Circadian variations in gene expression in rat abdominal adipose tissue and relationship to physiology

Circadian rhythms occur in all levels of organization from expression of genes to complex physiological processes. Although much is known about the mechanism of the central clock in the suprachiasmatic nucleus, the regulation of clocks present in peripheral tissues as well as the genes regulated by those clocks is still unclear. In this study, the circadian regulation of gene expression was examined in rat adipose tissue. A rich time series involving 54 animals euthanized at 18 time points within the 24-h cycle (12:12 h light-dark) was performed. mRNA expression was examined with Affymetrix gene array chips and quantitative real-time PCR, along with selected physiological measurements. Transcription factors involved in the regulation of central rhythms were examined, and 13 showed circadian oscillations. Mining of microarray data identified 190 probe sets that showed robust circadian oscillations. Circadian regulated probe sets were further parsed into seven distinct temporal clusters, with >70% of the genes showing maximum expression during the active/dark period. These genes were grouped into eight functional categories, which were examined within the context of their temporal expression. Circadian oscillations were also observed in plasma leptin, corticosterone, insulin, glucose, triglycerides, free fatty acids, and LDL cholesterol. Circadian oscillation in these physiological measurements along with the functional categorization of these genes suggests an important role for circadian rhythms in controlling various functions in white adipose tissue including adipogenesis, energy metabolism, and immune regulation.

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Relationships between circadian rhythms and modulation of gene expression by glucocorticoids in skeletal muscle

AJP Regulatory Integrative and Comparative Physiology ◽

10.1152/ajpregu.90399.2008 ◽

2008 ◽

Vol 295 (4) ◽

pp. R1031-R1047 ◽

Cited By ~ 46

Author(s):

Richard R. Almon ◽

Eric Yang ◽

William Lai ◽

Ioannis P. Androulakis ◽

Svetlana Ghimbovschi ◽

...

Keyword(s):

Gene Expression ◽

Skeletal Muscle ◽

Transcription Factors ◽

Circadian Rhythms ◽

Expression Patterns ◽

Regulation Of Gene Expression ◽

Biological Rhythms ◽

Peripheral Tissues ◽

Rhythmic Expression ◽

Gastrocnemius Muscles

The existence and maintenance of biological rhythms linked to the 24-h light-dark cycle are essential to the health and functioning of an organism. Although much is known concerning central clock mechanisms, much less is known about control in peripheral tissues. In this study, circadian regulation of gene expression was examined in rat skeletal muscle. A rich time series involving 54 animals euthanized at 18 distinct time points within the 24-h cycle was performed, and mRNA expression in gastrocnemius muscles was examined using Affymetrix gene arrays. Data mining identified 109 genes that were expressed rhythmically, which could be grouped into eight distinct temporal clusters within the 24-h cycle. These genes were placed into 11 functional categories, which were examined within the context of temporal expression. Transcription factors involved in the regulation of central rhythms were examined, and eight were found to be rhythmically expressed in muscle. Because endogenous glucocorticoids are a major effector of circadian rhythms, genes identified here were compared with those identified in previous studies as glucocorticoid regulated. Of the 109 genes identified here as circadian rhythm regulated, only 55 were also glucocorticoid regulated. Examination of transcription factors involved in circadian control suggests that corticosterone may be the initiator of their rhythmic expression patterns in skeletal muscle.

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Unusual increase of Scd1 and Elovl6 expression in rat inguinal adipose tissue

Open Life Sciences ◽

10.2478/s11535-012-0007-6 ◽

2012 ◽

Vol 7 (2) ◽

pp. 192-200

Author(s):

Jacek Turyn ◽

Adriana Mika ◽

Piotr Stepnowski ◽

Julian Swierczynski

Keyword(s):

