a potential therapeutic target of GC.


2021 ◽  
Vol 11 (6) ◽  
pp. 513
Author(s):  
Zheng Zhang ◽  
Meng Gu ◽  
Zhongze Gu ◽  
Yan-Ru Lou

Genetic polymorphisms are defined as the presence of two or more different alleles in the same locus, with a frequency higher than 1% in the population. Since the discovery of long non-coding RNAs (lncRNAs), which refer to a non-coding RNA with a length of more than 200 nucleotides, their biological roles have been increasingly revealed in recent years. They regulate many cellular processes, from pluripotency to cancer. Interestingly, abnormal expression or dysfunction of lncRNAs is closely related to the occurrence of human diseases, including cancer and degenerative neurological diseases. Particularly, their polymorphisms have been found to be associated with altered drug response and/or drug toxicity in cancer treatment. However, molecular mechanisms are not yet fully elucidated, which are expected to be discovered by detailed studies of RNA–protein, RNA–DNA, and RNA–lipid interactions. In conclusion, lncRNAs polymorphisms may become biomarkers for predicting the response to chemotherapy in cancer patients. Here we review and discuss how gene polymorphisms of lncRNAs affect cancer chemotherapeutic response. This knowledge may pave the way to personalized oncology treatments.


2021 ◽  
Vol 16 (1) ◽  
pp. 1-13
Author(s):  
Weiwei Liu ◽  
Dongmei Yao ◽  
Bo Huang

Abstract Cervical cancer (CC) is a huge threat to the health of women worldwide. Long non-coding RNA plasmacytoma variant translocation 1 gene (PVT1) was proved to be associated with the development of diverse human cancers, including CC. Nevertheless, the exact mechanism of PVT1 in CC progression remains unclear. Levels of PVT1, microRNA-503 (miR-503), and ADP ribosylation factor-like protein 2 (ARL2) were measured by quantitative reverse transcription-polymerase chain reaction or western blot assay. 3-(4,5)-Dimethylthiazole-2-y1)-2,5-biphenyl tetrazolium bromide (MTT) and flow cytometry were used to examine cell viability and apoptosis, respectively. For migration and invasion detection, transwell assay was performed. The interaction between miR-503 and PVT1 or ARL2 was shown by dual luciferase reporter assay. A nude mouse model was constructed to clarify the role of PVT1 in vivo. PVT1 and ARL2 expressions were increased, whereas miR-503 expression was decreased in CC tissues and cells. PVT1 was a sponge of miR-503, and miR-503 targeted ARL2. PVT1 knockdown suppressed proliferation, migration, and invasion of CC cells, which could be largely reverted by miR-503 inhibitor. In addition, upregulated ARL2 could attenuate si-PVT1-mediated anti-proliferation and anti-metastasis effects on CC cells. Silenced PVT1 also inhibited CC tumor growth in vivo. PVT1 knockdown exerted tumor suppressor role in CC progression via the miR-503/ARL2 axis, at least in part.


Sign in / Sign up

Export Citation Format

Share Document