Zinc-α2-Glycoprotein Knockout Influenced Genes Expression Profile in Adipose Tissue and Decreased the Lipid Mobilizing After Dexamethasone Treatment in Mice

2020 ◽  
Vol 52 (10) ◽  
pp. 755-763
Author(s):  
Wenge Zhang ◽  
Yu Qiao ◽  
Fulei Qi ◽  
Qingyi Shen ◽  
Ruqian Zhao ◽  
...  
Keyword(s):  
Gene Expression ◽  
Adipose Tissue ◽  
Fatty Acid ◽  
Lipid Metabolism ◽  
Gene Expression Profile ◽  
Expression Profile ◽  
Visceral Fat ◽  
Fatty Acid Synthase ◽  
Wild Type ◽  
Genes Expression

AbstractZinc-α2-glycoprotein (ZAG), as an adipokine, plays an important role in lipid metabolism. However, its influence on whole gene expression profile in adipose tissue is not known. Under stress condition, how ZAG affects the lipid metabolism is also unclear. Therefore, in this study ZAG systemic knockout (KO) mice were used as a model to reveal the genes expression profile in visceral fat tissues of ZAG KO mice and wild-type mice by genome-wide microarray screening. Then dexamethasone (DEX) was used to explore the effect of ZAG deletion on body fat metabolism under stress. Our results showed that 179 genes were differentially expressed more than 1.5 times between ZAG KO mice and wild type mice, of which 26 genes were upregulated dramatically and 153 genes were significantly downregulated. Under DEX simulated stress, ZAG systemic knockout in vivo resulted in a markedly decrease of triglycerides (TG) and nonesterified fatty acid (NEFA) content in in plasma. Similarly, for lipid catabolism, ZAG KO led to a significant increase of phosphorylated HSL (p-HSL) protein and a rising tendency of adipose triglyceride lipase (ATGL) protein relative to those of the DEX group. For lipid anabolism, fatty acid synthase (FAS) and adiponectin protein expression in visceral fat rose notably in ZAG KO mice after DEX treatment. In conclusion, ZAG knockout can affect the gene expression profile of adipose tissue, reduce elevated TG and NEFA levels in plasma, and alter lipid metabolism under DEX treatment. These findings provide new insights into the mechanism of lipid metabolic disorders in response to stress.

scholarly journals Dysregulation of Lipid Metabolism in Mkp-1 Deficient Mice during Gram-Negative Sepsis

2018 ◽  
Vol 19 (12) ◽  
pp. 3904 ◽  
Author(s):  
Jinhui Li ◽  
Xiantao Wang ◽  
William Ackerman ◽  
Abel Batty ◽  
Sean Kirk ◽  
...  
Keyword(s):  
Gene Expression ◽  
Fatty Acid ◽  
Lipid Metabolism ◽  
Gene Expression Profile ◽  
Expression Profile ◽  
Underlying Mechanism ◽  
Mitogen Activated Protein Kinase ◽  
Acid Uptake ◽  
Gram Negative ◽  
E Coli

Mitogen-activated protein kinase phosphatase (Mkp)-1 exerts its anti-inflammatory activities during Gram-negative sepsis by deactivating p38 and c-Jun N-terminal kinase (JNK). We have previously shown that Mkp-1+/+ mice, but not Mkp-1−/− mice, exhibit hypertriglyceridemia during severe sepsis. However, the regulation of hepatic lipid stores and the underlying mechanism of lipid dysregulation during sepsis remains an enigma. To understand the molecular mechanism underlying the sepsis-associated metabolic changes and the role of Mkp-1 in the process, we infected Mkp-1+/+ and Mkp-1−/− mice with Escherichia coli i.v., and assessed the effects of Mkp-1 deficiency on tissue lipid contents. We also examined the global gene expression profile in the livers via RNA-seq. We found that in the absence of E. coli infection, Mkp-1 deficiency decreased liver triglyceride levels. Upon E. coli infection, Mkp-1+/+ mice, but not Mkp-1−/− mice, developed hepatocyte ballooning and increased lipid deposition in the livers. E. coli infection caused profound changes in the gene expression profile of a large number of proteins that regulate lipid metabolism in wildtype mice, while these changes were substantially disrupted in Mkp-1−/− mice. Interestingly, in Mkp-1+/+ mice E. coli infection resulted in downregulation of genes that facilitate fatty acid synthesis but upregulation of Cd36 and Dgat2, whose protein products mediate fatty acid uptake and triglyceride synthesis, respectively. Taken together, our studies indicate that sepsis leads to a substantial change in triglyceride metabolic gene expression programs and Mkp-1 plays an important role in this process.

scholarly journals Cellular retinol-binding protein type III is a PPARγ target gene and plays a role in lipid metabolism