Adipose Tissue ◽

Food Restriction ◽

Metabolic Diseases ◽

Quantitative Polymerase Chain Reaction ◽

Mrna Levels ◽

Gene Expressions ◽

Tissue Mass ◽

Expression Of Genes ◽

Fat Deposits ◽

Rat Adipose Tissue

AbstractIt is generally accepted that the location of body fat deposits may play an important role in the risk of developing some endocrine and metabolic diseases. We have studied the effect of food restriction and food restriction/refeeding, often practiced by individuals trying to lose body weight, on the expression of genes which are associated with obesity and certain metabolic disorders in inguinal, epididymal, and perirenal rat white adipose tissues. Gene expression was analyzed by real time semi-quantitative polymerase chain reaction and by Western blot. We found that prolonged food restriction caused a significant decrease of body and adipose tissue mass as well as the increase of Scd1 and Elovl6 gene expressions in all main rat adipose tissue deposits. Food restriction/refeeding caused increases of: a) Scd1 and Elovl6 mRNA levels in adipose tissue, b) Scd1 protein level and c) desaturation index in adipose tissue. The increased expression of both genes was unusually high in inguinal adipose tissue. The results suggest that the increase of Scd1 and Elovl6 gene expressions in white adipose tissue by prolonged food restriction and prolonged food restriction/refeeding may contribute to accelerated fat recovery that often occurs in individuals after food restriction/refeeding.

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Regulation of gene expression by FSP27 in white and brown adipose tissue

BMC Genomics ◽

10.1186/1471-2164-11-446 ◽

2010 ◽

Vol 11 (1) ◽

pp. 446 ◽

Cited By ~ 25

Author(s):

De Li ◽

Yinxin Zhang ◽

Li Xu ◽

Linkang Zhou ◽

Yue Wang ◽

...

Keyword(s):

Gene Expression ◽

Adipose Tissue ◽

Brown Adipose Tissue ◽

Regulation Of Gene Expression ◽

Brown Adipose

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Cold priming uncouples light- and cold-regulation of gene expression in Arabidopsis thaliana

10.21203/rs.2.19977/v5 ◽

2020 ◽

Author(s):

Andras Bittner ◽

Jörn van Buer ◽

Margarete Baier

Keyword(s):

Gene Expression ◽

Arabidopsis Thaliana ◽

Plant Pathogens ◽

Cold Treatment ◽

Regulation Of Gene Expression ◽

Light Regulation ◽

High Light ◽

Cold Stimulus ◽

Expression Of Genes ◽

Specific Manner

Abstract Background: The majority of stress-sensitive genes responds to cold and high light in the same direction, if plants face the stresses for the first time. As shown recently for a small selection of genes of the core environmental stress response cluster, pre-treatment of Arabidopsis thaliana with a 24 h long 4 °C cold stimulus modifies cold regulation of gene expression for up to a week at 20 °C, although the primary cold effects are reverted within the first 24 h. Such memory-based regulation is called priming. Here, we analyse the effect of 24 h cold priming on cold regulation of gene expression on a transcriptome-wide scale and investigate if and how cold priming affects light regulation of gene expression.Results: Cold-priming affected cold and excess light regulation of a small subset of genes. In contrast to the strong gene co-regulation observed upon cold and light stress in not-primed plants, most priming-sensitive genes were regulated in a stressor-specific manner in cold-primed plant. Furthermore, almost as much genes were inversely regulated as co-regulated by a 24 h long 4 °C cold treatment and exposure to heat-filtered high light (800 µmol quanta m-2 s-1). Gene ontology enrichment analysis revealed that cold priming preferentially supports expression of genes involved in the defence against plant pathogens upon cold triggering. The regulation took place on the cost of the expression of genes involved in growth regulation and transport. On the contrary, cold priming resulted in stronger expression of genes regulating metabolism and development and weaker expression of defence genes in response to high light triggering. qPCR with independently cultivated and treated replicates confirmed the trends observed in the RNASeq guide experiment.Conclusion: A 24 h long priming cold stimulus activates a several days lasting stress memory that controls cold and light regulation of gene expression and adjusts growth and defence regulation in a stressor-specific manner.

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Assessing the Contribution of Relative Macrophage Frequencies to Subcutaneous Adipose Tissue

Frontiers in Nutrition ◽

10.3389/fnut.2021.675935 ◽

2021 ◽

Vol 8 ◽

Author(s):

Marianthi Kalafati ◽

Michael Lenz ◽

Gökhan Ertaylan ◽

Ilja C. W. Arts ◽

Chris T. Evelo ◽

...

