scholarly journals A long-non-coding RNA, LINC00473, confers the human adipose tissue thermogenic phenotype through enhanced cAMP responsiveness

2018 ◽  
Author(s):  
Khanh-Van Tran ◽  
Cecilie Nandrup-Bus ◽  
Tiffany DeSouza ◽  
Ricardo Soares ◽  
Naja Zenius Jespersen ◽  
...  
Keyword(s):  
Metabolic Disease ◽  
Adipose Tissue ◽  
Disease Risk ◽  
Human Adipose Tissue ◽  
Non Coding Rna ◽  
Highly Correlated ◽  
Thermogenic Adipocytes ◽  
The Many ◽  
External Stimuli ◽  
Long Non Coding Rna

SummarySpecialized adipocytes localized in distinct depots mediate the many physiological functions of adipose tissue. In humans, paucity of thermogenic adipocytes correlates with high metabolic disease risk, raising much interest in the mechanisms by which these cells arise. Here we report molecular signatures associated with adipocyte development in different human depots and identify a long non-coding RNA, LINC00473, as the transcript most closely associated with enrichment of thermogenic adipocytes. LINC00473 expression is low in subjects with obesity or type-2 diabetes and is highly correlated with cAMP signaling and mitochondrial oxidative phosphorylation pathways. LINC00473 is localized in the nucleus and the cytoplasm, and its knockdown impairs induction of UCP1 and mitochondrial respiration. These results reveal that depot-enriched genes that modulate responsiveness to external stimuli, specifically LINC00473, are important determinants of the adipose tissue thermogenic phenotype, and potential targets for metabolic disease therapy.

“Multiple human adipocyte subtypes and mechanisms of their development”

2019 ◽  
Author(s):  
So Yun Min ◽  
Anand Desai ◽  
Zinger Yang ◽  
Agastya Sharma ◽  
Ryan M.J. Genga ◽  
...  
Keyword(s):  
Metabolic Disease ◽  
Adipose Tissue ◽  
Disease Risk ◽  
Human Adipose Tissue ◽  
Transcriptional Repressors ◽  
Mesenchymal Progenitor Cells ◽  
Human Adipocyte ◽  
Adipose Tissue Depots ◽  
Beige Adipocytes ◽  
Low Levels

SUMMARYHuman adipose tissue depots perform numerous diverse physiological functions, and are differentially linked to metabolic disease risk, yet only two major human adipocyte subtypes have been described, white and “brown/brite/beige.” The diversity and lineages of adipocyte classes have been studied in mice using genetic methods that cannot be applied in humans. Here we circumvent this problem by studying the fate of single mesenchymal progenitor cells obtained from human adipose tissue. We report that a minimum of four human adipocyte subtypes can be distinguished by transcriptomic analysis, specialized for functionally distinct processes such as adipokine secretion and thermogenesis. Evidence for the presence of these adipocytes subtypes in adult humans is evidenced by differential expression of key adipokines leptin and adiponectin in isolated mature adipocytes. The human adipocytes most similar to the mouse “brite/beige” adipocytes are enriched in mechanisms that promote iron accumulation and protect from oxidative stress, and are derived from progenitors that express high levels of cytokines such as IL1B, IL8, IL11 and the IL6 family cytokine LIF, and low levels of the transcriptional repressors ID1 and ID3. Our finding of this adipocyte repertoire and its developmental mechanisms provides a high-resolution framework to analyze human adipose tissue architecture and its role in systemic metabolism and metabolic disease.

scholarly journals De Novo Reconstruction of Adipose Tissue Transcriptomes Reveals Long Non-coding RNA Regulators of Brown Adipocyte Development

2015 ◽  
Vol 21 (5) ◽  
pp. 764-776 ◽  
Author(s):  
Juan R. Alvarez-Dominguez ◽  
Zhiqiang Bai ◽  
Dan Xu ◽  
Bingbing Yuan ◽  
Kinyui Alice Lo ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
De Novo ◽  
Brown Adipocyte ◽  
Non Coding Rna ◽  
Adipocyte Development ◽  
Long Non Coding Rna

scholarly journals De Novo Reconstruction of Adipose Tissue Transcriptomes Reveals Long Non-coding RNA Regulators of Brown Adipocyte Development