2008 ◽  
Vol 295 (6) ◽  
pp. E1358-E1368 ◽  
Author(s):  
Cynthia F. Zizola ◽  
Gary J. Schwartz ◽  
Silke Vogel
Keyword(s):  
Adipose Tissue ◽  
Fatty Acid ◽  
Lipid Metabolism ◽  
Free Fatty Acid ◽  
Target Gene ◽  
Binding Protein ◽  
Retinol Binding Protein ◽  
Wild Type ◽  
Type Iii ◽  
Cellular Retinol Binding Protein

Cellular retinol-binding protein (CRBP) type III (CRBP-III) belongs to the family of intracellular lipid-binding proteins, which includes the adipocyte-binding protein aP2. In the cytosol, CRBP-III binds retinol, the precursor of retinyl ester and the active metabolite retinoic acid. The goal of the present work is to understand the regulation of CRBP-III expression and its role in lipid metabolism. Using EMSAs, luciferase reporter assays, and chromatin immunoprecipitation assays, we found that CRBP-III is a direct target of peroxisome proliferator-activated receptor-γ (PPARγ). Moreover, CRBP-III expression was induced in adipose tissue of mice after treatment with the PPARγ agonist rosiglitazone. To examine a potential role of CRBP-III in regulating lipid metabolism in vivo, CRBP-III-deficient (C-III-KO) mice were maintained on a high-fat diet (HFD). Hepatic steatosis was decreased in HFD-fed C-III-KO compared with HFD-fed wild-type mice. These differences were partly explained by decreased serum free fatty acid levels and decreased free fatty acid efflux from adipose tissue of C-III-KO mice. In addition, the lack of CRBP-III was associated with reduced food intake, increased respiratory energy ratio, and altered body composition, with decreased adiposity and increased lean body mass. Furthermore, expression of genes involved in mitochondrial fatty acid oxidation in brown adipose tissue was increased in C-III-KO mice, and C-III-KO mice were more cold tolerant than wild-type mice fed an HFD. In summary, we demonstrate that CRBP-III is a PPARγ target gene and plays a role in lipid and whole body energy metabolism.

scholarly journals Cultured Human Adipose Tissue Pericytes and Mesenchymal Stromal Cells Display a Very Similar Gene Expression Profile

2015 ◽  
Vol 24 (23) ◽  
pp. 2822-2840 ◽  
Author(s):  
Lindolfo da Silva Meirelles ◽  
Tathiane Maistro Malta ◽  
Virgínia Mara de Deus Wagatsuma ◽  
Patrícia Viana Bonini Palma ◽  
Amélia Goes Araújo ◽  
...  
Keyword(s):  
Gene Expression ◽  
Adipose Tissue ◽  
Gene Expression Profile ◽  
Mesenchymal Stromal Cells ◽  
Expression Profile ◽  
Stromal Cells ◽  
Human Adipose Tissue ◽  
Similar Gene Expression Profile ◽  
Similar Gene

scholarly journals Effect of mild restriction of food intake on gene expression profile in the liver of young rats: reference data for in vivo nutrigenomics study

2010 ◽  
Vol 104 (7) ◽  
pp. 941-950 ◽  
Author(s):  
Kenji Saito ◽  
Yutaka Ohta ◽  
Manabu Sami ◽  
Tomomasa Kanda ◽  
Hisanori Kato
Keyword(s):  
Gene Expression ◽  
Food Intake ◽  
Gene Expression Profile ◽  
Expression Profile ◽  
Fatty Acid Synthase ◽  
Reference Data ◽  
Global Gene Expression ◽  
Energy Restriction ◽  
Genes Encoding

Recent transcriptomics studies on the effect of long-term or severe energy restriction (ER) have revealed that many genes are dynamically modulated by this condition in rodents. The present study was conducted to define the global gene expression profile in response to mild ER treatment. Growing rats were fed with reduced amount of diet (5–30 % ER) for 1 week or 1 month. Using DNA microarray analysis of the liver, seventy-two genes that were consistently changed through the different ER levels were identified. Many were related to lipid metabolism including genes encoding key enzymes such as carnitine palmitoyltransferase 1 and fatty acid synthase. Interestingly, a number of genes were altered even by 5 % ER for 1 week where no differences in weight gain were observed. The information obtained in the present study can be used as a valuable reference data source in the transcriptomics studies of food and nutrition in which subtle differences in food intake sometimes hinder appropriate interpretation of the data.