Keyword(s):

Gene Expression ◽

Adipose Tissue ◽

Subcutaneous Adipose Tissue ◽

Tissue Cell ◽

Cell Type ◽

Expression Of Genes ◽

Cell Type Composition ◽

Type Composition ◽

Adipose Tissue Cell ◽

Subcutaneous Adipose

Background: Macrophages play an important role in regulating adipose tissue function, while their frequencies in adipose tissue vary between individuals. Adipose tissue infiltration by high frequencies of macrophages has been linked to changes in adipokine levels and low-grade inflammation, frequently associated with the progression of obesity. The objective of this project was to assess the contribution of relative macrophage frequencies to the overall subcutaneous adipose tissue gene expression using publicly available datasets.Methods: Seven publicly available microarray gene expression datasets from human subcutaneous adipose tissue biopsies (n = 519) were used together with TissueDecoder to determine the adipose tissue cell-type composition of each sample. We divided the subjects in four groups based on their relative macrophage frequencies. Differential gene expression analysis between the high and low relative macrophage frequencies groups was performed, adjusting for sex and study. Finally, biological processes were identified using pathway enrichment and network analysis.Results: We observed lower frequencies of adipocytes and higher frequencies of adipose stem cells in individuals characterized by high macrophage frequencies. We additionally studied whether, within subcutaneous adipose tissue, interindividual differences in the relative frequencies of macrophages were reflected in transcriptional differences in metabolic and inflammatory pathways. Adipose tissue of individuals with high macrophage frequencies had a higher expression of genes involved in complement activation, chemotaxis, focal adhesion, and oxidative stress. Similarly, we observed a lower expression of genes involved in lipid metabolism, fatty acid synthesis, and oxidation and mitochondrial respiration.Conclusion: We present an approach that combines publicly available subcutaneous adipose tissue gene expression datasets with a deconvolution algorithm to calculate subcutaneous adipose tissue cell-type composition. The results showed the expected increased inflammation gene expression profile accompanied by decreased gene expression in pathways related to lipid metabolism and mitochondrial respiration in subcutaneous adipose tissue in individuals characterized by high macrophage frequencies. This approach demonstrates the hidden strength of reusing publicly available data to gain cell-type-specific insights into adipose tissue function.

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Effect of hypothyroidism on adenylyl cyclase activity and subtype gene expression in brown adipose tissue

AJP Regulatory Integrative and Comparative Physiology ◽

10.1152/ajpregu.1997.273.2.r762 ◽

1997 ◽

Vol 273 (2) ◽

pp. R762-R767 ◽

Cited By ~ 2

Author(s):

A. Chaudhry ◽

J. G. Granneman

Keyword(s):

Gene Expression ◽

Adipose Tissue ◽

Brown Adipose Tissue ◽

Adenylyl Cyclase ◽

Regulation Of Gene Expression ◽

Mrna Levels ◽

Adrenergic Stimulation ◽

Functional Responses ◽

Synergistic Interactions ◽

Brown Adipose

Brown adipose tissue (BAT) expresses several adenylyl cyclase (AC) subtypes, and adrenergic stimulation selectively upregulates AC-III gene expression. Previous studies have described synergistic interactions between the sympathetic nervous system (SNS) and 3,5,3'-triiodothyronine (T3) on the regulation of gene expression in BAT. Because adrenergic stimulation also increases the activity of BAT type II thyroxine 5'-deiodinase (DII) and local T3 generation is important for many functional responses in BAT, we examined the effects of thyroid hormone status on the expression of various AC subtypes. Hypothyroidism selectively increased AC-III mRNA levels in BAT but not in white adipose tissue. Of the other subtypes examined, hypothyroidism did not alter AC-VI mRNA levels and slightly reduced AC-IX mRNA levels in BAT. The increase in AC-III expression was paralleled by an increase in forskolin-stimulated AC activity in BAT membranes. Sympathetic denervation of BAT abolished the increase in both AC activity and AC-III mRNA expression produced by hypothyroidism, but did not affect the expression of other subtypes. Surgical denervation also prevented the induction of AC-III in the cold-stressed euthyroid rat, but injections of T3 failed to alter AC-III expression in intact or denervated BAT. Our results indicate that T3 does not directly affect expression of AC-III. Rather, hypothyroidism increases BAT AC-III expression indirectly via an increase in sympathetic stimulation. Furthermore, our results strongly indicate that the increase in AC activity in hypothyroid BAT is due to increased expression of AC-III.

