scholarly journals SIRT1 Exerts Anti-Inflammatory Effects and Improves Insulin Sensitivity in Adipocytes

2008 ◽  
Vol 29 (5) ◽  
pp. 1363-1374 ◽  
Author(s):  
Takeshi Yoshizaki ◽  
Jill C. Milne ◽  
Takeshi Imamura ◽  
Simon Schenk ◽  
Noriyuki Sonoda ◽  
...  
Keyword(s):  
Gene Expression ◽  
Glucose Uptake ◽  
Insulin Signaling ◽  
Energy Homeostasis ◽  
Expression Profiles ◽  
Gene Expression Profiles ◽  
Serine Phosphorylation ◽  
Cellular Functions ◽  
Necrosis Factor Alpha ◽  
Anti Inflammatory

ABSTRACT SIRT1 is a prominent member of a family of NAD+-dependent enzymes and affects a variety of cellular functions ranging from gene silencing, regulation of the cell cycle and apoptosis, to energy homeostasis. In mature adipocytes, SIRT1 triggers lipolysis and loss of fat content. However, the potential effects of SIRT1 on insulin signaling pathways are poorly understood. To assess this, we used RNA interference to knock down SIRT1 in 3T3-L1 adipocytes. SIRT1 depletion inhibited insulin-stimulated glucose uptake and GLUT4 translocation. This was accompanied by increased phosphorylation of JNK and serine phosphorylation of insulin receptor substrate 1 (IRS-1), along with inhibition of insulin signaling steps, such as tyrosine phosphorylation of IRS-1, and phosphorylation of Akt and ERK. In contrast, treatment of cells with specific small molecule SIRT1 activators led to an increase in glucose uptake and insulin signaling as well as a decrease in serine phosphorylation of IRS-1. Moreover, gene expression profiles showed that SIRT1 expression was inversely related to inflammatory gene expression. Finally, we show that treatment of 3T3-L1 adipocytes with a SIRT1 activator attenuated tumor necrosis factor alpha-induced insulin resistance. Taken together, these data indicate that SIRT1 is a positive regulator of insulin signaling at least partially through the anti-inflammatory actions in 3T3-L1 adipocytes.

scholarly journals Adipose gene expression profiles reveal novel insights into the adaptation of northern Eurasian semi-domestic reindeer (Rangifer tarandus)

2021 ◽  
Author(s):  
Melak Weldenegodguad ◽  
Kisun Pokharel ◽  
Laura Niiranen ◽  
Päivi Soppela ◽  
Innokentyi Ammosov ◽  
...  
Keyword(s):  
Gene Expression ◽  
Adipose Tissue ◽  
Energy Metabolism ◽  
Energy Homeostasis ◽  
Rangifer Tarandus ◽  
Expression Profiles ◽  
Gene Expression Profiles ◽  
Northern Eurasia ◽  
Adipose Tissues ◽  
Arctic Conditions

AbstractReindeer (Rangifer tarandus) are semi-domesticated animals adapted to the challenging arctic conditions of northern Eurasia. Adipose tissues play a crucial role in animals living in northern environments by altering gene expression in their tissues to regulate energy homeostasis and thermogenic activity. Here, we performed transcriptome profiling by RNA sequencing of adipose tissues from three different anatomical depots: metacarpal (bone marrow), perirenal, and prescapular fat in Finnish and Even reindeer (in Sakha) during two seasonal time points (spring and winter). On average 36.5 million pair-ended clean reads were obtained for each sample, and a total of 16,362 genes were expressed in our data. Gene expression profiles in metacarpal tissue were distinct and clustered separately from perirenal and prescapular adipose tissues. Notably, metacarpal adipose tissue appeared to have a significant role in the regulation of the energy metabolism of reindeer in spring when their nutritional condition is poor after winter. During spring, when the animals are in less optimal condition, genes associated with the immune system (e.g., CCL2, CCL11, CXCL14, IGSF3, IGHM, IGLC7, IGKC, JCHAIN, and IGSF10) were upregulated in the perirenal and prescapular adipose tissue, while genes involved in energy metabolism (e.g., ACOT2, APOA1, ANGPTL1, ANGPTL8, ELOVL7, MSMO1, PFKFB1, and ST3GAL6) were upregulated in metacarpal tissue. Even reindeer harboured relatively fewer significantly differentially expressed genes than Finnish reindeer, irrespective of the season, possibly owing to climatic and management differences. Moreover, blood and tissue parameters reflecting general physiological and metabolic status showed less seasonal variation in Even reindeer than in Finnish reindeer. This study identified adipose candidate genes potentially involved in immune response, fat deposition, energy metabolism, development, cell growth, and organogenesis. Taken together, this study provides new information on the mechanisms by which reindeer adapt to less optimal arctic conditions.