Altered complement gene expression profile of adipose tissue and adipocytes in obesity: A monozygotic twin study

Immunobiology ◽  
2016 ◽  
Vol 221 (10) ◽  
pp. 1187
Author(s):  
Sanna Kaye ◽  
Anna Hanttu ◽  
A. Inkeri Lokki ◽  
Eija Nissilä ◽  
Sini Heinonen ◽  
...  
Keyword(s):  
Gene Expression ◽  
Adipose Tissue ◽  
Gene Expression Profile ◽  
Expression Profile ◽  
Twin Study ◽  
Monozygotic Twin ◽  
Complement Gene

scholarly journals The transcriptome of early GGT/KRT19-positive hepatocellular carcinoma reveals a downregulated gene expression profile associated with fatty acid metabolism

Genomics ◽  
2021 ◽  
Author(s):  
María Paulette Castro-Gil ◽  
Julia Esperanza Torres-Mena ◽  
Rosa M. Salgado ◽  
Said A. Muñoz-Montero ◽  
José Michael Martínez-Garcés ◽  
...  
Keyword(s):  
Gene Expression ◽  
Hepatocellular Carcinoma ◽  
Fatty Acid ◽  
Gene Expression Profile ◽  
Expression Profile ◽  
Fatty Acid Metabolism ◽  
Acid Metabolism ◽  
Downregulated Gene

The Interaction of MOZ-TIF2 with Histone Chaperon Proteins CAF-1A and Asf1b Alters MOZ Regulated Gene Expression.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 2208-2208
Author(s):  
Hong Yin ◽  
Jonathan Glass ◽  
Kerry L. Blanchard
Keyword(s):  
Gene Expression ◽  
Gene Expression Profile ◽  
Expression Profile ◽  
Global Gene Expression ◽  
Chromatin Assembly ◽  
Wild Type ◽  
Terminal Portion ◽  
Hek 293 ◽  
Assembly Factors ◽  
Regulated Gene Expression

Abstract We have identified a MOZ-TIF2 (MT2) fusion gene containing the N-terminal portion of MOZ and the C-terminal portion of TIF2 from a patient with acute leukemia with a chromosome 8 translocation. We report here that MOZ portion of MOZ-TIF2 associates with chromatin assembly factors, CAF1 (chromatin assembly factor 1) and ASF1 (anti-silencing factor 1) in mammalian cells. Both proteins not only bring histones to newly synthesized DNA to create chromatin structure in the replication of chromosomes and DNA damage-repair processes but also contribute to regulation of global gene expression. Using the MOZ portion of MT2 as the bait in the yeast two hybrid system, we found that the MOZ portion interacted with CAF1A and Asf1b. The interactions were further verified with GST-pull down experiments. Interestingly, co-immunoprecipitation with whole cell extracts from HEK 293 cells transiently transfected with GFP fusions of MOZ, MT2, and TIF2 showed that only MOZ strongly co-precipitated with CAF1A while MT2 only weakly co-precipitated. In contrast to CAF1A, MT2 showed a 3-fold stronger binding to Asf1b than wild type MOZ in pull-down experiments using S-tagged Asf1b and EGFP-fusions of MOZ, MT2, and TIF2. Further analysis of the domains within the MOZ portion of MT2 responsible for the interaction of CAF1A and Asf1b with MT2 indicated that the binding of CAF1A predominately depended on the PHD domain of MOZ and amino acids176–327 of CAF1A. The MYST domain of MOZ was responsible for the binding of the MOZ portion of MT2 to Asf1b. To further verify the differential binding of MOZ and MT2 to CAF1A and Asf1b, we observed the co-localization of transiently expressed EGFP-MOZ and EGFP-MT2 with DsRed-CAF1A in HEK 293 and Hela cells. In the merged images the MOZ co-localization with CAF-1A was stronger than the colocalization of MT2 with CAF1A and MT2 colocalization with Asf1b was stronger than MOZ colocalization with Asf1b. The co-localization of MOZ and MT2 with CAF1A with Asf1b was seen both in interphase and metaphase of the cell cycle. During the interphase, the co-localizations appeared with chromatin DNA and during metaphase the co-localizations were separated from chromatin DNA. The later phenomenon was further demonstrated with G2/M phase reagent, nocodozole. These results suggest a differential function of MT2 interacting with two chromatin assembly factors compared to wild-type MOZ. In view of the regulation of global gene expression by CAF1A and Asf1b, we examined the gene expression profile in U937 cells stably expressing MT2. Compared to the expression profile of control cells stably transfected with pcDNA3 vector alone, MT2 caused a > 5-fold change in expression 181 genes (104 genes increasing and 77 genes decreasing expression) (p = 0.05). While overexpression of wild type MOZ also altered gene expression (>5-fold increase in 479 genes and >5-fold decrease in 118 genes) a differential gene expression signature was seen between MOZ and MT2. MT2 altered expression of 57% of the 597 MOZ regulated genes. Included in the genes that were either up or down-regulated by MT2 were genes involved in multiple cell functions such as signal transduction, cell response to stimulus, and development. These results suggest that MT2 fusion may interfere with the function of wild type MOZ in global gene expression during the development of myeloid cells by differential interaction with chromatin chaperon proteins and the altered global gene expression profile could contribute to leukemogenesis.

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