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Citrullination – small change with a great consequence

Folia Biologica et Oecologica ◽

10.2478/fobio-2013-0003 ◽

2013 ◽

Vol 9 ◽

pp. 17-25 ◽

Cited By ~ 2

Author(s):

Mariusz Gogól

Keyword(s):

Rheumatoid Arthritis ◽

Gene Expression ◽

Multiple Sclerosis ◽

Positive Charge ◽

Regulation Of Gene Expression ◽

Slight Modification ◽

Post Translational Modifications ◽

Myelin Sheaths ◽

Physiological Processes ◽

Small Change

Citrullination is one of the possible post-translational modifications of proteins. It is based on a conversion of L-arginine residue (L-Arg) to L-citrulline residue (L-Cit). The reaction is catalyzed by peptidylarginine deiminases (PAD). The change of L-Arg imino moiety results in a loss of a positive charge. This slight modification can contribute to significant changes in physicochemical properties of proteins, which may also cause a change of their functions. Citrullination is the modification observed in physiological processes such as epidermal keratinization, regulation of gene expression and the reorganization of myelin sheaths. The changes in the efficacy of citrullination may contribute to the pathogenesis of many different diseases including: psoriasis, multiple sclerosis, rheumatoid arthritis and cancer.

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Monocyte Chemoattractant Protein-1 in Subcutaneous Abdominal Adipose Tissue: Characterization of Interstitial Concentration and Regulation of Gene Expression by Insulin

The Journal of Clinical Endocrinology & Metabolism ◽

10.1210/jc.2006-2814 ◽

2007 ◽

Vol 92 (7) ◽

pp. 2688-2695 ◽

Cited By ~ 38

Author(s):

Giuseppe Murdolo ◽

Ann Hammarstedt ◽

Madeléne Sandqvist ◽

Martin Schmelz ◽

Christian Herder ◽

...

Keyword(s):

Gene Expression ◽

Adipose Tissue ◽

Regulation Of Gene Expression ◽

Whole Body ◽

Mrna Levels ◽

Abdominal Adipose Tissue ◽

Monocyte Chemoattractant Protein 1 ◽

Monocyte Chemoattractant ◽

Monocyte Chemoattractant Protein ◽

Adipose Organ

Abstract Context: The chemokine monocyte chemoattractant protein-1 (MCP-1) is implicated in obesity-associated chronic inflammation, insulin resistance, and atherosclerosis. Objectives: The objectives of this study were to: 1) characterize the interstitial levels and the gene expression of MCP-1 in the sc abdominal adipose tissue (SCAAT), 2) elucidate the response of MCP-1 to acute hyperinsulinemia, and 3) determine the relationship between MCP-1 and arterial stiffness. Design: Nine lean (L) and nine uncomplicated obese (OB) males were studied in the fasting state and during a euglycemic-hyperinsulinemic clamp combined with the microdialysis technique. Interstitial and serum MCP-1 (iMCP-1 and sMCP-1, respectively) levels, pulse wave analysis, and SCAAT biopsies were characterized at baseline and after hyperinsulinemia. Results: OB showed elevated sMCP-1 (P < 0.01) but similar iMCP-1 levels as compared with L. Basal iMCP-1 concentrations were considerably higher than sMCP-1 (P < 0.0001), and a gradient between iMCP-1 and sMCP-1 levels was maintained throughout the hyperinsulinemia. At baseline, SCAAT gene expression profile revealed a “co-upregulation” of MCP-1, MCP-2, macrophage inflammatory protein-1α, and CD68 in OB, and whole-body glucose disposal inversely correlated with the MCP-1 gene expression. After hyperinsulinemia, MCP-1 and MCP-2 mRNA levels significantly increased in L, but not in OB. Finally, sMCP-1 excess in the OB positively correlated with the stiffer vasculature. Conclusions: These observations demonstrate similar interstitial concentrations and a differential gene response to hyperinsulinemia of MCP-1 in the SCAAT from L and OB individuals. In human obesity, we suggest the SCAAT MCP-1 gene overexpression as a biomarker of an “inflamed” adipose organ and impaired glucose metabolism.

