scholarly journals mTOR signaling in Brown and Beige adipocytes: implications for thermogenesis and obesity

2019 ◽  
Vol 16 (1) ◽  
Author(s):  
Yuqing Ye ◽  
Hailan Liu ◽  
Feng Zhang ◽  
Fang Hu
Keyword(s):  
Energy Metabolism ◽  
Animal Models ◽  
Signaling Pathways ◽  
Heat Production ◽  
Regulatory Networks ◽  
Nonshivering Thermogenesis ◽  
Mechanistic Target Of Rapamycin ◽  
Experimental Systems ◽  
Beige Adipocytes ◽  
Distinct Features

Abstract Brown and beige adipocytes are mainly responsible for nonshivering thermogenesis or heat production, despite the fact that they have distinguished features in distribution, developmental origin, and functional activation. As a nutrient sensor and critical regulator of energy metabolism, mechanistic target of rapamycin (mTOR) also plays an important role in the development and functional maintenance of adipocytes. While the recent studies support the notion that mTOR (mTORC1 and mTORC2) related signaling pathways are of great significance for thermogenesis and the development of brown and beige adipocytes, the exact roles of mTOR in heat production are controversial. The similarities and disparities in terms of thermogenesis might be ascribed to the use of different animal models and experimental systems, distinct features of brown and beige adipocytes, and the complexity of regulatory networks of mTORC1 and mTORC2 in energy metabolism.

scholarly journals Mitochondria in White, Brown, and Beige Adipocytes

2016 ◽  
Vol 2016 ◽  
pp. 1-11 ◽  
Author(s):  
Miroslava Cedikova ◽  
Michaela Kripnerová ◽  
Jana Dvorakova ◽  
Pavel Pitule ◽  
Martina Grundmanova ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Adipose Tissue ◽  
Energy Metabolism ◽  
Oxygen Radicals ◽  
Adipocyte Differentiation ◽  
Nonshivering Thermogenesis ◽  
Adipose Tissues ◽  
White Adipocytes ◽  
Beige Adipocytes ◽  
Colour Appearance

Mitochondria play a key role in energy metabolism in many tissues, including cardiac and skeletal muscle, brain, liver, and adipose tissue. Three types of adipose depots can be identified in mammals, commonly classified according to their colour appearance: the white (WAT), the brown (BAT), and the beige/brite/brown-like (bAT) adipose tissues. WAT is mainly involved in the storage and mobilization of energy and BAT is predominantly responsible for nonshivering thermogenesis. Recent data suggest that adipocyte mitochondria might play an important role in the development of obesity through defects in mitochondrial lipogenesis and lipolysis, regulation of adipocyte differentiation, apoptosis, production of oxygen radicals, efficiency of oxidative phosphorylation, and regulation of conversion of white adipocytes into brown-like adipocytes. This review summarizes the main characteristics of each adipose tissue subtype and describes morphological and functional modifications focusing on mitochondria and their activity in healthy and unhealthy adipocytes.

scholarly journals Zbtb7b engages the long noncoding RNA Blnc1 to drive brown and beige fat development and thermogenesis

2017 ◽  
Vol 114 (34) ◽  
pp. E7111-E7120 ◽  
Author(s):  
Siming Li ◽  
Lin Mi ◽  
Lei Yu ◽  
Qi Yu ◽  
Tongyu Liu ◽  
...  
Keyword(s):  
Energy Metabolism ◽  
Long Noncoding Rna ◽  
Noncoding Rna ◽  
Regulatory Networks ◽  
Gene Activation ◽  
Brown Fat ◽  
Genetic Ablation ◽  
A Genome ◽  
Beige Adipocytes ◽  
Beige Fat

Brown and beige adipocytes convert chemical energy into heat through uncoupled respiration to defend against cold stress. Beyond thermogenesis, brown and beige fats engage other metabolic tissues via secreted factors to influence systemic energy metabolism. How the protein and long noncoding RNA (lncRNA) regulatory networks act in concert to regulate key aspects of thermogenic adipocyte biology remains largely unknown. Here we developed a genome-wide functional screen to interrogate the transcription factors and cofactors in thermogenic gene activation and identified zinc finger and BTB domain-containing 7b (Zbtb7b) as a potent driver of brown fat development and thermogenesis and cold-induced beige fat formation. Zbtb7b is required for activation of the thermogenic gene program in brown and beige adipocytes. Genetic ablation of Zbtb7b impaired cold-induced transcriptional remodeling in brown fat, rendering mice sensitive to cold temperature, and diminished browning of inguinal white fat. Proteomic analysis revealed a mechanistic link between Zbtb7b and the lncRNA regulatory pathway through which Zbtb7b recruits the brown fat lncRNA 1 (Blnc1)/heterogeneous nuclear ribonucleoprotein U (hnRNPU) ribonucleoprotein complex to activate thermogenic gene expression in adipocytes. These findings illustrate the emerging concept of a protein–lncRNA regulatory network in the control of adipose tissue biology and energy metabolism.