Abstract 149: Regulation of Pathogen-Associated Molecular Pattern Recognition by the Apo A-I Mimetic Peptide 4F

2012 ◽  
Vol 32 (suppl_1) ◽  
Author(s):  
Geeta Datta ◽  
David K Crossman ◽  
Lesley E Smythies ◽  
M N Palgunachari ◽  
Manjula Chaddha ◽  
...  
Keyword(s):  
Gene Expression ◽  
Inflammatory Responses ◽  
Expression Profiles ◽  
Gene Expression Profiles ◽  
Rna Isolation ◽  
Mimetic Peptide ◽  
M1 Macrophage ◽  
Vehicle Treatment ◽  
Anti Inflammatory ◽  
Pre Treatment

The apolipoprotein A-I (apoA-I) mimetic peptide 4F displays prominent anti-inflammatory properties, including the ability to reduce vascular macrophage content. Macrophages are a heterogenous group of cells that are represented by two principal phenotypes, the classically-activated M1 macrophage and an alternatively-activated M2 phenotype. We previously reported that apoA-I and 4F favor the differentiation of human monocytes to an anti-inflammatory phenotype similar to that displayed by M2 macrophages. Further, 4F treatment attenuated LPS-induced inflammatory responses in monocyte-derived macrophages (MDMs). In the current study, we investigated effects of 4F and vehicle on LPS-induced gene expression in human MDMs by microarray analysis. RNA isolation, labeling and hybridization were performed, and the transcriptional profile was examined using the Human Gene ST 1.0 Affymetrix chip. Analysis of MDM gene expression profiles revealed that 4F modulated mRNA expression for 1099 genes (± 2-fold change, p<0.05), of which 149 genes regulated inflammatory responses. LPS treatment of MDMs significantly up-regulated genes encoding Toll-like receptors (TLR1, 2, 4, 6, and 8) compared to vehicle treatment. These responses were attenuated by 4F treatment. MyD88, CD14, IRAK4, TRAF6, TRAF3, MALT1 and IKBKB, genes that modulate NF-κB activation and subsequent cytokine synthesis, were also reduced by 4F. Corroborating this, FACS analyses showed that pre-treatment of MDMs with 4F reduced the LPS-dependent phosphorylation of NF-κB by 70% compared to vehicle treatment. These 4F-induced responses were also associated with a reduction in TNF-α and IL-6 secretion. These data suggest that an important anti-inflammatory mechanism of 4F action may be to down-regulate genes involved in the TLR signaling pathway, thus attenuating the responsiveness of macrophages to LPS and other pathogen-associated molecular patterns (PAMPs).

scholarly journals Brucella melitensis Triggers Time-Dependent Modulation of Apoptosis and Down-Regulation of Mitochondrion-Associated Gene Expression in Mouse Macrophages

2006 ◽  
Vol 74 (9) ◽  
pp. 5035-5046 ◽  
Author(s):  
Yongqun He ◽  
Sherry Reichow ◽  
Sheela Ramamoorthy ◽  
Xicheng Ding ◽  
Raju Lathigra ◽  
...  
Keyword(s):  
Gene Expression ◽  
Brucella Melitensis ◽  
Expression Profiles ◽  
Gene Expression Profiles ◽  
Transcriptional Response ◽  
Necrosis Factor Alpha ◽  
Mitochondrial Functions ◽  
Mouse Macrophages ◽  
External Stimuli ◽  
Infection Stage

ABSTRACT Brucella spp. are facultative intracellular bacteria that cause brucellosis in humans and other animals. Brucella spp. are taken up by macrophages, and the outcome of the macrophage-Brucella interaction is a basis for establishment of a chronic Brucella infection. Microarrays were used to analyze the transcriptional response of the murine macrophage-like J774.A1 cell line to infection with virulent Brucella melitensis strain 16M. It was found that most significant changes in macrophage gene transcription happened early following infection, and global macrophage gene expression profiles returned to normal between 24 and 48 h postinfection. These findings support the observation that macrophages kill the majority of Brucella cells at the early infection stage, but the surviving Brucella cells are able to avoid macrophage brucellacidal activity inside replicative phagosomes at the later infection stage. At 4 h postinfection, macrophage genes involved in cell growth, metabolism, and responses to endogenous stimuli were down-regulated, while the inflammatory response (e.g., tumor necrosis factor alpha and Toll-like receptor 2), the complement system, the responses to external stimuli, and other immune responses were up-regulated. It is likely that the most active brucellacidal activity happened between 0 and 4 h postinfection. Mitochondrion-associated gene expression, which is involved in protein synthesis and transport, electron transfer, and small-molecule transfer, and many other mitochondrial functions were significantly down-regulated at 4 h postinfection. Although there were both pro- and antiapoptosis effects, B. melitensis 16M appears to inhibit apoptosis of macrophages by blocking release of cytochrome c and production of reactive oxygen species in the mitochondria, thus preventing activation of caspase cascades.