2015 ◽  
Vol 21 (6) ◽  
pp. 918
Author(s):  
Juan R. Alvarez-Dominguez ◽  
Zhiqiang Bai ◽  
Dan Xu ◽  
Bingbing Yuan ◽  
Kinyui Alice Lo ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
De Novo ◽  
Brown Adipocyte ◽  
Non Coding Rna ◽  
Adipocyte Development ◽  
Long Non Coding Rna

scholarly journals Global mRNA and Long Non-Coding RNA Expression in the Placenta and White Adipose Tissue of Mice Fed a High-Fat Diet During Pregnancy

2018 ◽  
Vol 50 (6) ◽  
pp. 2260-2271 ◽  
Author(s):  
Chen Huang ◽  
Bin-bin Huang ◽  
Jian-min Niu ◽  
Yan Yu ◽  
Xiao-yun Qin ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Adipose Tissue ◽  
Gestational Diabetes ◽  
Gestational Diabetes Mellitus ◽  
High Fat Diet ◽  
Differentially Expressed ◽  
High Fat ◽  
The Core ◽  
Non Coding Rna ◽  
Long Non Coding Rna

Background/Aims: Gestational diabetes mellitus (GDM) is a common complication of pregnancy, but the mechanisms underlying the disorders remain unclear. The study aimed to identify mRNA and long non-coding RNA (lncRNA) profiles in placenta and gonadal fat of pregnant mice fed a high-fat diet and to investigate the transcripts and pathways involved in the development of gestational diabetes mellitus. Methods: Deep and broad transcriptome profiling was performed to assess the expression of mRNAs and lncRNAs in placenta and gonadal fat from 3 mice fed an HFD and chow during pregnancy. Then, differentially expressed mRNAs and lncRNAs were validated by quantitative real-time PCR. The function of the differentially expressed mRNAs was determined by pathway and Gene Ontology (GO) analyses, and the physical or functional relationships between the lncRNAs and the corresponding mRNAs were determined. Results: Our study revealed that 82 mRNAs and 52 lncRNAs were differentially expressed in the placenta of mice fed an HFD during pregnancy, and 202 mRNAs and 120 lncRNAs were differentially expressed in gonadal fat. GO and Kyoto Encyclopedia of Genes and Genomes pathway analyses revealed differentially expressed mRNAs of placenta were closely related to extracellular matrix interactions, digestion, adhesion, and metabolism, whereas the differentially expressed mRNAs in adipose tissue were related to metabolic and insulin signalling pathways. The gene network demonstrated that Actg2, Cnfn, Muc16, Serpina3k, NONMMUT068202, and NONMMUT068203, were the core of the network in placental tissue, and the genes Tkt, Acss2, and Elovl6 served as the core of the network in gonadal fat tissue. Conclusion: These newly identified key genes and pathways in mice might provide valuable information regarding the pathogenesis of GDM and might be used to improve early diagnosis, prevention, drug design, and clinical treatment.

Adipocyte heterogeneity underlying adipose tissue functions

Endocrinology ◽  
2021 ◽  
Author(s):  
Zinger Yang Loureiro ◽  
Javier Solivan-Rivera ◽  
Silvia Corvera
Keyword(s):  
Metabolic Disease ◽  
Adipose Tissue ◽  
Tissue Distribution ◽  
Single Cell ◽  
Disease Risk ◽  
Stromal Vascular Fraction ◽  
Transcriptome Profiling ◽  
Complete Characterization ◽  
Relative Mass ◽  
Adipose Tissue Distribution

Abstract Adipose tissue distribution in the human body is highly heterogeneous, and the relative mass of different depots is differentially associated with metabolic disease risk. Distinct functions of adipose depots are mediated by their content of specialized adipocyte subtypes, best exemplified by thermogenic adipocytes found in specific depots. Single-cell transcriptome profiling has been used to define the cellular composition of many tissues and organs, but the large size, buoyancy and fragility of adipocytes have rendered it challenging to apply these techniques to understand the full complexity of adipocyte subtypes in different depots. Discussed here are strategies that have been recently developed for investigating adipocyte heterogeneity, including single-cell RNASeq profiling of the stromal vascular fraction to identify diverse adipocyte progenitors, and single-nuclei profiling to characterize mature adipocytes. These efforts are yielding a more complete characterization of adipocyte subtypes in different depots, insights into the mechanisms of their development, and perturbations associated with different physiological states such as obesity. A better understanding of the adipocyte subtypes that compose different depots will help explain metabolic disease phenotypes associated with adipose tissue distribution and suggest new strategies for improving metabolic health.

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