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.

scholarly journals Mapping the Germline and Somatic Mutation Interaction Landscape in Indolent and Aggressive Prostate Cancers

2019 ◽  
Vol 2019 ◽  
pp. 1-15 ◽  
Author(s):  
Tarun Karthik Kumar Mamidi ◽  
Jiande Wu ◽  
Chindo Hicks
Keyword(s):  
Signaling Pathways ◽  
Somatic Mutation ◽  
Regulatory Networks ◽  
Molecular Mechanisms ◽  
Somatic Mutations ◽  
Multiple Gene ◽  
Gene Regulatory ◽  
Aggressive Tumors ◽  
Prostate Cancers ◽  
Mutation Information

Background. A majority of prostate cancers (PCas) are indolent and cause no harm even without treatment. However, a significant proportion of patients with PCa have aggressive tumors that progress rapidly to metastatic disease and are often lethal. PCa develops through somatic mutagenesis, but emerging evidence suggests that germline genetic variation can markedly contribute to tumorigenesis. However, the causal association between genetic susceptibility and tumorigenesis has not been well characterized. The objective of this study was to map the germline and somatic mutation interaction landscape in indolent and aggressive tumors and to discover signatures of mutated genes associated with each type and distinguishing the two types of PCa. Materials and Methods. We integrated germline mutation information from genome-wide association studies (GWAS) with somatic mutation information from The Cancer Genome Atlas (TCGA) using gene expression data from TCGA on indolent and aggressive PCas as the intermediate phenotypes. Germline and somatic mutated genes associated with each type of PCa were functionally characterized using network and pathway analysis. Results. We discovered gene signatures containing germline and somatic mutations associated with each type and distinguishing the two types of PCa. We discovered multiple gene regulatory networks and signaling pathways enriched with germline and somatic mutations including axon guidance, RAR, WINT, MSP-RON, STAT3, PI3K, TR/RxR, and molecular mechanisms of cancer, NF-kB, prostate cancer, GP6, androgen, and VEGF signaling pathways for indolent PCa and MSP-RON, axon guidance, RAR, adipogenesis, and molecular mechanisms of cancer and NF-kB signaling pathways for aggressive PCa. Conclusion. The investigation revealed germline and somatic mutated genes associated with indolent and aggressive PCas and distinguishing the two types of PCa. The study revealed multiple gene regulatory networks and signaling pathways dysregulated by germline and somatic alterations. Integrative analysis combining germline and somatic mutations is a powerful approach to mapping germline and somatic mutation interaction landscape.

Pain processing in the thalamocortical system

e-Neuroforum ◽  
2017 ◽  
Vol 23 (3) ◽  
Author(s):  
Alexander Groh ◽  
Rebecca Mease ◽  
Patrik Krieger
Keyword(s):  
Nervous System ◽  
Animal Models ◽  
Signaling Pathways ◽  
Acute Pain ◽  
Negative Emotion ◽  
Pain Processing ◽  
Pathological Pain ◽  
Thalamocortical System ◽  
Noxious Stimuli ◽  
Lines Of Evidence

AbstractThe transduction of painful stimuli into the experience of pain involves several peripheral and central signaling pathways of the nervous system. The organization of these pathways parallels the main functions of pain: the assessment of noxious stimuli (where, what, how strong), and the negative emotion of unpleasantness. Multiple lines of evidence suggest that the thalamocortical (TC) system, which interprets ascending pain signals, has two main pathways which support these functions. We discuss the structural and functional findings that support the view that the lateral TC pathway is involved in discriminative assessment of pain, while the medial TC pathway gives rise to aversive emotions associated with pain. Our review focuses on acute pain, but we also discuss putative TC maladaptations in humans and animal models of pain that are thought to underlie pathological pain sensations.

scholarly journals Studies on energy metabolism in swine. II. Heat production in piglets at fasting.

1992 ◽  
Vol 29 (1) ◽  
pp. 28-31
Author(s):  
Sumimaro ITOH ◽  
Yashio KURIHARA ◽  
Shuhei IKEDA ◽  
Shin-ichi SUZUKI ◽  
Seiji SUKEMORI ◽  
...  
Keyword(s):  
Energy Metabolism ◽  
Heat Production

Identification of transcription factors MYC and C/EBPβ mediated regulatory networks in heart failure based on GEO dataset

2020 ◽  
Author(s):  
Haiwei Wang ◽  
Xinrui Wang ◽  
Liangpu Xu ◽  
Hua Cao
Keyword(s):  
Heart Failure ◽  
Transcription Factors ◽  
Signaling Pathways ◽  
Signaling Pathway ◽  
Insulin Signaling ◽  
Regulatory Networks ◽  
Target Genes ◽  
Transcriptional Profiling ◽  
Insulin Signaling Pathway ◽  
Failing Heart

