scholarly journals Multidimensional Single-Nuclei RNA-Seq Reconstruction of Adipose Tissue Reveals Adipocyte Plasticity Underlying Thermogenic Response

Cells ◽  
2021 ◽  
Vol 10 (11) ◽  
pp. 3073
Author(s):  
Carlos Alberto Oliveira de Biagi ◽  
Sarah Santiloni Cury ◽  
Cleidson Pádua Alves ◽  
Nabil Rabhi ◽  
Wilson Araujo Silva ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Metabolic Stress ◽  
Rna Seq ◽  
Sequencing Technology ◽  
Cellular Origin ◽  
Depth Analysis ◽  
Thermogenic Adipocytes ◽  
And Function ◽  
Thermogenic Response

Adipose tissue has been classified based on its morphology and function as white, brown, or beige/brite. It plays an essential role as a regulator of systemic metabolism through paracrine and endocrine signals. Recently, multiple adipocyte subtypes have been revealed using RNA sequencing technology, going beyond simply defined morphology but also by their cellular origin, adaptation to metabolic stress, and plasticity. Here, we performed an in-depth analysis of publicly available single-nuclei RNAseq from adipose tissue and utilized a workflow template to characterize adipocyte plasticity, heterogeneity, and secretome profiles. The reanalyzed dataset led to the identification of different subtypes of adipocytes including three subpopulations of thermogenic adipocytes, and provided a characterization of distinct transcriptional profiles along the adipocyte trajectory under thermogenic challenges. This study provides a useful resource for further investigations regarding mechanisms related to adipocyte plasticity and trans-differentiation.

scholarly journals Multidimensional Single-Nuclei RNA-Seq Reconstruction of Adipose Tissue Reveals Adipocyte Plasticity Underlying Thermogenic Response

2021 ◽  
Author(s):  
Carlos Alberto Oliveira de Biagi ◽  
Sarah Santiloni Cury ◽  
Cleidson de Pádua Alves ◽  
Nabil Rahbi ◽  
Wilson Araujo Silva ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Metabolic Stress ◽  
Cell Types ◽  
Adipose Cell ◽  
Cellular Origin ◽  
Depth Analysis ◽  
Thermogenic Adipocytes ◽  
And Function ◽  
Thermogenic Response

AbstractAdipose tissue has been classified based on its morphology and function as white, brown, or beige / brite. It plays an essential role as a regulator of systemic metabolism through paracrine and endocrine signals. Recently, multiple adipocyte subtypes have been revealed using RNA sequencing technology, going beyond simply defined morphology but by their cellular origin, adaptation to metabolic stress, and plasticity. Here, we performed an in-depth analysis of publicly available single-nuclei RNAseq from adipose tissue and utilized a workflow template to characterize adipocyte plasticity, heterogeneity, and secretome profiles. The reanalyzed dataset led to the identification of different subtypes of adipocytes including three subpopulations of thermogenic adipocytes and provided a characterization of distinct transcriptional profiles along the adipocyte trajectory under thermogenic challenges. This study provides a useful resource for further investigations regarding mechanisms related to adipocyte plasticity and trans-differentiation.HighlightsMultidimensional transcriptome analysis at single-nucleus resolution recovers nuclei of cell types in adipose tissueAdaptative thermogenic response results in 3 distinct mature adipose cell typesSingle-nuclei transcriptomic-based secretome analysis reveals adipose cell-type-specific genesThe in vivo trajectory of adipocyte plasticity for thermogenic response reveals sets of trans-differentiation genes

Functional characterization of human brown adipose tissue metabolism

2020 ◽  
Vol 477 (7) ◽  
pp. 1261-1286 ◽  
Author(s):  
Marie Anne Richard ◽  
Hannah Pallubinsky ◽  
Denis P. Blondin
Keyword(s):  
Adipose Tissue ◽  
Brown Adipose Tissue ◽  
Functional Characterization ◽  
Human Infants ◽  
Positron Emission ◽  
Brown Adipose ◽  
Treatment Of Obesity ◽  
And Function