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Imputed gene associations identify replicable trans-acting genes enriched in transcription pathways and complex traits

10.1101/471748 ◽

2018 ◽

Cited By ~ 1

Author(s):

Heather E. Wheeler ◽

Sally Ploch ◽

Alvaro N. Barbeira ◽

Rodrigo Bonazzola ◽

Angela Andaleon ◽

...

Keyword(s):

Gene Expression ◽

Genetic Variation ◽

Complex Traits ◽

Target Gene ◽

Target Genes ◽

Regulation Of Gene Expression ◽

Nucleic Acid Binding ◽

Expression Of Genes ◽

Gene Associations ◽

Made In

AbstractRegulation of gene expression is an important mechanism through which genetic variation can affect complex traits. A substantial portion of gene expression variation can be explained by both local (cis) and distal (trans) genetic variation. Much progress has been made in uncovering cis-acting expression quantitative trait loci (cis-eQTL), but trans-eQTL have been more difficult to identify and replicate. Here we take advantage of our ability to predict the cis component of gene expression coupled with gene mapping methods such as PrediXcan to identify high confidence candidate trans-acting genes and their targets. That is, we correlate the cis component of gene expression with observed expression of genes in different chromosomes. Leveraging the shared cis-acting regulation across tissues, we combine the evidence of association across all available GTEx tissues and find 2356 trans-acting/target gene pairs with high mappability scores. Reassuringly, trans-acting genes are enriched in transcription and nucleic acid binding pathways and target genes are enriched in known transcription factor binding sites. Interestingly, trans-acting genes are more significantly associated with selected complex traits and diseases than target or background genes, consistent with percolating trans effects. Our scripts and summary statistics are publicly available for future studies of trans-acting gene regulation.

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Integrative analysis of glucometabolic traits, adipose tissue DNA methylation and gene expression identifies epigenetic regulatory mechanisms of insulin resistance and obesity in African Americans

10.2337/figshare.12896636.v1 ◽

2020 ◽

Author(s):

Ada Admin ◽

Neeraj K. Sharma ◽

Mary E. Comeau ◽

Dennis Montoya ◽

Matteo Pellegrini ◽

...

Keyword(s):

Gene Expression ◽

Insulin Resistance ◽

Dna Methylation ◽

Adipose Tissue ◽

Insulin Sensitivity ◽

African Americans ◽

Association Studies ◽

Regulation Of Gene Expression ◽

Transcript Level ◽

Matsuda Index

Decline in insulin sensitivity due to dysfunction of adipose tissue (AT) is one of the earliest pathogenic events in Type 2 Diabetes. We hypothesize that differential DNA methylation (DNAm) controls insulin sensitivity and obesity by modulating transcript expression in AT. Integrating AT DNAm profiles with transcript profile data measured in a cohort of 230 African Americans from AAGMEx cohort, we performed cis-expression quantitative trait methylation (cis-eQTM) analysis to identify epigenetic regulatory loci for glucometabolic trait-associated transcripts. We identified significantly associated CpG-regions for 82 transcripts (FDR-P<0.05). The strongest eQTM locus was observed for the proopiomelanocortin (POMC; r= -0.632, P= 4.70X10-27) gene. Epigenome-wide association studies (EWAS) further identified 155, 46, and 168 CpG regions associated (FDR-P <0.05) with Matsuda index, SI and BMI, respectively. Intersection of EWAS, transcript level to trait association, and eQTM results, followed by causal inference test identified significant eQTM loci for 23 genes that were also associated with Matsuda index, SI and/or BMI in EWAS. These associated genes include FERMT3, ITGAM, ITGAX, and POMC. In summary, applying an integrative multi-omics approach, our study provides evidence for DNAm-mediated regulation of gene expression at both previously identified and novel loci for many key AT transcripts influencing insulin resistance and obesity.

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