Abstract Background: Heart failure is one of leading cause of death worldwide. However, the transcriptional profiling of heart failure is unclear. Moreover, the signaling pathways and transcription factors involving the heart failure development also are largely unknown. Using published Gene Expression Omnibus (GEO) datasets, in the present study, we aim to comprehensively analyze the differentially expressed genes in failing heart tissues, and identified the critical signaling pathways and transcription factors involving heart failure development. Methods: The transcriptional profiling of heart failure was identified from previously published gene expression datasets deposited in GSE5406, GSE16499 and GSE68316. The enriched signaling pathways and transcription factors were analyzed using DAVID website and gene set enrichment analysis (GSEA) assay. The transcriptional networks were created by Cytoscape. Results: Compared with the normal heart tissues, 90 genes were particularly differentially expressed in failing heart tissues, and those genes were associated with multiple metabolism signaling pathways and insulin signaling pathway. Metabolism and insulin signaling pathway were both inactivated in failing heart tissues. Transcription factors MYC and C/EBPβ were both negatively associated with the expression profiling of failing heart tissues in GSEA assay. Moreover, compared with normal heart tissues, MYC and C/EBPβ were down regulated in failing heart tissues. Furthermore, MYC and C/EBPβ mediated downstream target genes were also decreased in failing heart tissues. MYC and C/EBPβ were positively correlated with each other. At last, we constructed MYC and C/EBPβ mediated regulatory networks in failing heart tissues, and identified the MYC and C/EBPβ target genes which had been reported involving the heart failure developmental progress. Conclusions: Our results suggested that metabolism pathways and insulin signaling pathway, transcription factors MYC and C/EBPβ played critical roles in heart failure developmental progress.

scholarly journals Consensus transcriptional regulatory networks of coronavirus-infected human cells

2020 ◽  
Vol 7 (1) ◽  
Author(s):  
Scott A. Ochsner ◽  
Rudolf T. Pillich ◽  
Neil J. McKenna
Keyword(s):  
Signaling Pathways ◽  
Regulatory Networks ◽  
Data Exchange ◽  
Epithelial To Mesenchymal Transition ◽  
Transcriptional Regulatory Networks ◽  
Mesenchymal Transition ◽  
Human Genes ◽  
Transcriptional Regulatory ◽  
Infected Cells ◽  
Key Drivers

Abstract Establishing consensus around the transcriptional interface between coronavirus (CoV) infection and human cellular signaling pathways can catalyze the development of novel anti-CoV therapeutics. Here, we used publicly archived transcriptomic datasets to compute consensus regulatory signatures, or consensomes, that rank human genes based on their rates of differential expression in MERS-CoV (MERS), SARS-CoV-1 (SARS1) and SARS-CoV-2 (SARS2)-infected cells. Validating the CoV consensomes, we show that high confidence transcriptional targets (HCTs) of MERS, SARS1 and SARS2 infection intersect with HCTs of signaling pathway nodes with known roles in CoV infection. Among a series of novel use cases, we gather evidence for hypotheses that SARS2 infection efficiently represses E2F family HCTs encoding key drivers of DNA replication and the cell cycle; that progesterone receptor signaling antagonizes SARS2-induced inflammatory signaling in the airway epithelium; and that SARS2 HCTs are enriched for genes involved in epithelial to mesenchymal transition. The CoV infection consensomes and HCT intersection analyses are freely accessible through the Signaling Pathways Project knowledgebase, and as Cytoscape-style networks in the Network Data Exchange repository.

THERMOGENESIS DUE TO EXERCISE AND COLD IN WARM- AND COLD-ACCLIMATED RATS

1963 ◽  
Vol 41 (1) ◽  
pp. 629-634 ◽  
Author(s):  
J. S. Hart ◽  
L. Jansky
Keyword(s):  
Cold Acclimation ◽  
Heat Production ◽  
Nonshivering Thermogenesis ◽  
Maximum Heat ◽  
Temperature Range ◽  
Sustained Effort ◽  
Extreme Cold

In both warm- and cold-acclimated rats, heat production was measured while the animals were at rest and running at maximum sustained effort at temperatures from 30 °C to those giving maximum thermogenesis. In both these groups, the maximum heat production during exercise did not exceed the maximum at rest in extreme cold. Exercise substituted for shivering in warm-acclimated rats and, at temperatures below 10 °C, resulted in hypothermia. Heat derived from exercise added to nonshivering thermogenesis in cold-acclimated rats above −20 °C. Below −20 °C, exercise substituted for shivering as in warm-acclimated rats at higher temperatures, and the rats became hypothermic. Extension of the temperature range for activity by cold acclimation appears to result from development of nonshivering thermogenesis, which, unlike shivering, is not eliminated by exercise.

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