Brown adipose tissue (BAT) has long been described according to its histological features as a multilocular, lipid-containing tissue, light brown in color, that is also responsive to the cold and found especially in hibernating mammals and human infants. Its presence in both hibernators and human infants, combined with its function as a heat-generating organ, raised many questions about its role in humans. Early characterizations of the tissue in humans focused on its progressive atrophy with age and its apparent importance for cold-exposed workers. However, the use of positron emission tomography (PET) with the glucose tracer [18F]fluorodeoxyglucose ([18F]FDG) made it possible to begin characterizing the possible function of BAT in adult humans, and whether it could play a role in the prevention or treatment of obesity and type 2 diabetes (T2D). This review focuses on the in vivo functional characterization of human BAT, the methodological approaches applied to examine these features and addresses critical gaps that remain in moving the field forward. Specifically, we describe the anatomical and biomolecular features of human BAT, the modalities and applications of non-invasive tools such as PET and magnetic resonance imaging coupled with spectroscopy (MRI/MRS) to study BAT morphology and function in vivo, and finally describe the functional characteristics of human BAT that have only been possible through the development and application of such tools.

scholarly journals Highly parallel direct RNA sequencing on an array of nanopores

2016 ◽  
Author(s):  
Daniel R. Garalde ◽  
Elizabeth A. Snell ◽  
Daniel Jachimowicz ◽  
Andrew J. Heron ◽  
Mark Bruce ◽  
...  
Keyword(s):  
Rna Sequencing ◽  
Reverse Transcription ◽  
Biological Information ◽  
Rna Seq ◽  
Sequencing Technology ◽  
Rna Sequences ◽  
Oxford Nanopore ◽  
The Status ◽  
And Function ◽  
Oxford Nanopore Technologies

AbstractRibonucleic acid sequencing can allow us to monitor the RNAs present in a sample. This enables us to detect the presence and nucleotide sequence of viruses, or to build a picture of how active transcriptional processes are changing – information that is useful for understanding the status and function of a sample. Oxford Nanopore Technologies’ sequencing technology is capable of electronically analysing a sample’s DNA directly, and in real-time. In this manuscript we demonstrate the ability of an array of nanopores to sequence RNA directly, and we apply it to a range of biological situations. Nanopore technology is the only available sequencing technology that can sequence RNA directly, rather than depending on reverse transcription and PCR. There are several potential advantages of this approach over other RNA-seq strategies, including the absence of amplification and reverse transcription biases, the ability to detect nucleotide analogues and the ability to generate full-length, strand-specific RNA sequences. Direct RNA sequencing is a completely new way of analysing the sequence of RNA samples and it will improve the ease and speed of RNA analysis, while yielding richer biological information.

scholarly journals Unique transcriptomic signature of omental adipose tissue in Ossabaw swine: a model of childhood obesity

2014 ◽  
Vol 46 (10) ◽  
pp. 362-375 ◽  
Author(s):  
Ryan G. Toedebusch ◽  
Michael D. Roberts ◽  
Kevin D. Wells ◽  
Joseph M. Company ◽  
Kayla M. Kanosky ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Childhood Obesity ◽  
Caloric Intake ◽  
Rna Seq ◽  
Omental Adipose Tissue ◽  
Body Fat Content ◽  
Transcriptomic Signature ◽  
And Function ◽  
Visceral Adipose ◽  
The Impact

To better understand the impact of childhood obesity on intra-abdominal adipose tissue phenotype, a complete transcriptomic analysis using deep RNA-sequencing (RNA-seq) was performed on omental adipose tissue (OMAT) obtained from lean and Western diet-induced obese juvenile Ossabaw swine. Obese animals had 88% greater body mass, 49% greater body fat content, and a 60% increase in OMAT adipocyte area (all P < 0.05) compared with lean pigs. RNA-seq revealed a 37% increase in the total transcript number in the OMAT of obese pigs. Ingenuity Pathway Analysis showed transcripts in obese OMAT were primarily enriched in the following categories: 1) development, 2) cellular function and maintenance, and 3) connective tissue development and function, while transcripts associated with RNA posttranslational modification, lipid metabolism, and small molecule biochemistry were reduced. DAVID and Gene Ontology analyses showed that many of the classically recognized gene pathways associated with adipose tissue dysfunction in obese adults including hypoxia, inflammation, angiogenesis were not altered in OMAT in our model. The current study indicates that obesity in juvenile Ossabaw swine is characterized by increases in overall OMAT transcript number and provides novel data describing early transcriptomic alterations that occur in response to excess caloric intake in visceral adipose tissue in a pig model of childhood obesity.