179. PURIFICATION AND CHARACTERISATION OF MOUSE TESTICULAR MACROPHAGES: GENE EXPRESSION RESPONSE TO LIPOPOLYSACCHARIDE ACTIVATION INDICATES AN IMMUNOSUPPRESSIVE PHENOTYPE

2010 ◽  
Vol 22 (9) ◽  
pp. 97
Author(s):  
W. R. Winnall ◽  
J. Gould ◽  
J. A. Muir ◽  
P. Hertzog ◽  
M. P. Hedger
Keyword(s):  
Gene Expression ◽  
Microarray Analysis ◽  
Inflammatory Mediators ◽  
Inflammatory Cytokine ◽  
Transforming Growth Factor ◽  
Expression Profiles ◽  
Gene Expression Profiles ◽  
Gene Expression Response ◽  
Anti Inflammatory ◽  
Testicular Macrophages

Studies on rat testicular macrophages (TMs) have indicated that these cells play an important role in testis function by supporting the immunosuppressive environment that protects developing germ cells and by responding to pathogens. By comparison, mouse TMs are essentially uncharacterised due to difficulties in isolating sufficient cells for study. We have established a technique for isolating 95% pure TMs from adult mice by differential adherence. Mouse TMs were cultured for 3h with saline, 10 or 100 ng/mL lipopolysaccharide (LPS) and compared with resident peritoneal macrophages (PMs) and bone marrow-derived macrophages (BMMs). Expression of inflammatory regulators was determined using real-time Q-PCR and AgilentTM microarray analysis. Microarray analysis indicated that each macrophage type displayed very distinct gene expression profiles. There were 526 genes uniquely expressed in TMs at basal levels compared with the other macrophages and 268 genes uniquely expressed by TMs after LPS treatment. Q-PCR determined that LPS induced expression of the anti-inflammatory cytokine interleukin (IL)-10 in each of the macrophage types, with BMMs the strongest responders. LPS stimulated IL-10 mRNA approximately 100-fold in TMs, but only 20-fold in PMs. The anti-inflammatory transforming growth factor-β1 was not significantly induced at this time-point in any macrophage type. In terms of pro-inflammatory mediators, the TM response to LPS was always lower compared to the BMMs. Compared to PMs, the responses of TMs were similar for the hallmark pro-inflammatory cytokine tumour necrosis factor- a, but 40% less for IL-1β. TMs were also deficient in production of IL-6 and cyclooxygenase-2 and IL-12. TMs were therefore relatively strong responders to LPS in terms of IL-10, but weak responders in terms of pro-inflammatory mediators, indicating an immunosuppressive phenotype. The isolation and gene measurement methods established in this study will allow us to use knockout and transgenic mouse models to determine the role for TMs in testicular inflammation/fibrosis models.

Deciphering cellular functions of protein phosphatases by comparison of gene expression profiles in Saccharomyces cerevisiae

2010 ◽  
Vol 109 (5) ◽  
pp. 433-441 ◽  
Author(s):  
Masataka Hirasaki ◽  
Fumika Nakamura ◽  
Kazuo Yamagishi ◽  
Minori Numamoto ◽  
Yukiko Shimada ◽  
...  
Keyword(s):  
Gene Expression ◽  
Saccharomyces Cerevisiae ◽  
Expression Profiles ◽  
Protein Phosphatases ◽  
Gene Expression Profiles ◽  
Cellular Functions

scholarly journals miRNA-Based Therapeutics in the Era of Immune-Checkpoint Inhibitors

2021 ◽  
Vol 14 (2) ◽  
pp. 89
Author(s):  
Florian Huemer ◽  
Michael Leisch ◽  
Roland Geisberger ◽  
Nadja Zaborsky ◽  
Richard Greil
Keyword(s):  
Gene Expression ◽  
Immune Checkpoint ◽  
Current Knowledge ◽  
Checkpoint Inhibitors ◽  
Expression Profiles ◽  
Gene Expression Profiles ◽  
Cellular Functions ◽  
Gene Transcripts ◽  
A Cell ◽  
Cell Type Specific

MicroRNAs (miRNAs) are small non-coding RNAs that regulate gene expression by binding to complementary target regions on gene transcripts. Thus, miRNAs fine-tune gene expression profiles in a cell-type-specific manner and thereby regulate important cellular functions, such as cell growth, proliferation and cell death. MiRNAs are frequently dysregulated in cancer cells by several mechanisms, which significantly affect the course of the disease. In this review, we summarize the current knowledge on how dysregulated miRNAs contribute to cancer and how miRNAs can be exploited as predictive factors and therapeutic targets, particularly in regard to immune-checkpoint inhibitor therapies.

1327: Gene Expression Profiles in Benign Prostatic Hyperplasia

2004 ◽  
Vol 171 (4S) ◽  
pp. 349-350
Author(s):  
Gaelle Fromont ◽  
Michel Vidaud ◽  
Alain Latil ◽  
Guy Vallancien ◽  
Pierre Validire ◽  
...  
Keyword(s):  
Gene Expression ◽  
Benign Prostatic Hyperplasia ◽  
Expression Profiles ◽  
Gene Expression Profiles ◽  
Prostatic Hyperplasia
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