3308The critical roles of coagulation factors in inducing brown adipose tissue dysfunction and systemic metabolic disorder in obesity

2019 ◽  
Vol 40 (Supplement_1) ◽  
Author(s):  
Y Hayashi ◽  
I S Shimizu ◽  
Y Y Yoshida ◽  
R I Ikegami ◽  
G K Katsuumi ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Membrane Potential ◽  
Glucose Intolerance ◽  
Metabolic Disorder ◽  
Metabolic Disorders ◽  
Metabolic Stress ◽  
Coagulation Factor ◽  
Brown Adipose ◽  
Thermogenic Response

Abstract Obese individuals are predisposed to cardio-metabolic disorders. Brown adipose tissue (BAT) is an active metabolic organ abundant with mitochondria, and studies suggest a potential role of BAT in the maintenance of metabolic health in rodents and humans. Metabolic stress causes BAT dysfunction, but the underlying mechanisms are largely unknown. Coagulation factor Xa (FXa) is critically involved in a coagulation cascade, and it is also known to mediate biological effects by the activation of protease-activated receptor (PAR)-signaling. Accumulating evidence shows that PAR1 contributes to tissue remodeling in cardiovascular system. Here we show a previously unknown role of FXa-PAR signaling in promoting BAT dysfunction and systemic metabolic disorder in a murine dietary obese model. Imposing a high fat diet (HFD) on C57BL/6NCr mice led to a marked increase in tissue factor (TF), coagulation factor VII and FXa in BAT. TF-FVIIa (activated form of FVII)-FXa complex is known to activate PAR1, and we found a significant increase in PAR1 expression in BAT upon metabolic stress. Administration of a FXa inhibitor ameliorated BAT whitening, improved thermogenic response and systemic glucose intolerance upon dietary obesity. In contrast, administration of warfarin did not show any phenotype in BAT. BAT specific TF and PAR1 over-expression model showed significant whitening of this tissue, which was associated with systemic glucose intolerance. BAT specific PAR1 KO mice improved glucose intolerance and thermogenic response under a metabolically stressed condition. In differentiated brown adipocytes, FXa markedly increased mitochondrial reactive oxygen species (ROS) and reduced mitochondrial membrane potential. Inhibition of PAR1 ameliorated FXa-induced mitochondrial ROS production and reduction in membrane potential. We also found that plasma FXa level did not increase in obese mice as well as in obese individuals. These results suggest the previously unknown role of coagulation systems in promoting BAT dysfunction, leading to systemic metabolic disorders. Maintenance of BAT homeostasis through the suppression of FXa-PAR1 signaling would become a new therapeutic target for obesity and diabetes.

scholarly journals The CCR4–NOT Deadenylase Complex Maintains Adipocyte Identity

2019 ◽  
Vol 20 (21) ◽  
pp. 5274 ◽  
Author(s):  
Akinori Takahashi ◽  
Shohei Takaoka ◽  
Shungo Kobori ◽  
Tomokazu Yamaguchi ◽  
Sara Ferwati ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Gene Expression Analysis ◽  
Rna Seq ◽  
Normal Body Temperature ◽  
Metabolic Genes ◽  
Brown Adipose ◽  
Specific Mrnas ◽  
Tissue Characteristics ◽  
And Function

Shortening of poly(A) tails triggers mRNA degradation; hence, mRNA deadenylation regulates many biological events. In the present study, we generated mice lacking the Cnot1 gene, which encodes an essential scaffold subunit of the CCR4–NOT deadenylase complex in adipose tissues (Cnot1-AKO mice) and we examined the role of CCR4–NOT in adipocyte function. Cnot1-AKO mice showed reduced masses of white adipose tissue (WAT) and brown adipose tissue (BAT), indicating abnormal organization and function of those tissues. Indeed, Cnot1-AKO mice showed hyperinsulinemia, hyperglycemia, insulin resistance, and glucose intolerance and they could not maintain a normal body temperature during cold exposure. Muscle-like fibrous material appeared in both WAT and BAT of Cnot1-AKO mice, suggesting the acquisition of non-adipose tissue characteristics. Gene expression analysis using RNA-sequencing (RNA-seq) showed that the levels of adipose tissue-related mRNAs, including those of metabolic genes, decreased, whereas the levels of inflammatory response-related mRNAs increased. These data suggest that the CCR4–NOT complex ensures proper adipose tissue function by maintaining adipocyte-specific mRNAs at appropriate levels and by simultaneously suppressing mRNAs that would impair adipocyte function if overexpressed.

A compendium of G-protein–coupled receptors and cyclic nucleotide regulation of adipose tissue metabolism and energy expenditure

2020 ◽  
Vol 134 (5) ◽  
pp. 473-512 ◽  
Author(s):  
Ryan P. Ceddia ◽  
Sheila Collins
Keyword(s):  
Adipose Tissue ◽  
Energy Expenditure ◽  
Signaling Pathways ◽  
G Protein ◽  
Uncoupling Protein ◽  
Beige Adipocytes ◽  
Nucleotide Regulation ◽  
Ucp1 Expression ◽  
Thermogenic Adipocytes ◽  
G Protein Coupled

Abstract With the ever-increasing burden of obesity and Type 2 diabetes, it is generally acknowledged that there remains a need for developing new therapeutics. One potential mechanism to combat obesity is to raise energy expenditure via increasing the amount of uncoupled respiration from the mitochondria-rich brown and beige adipocytes. With the recent appreciation of thermogenic adipocytes in humans, much effort is being made to elucidate the signaling pathways that regulate the browning of adipose tissue. In this review, we focus on the ligand–receptor signaling pathways that influence the cyclic nucleotides, cAMP and cGMP, in adipocytes. We chose to focus on G-protein–coupled receptor (GPCR), guanylyl cyclase and phosphodiesterase regulation of adipocytes because they are the targets of a large proportion of all currently available therapeutics. Furthermore, there is a large overlap in their signaling pathways, as signaling events that raise cAMP or cGMP generally increase adipocyte lipolysis and cause changes that are commonly referred to as browning: increasing mitochondrial biogenesis, uncoupling protein 1 (UCP1) expression and respiration.

Parasite defense mechanisms in bees: behavior, immunity, antimicrobials, and symbionts

2019 ◽  
Vol 4 (1) ◽  
pp. 59-76 ◽  
Author(s):  
Alison E. Fowler ◽  
Rebecca E. Irwin ◽  
Lynn S. Adler
Keyword(s):  
Defense Mechanisms ◽  
Poor Quality ◽  
Future Research ◽  
Immune Priming ◽  
Social Bees ◽  
Bee Health ◽  
Landscape Scales ◽  
And Function ◽  
Solitary Species

Parasites are linked to the decline of some bee populations; thus, understanding defense mechanisms has important implications for bee health. Recent advances have improved our understanding of factors mediating bee health ranging from molecular to landscape scales, but often as disparate literatures. Here, we bring together these fields and summarize our current understanding of bee defense mechanisms including immunity, immunization, and transgenerational immune priming in social and solitary species. Additionally, the characterization of microbial diversity and function in some bee taxa has shed light on the importance of microbes for bee health, but we lack information that links microbial communities to parasite infection in most bee species. Studies are beginning to identify how bee defense mechanisms are affected by stressors such as poor-quality diets and pesticides, but further research on this topic is needed. We discuss how integrating research on host traits, microbial partners, and nutrition, as well as improving our knowledge base on wild and semi-social bees, will help inform future research, conservation efforts, and management.

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