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1.
Sci Rep ; 12(1): 15525, 2022 09 15.
Article in English | MEDLINE | ID: mdl-36109624

ABSTRACT

Cis-natural antisense transcripts (cis-NATs) are transcribed from the same genomic locus as their partner gene but from the opposite DNA strand and overlap with the partner gene transcript. Here, we developed a simple and convenient program termed CCIVR (comprehensive cis-NATs identifier via RNA-seq data) that comprehensively identifies all kinds of cis-NATs based on genome annotation with expression data obtained from RNA-seq. Using CCIVR with genome databases, we demonstrated total cis-NAT pairs from 11 model organisms. CCIVR analysis with RNA-seq data from parthenogenetic and androgenetic embryonic stem cells identified well-known imprinted cis-NAT pair, KCNQ1/KCNQ1OT1, ensuring the availability of CCIVR. Finally, CCIVR identified cis-NAT pairs that demonstrate inversely correlated expression upon TGFß stimulation including cis-NATs that functionally repress their partner genes by introducing epigenetic alteration in the promoters of partner genes. Thus, CCIVR facilitates the investigation of structural characteristics and functions of cis-NATs in numerous processes in various species.


Subject(s)
KCNQ1 Potassium Channel , RNA, Antisense , KCNQ1 Potassium Channel/genetics , Promoter Regions, Genetic , RNA, Antisense/genetics , RNA, Antisense/metabolism , Transforming Growth Factor beta/metabolism
2.
FEBS Lett ; 586(9): 1300-5, 2012 May 07.
Article in English | MEDLINE | ID: mdl-22465662

ABSTRACT

Ceramide kinase (CERK) is an enzyme that phosphorylates ceramide to produce ceramide 1-phosphate. Recently, evidence has emerged that CERK has a role in inflammatory signaling of immune cells. Since obesity is accompanied by chronic, low-grade inflammation, we examined whether CERK might be involved using CERK-null mice. We determined that CERK deficiency suppresses diet-induced increases in body weight, and improves glucose intolerance. Furthermore, we demonstrated that CERK deficiency attenuates MCP-1/CCR2 signaling in macrophages infiltrating the adipose tissue, resulting in the suppression of inflammation in adipocytes, which might otherwise lead to obesity and diabetes.


Subject(s)
Diet, High-Fat/adverse effects , Insulin Resistance , Obesity/enzymology , Obesity/etiology , Phosphotransferases (Alcohol Group Acceptor)/deficiency , Adipose Tissue/metabolism , Adipose Tissue/pathology , Animals , Body Weight , Chemokine CCL2/metabolism , Diabetes Mellitus/enzymology , Glucose Tolerance Test , Macrophages/immunology , Macrophages/metabolism , Mice , Obesity/metabolism , Obesity/pathology , Phosphotransferases (Alcohol Group Acceptor)/metabolism , Receptors, CCR2/metabolism , Signal Transduction
3.
J Biol Chem ; 286(32): 28544-55, 2011 Aug 12.
Article in English | MEDLINE | ID: mdl-21669879

ABSTRACT

Lipid microdomains or caveolae, small invaginations of plasma membrane, have emerged as important elements for lipid uptake and glucose homeostasis. Sphingomyelin (SM) is one of the major phospholipids of the lipid microdomains. In this study, we investigated the physiological function of sphingomyelin synthase 2 (SMS2) using SMS2 knock-out mice, and we found that SMS2 deficiency prevents high fat diet-induced obesity and insulin resistance. Interestingly, in the liver of SMS2 knock-out mice, large and mature lipid droplets were scarcely observed. Treatment with siRNA for SMS2 also decreased the large lipid droplets in HepG2 cells. Additionally, the siRNA of SMS2 decreased the accumulation of triglyceride in liver of leptin-deficient (ob/ob) mice, strongly suggesting that SMS2 is involved in lipid droplet formation. Furthermore, we found that SMS2 exists in lipid microdomains and partially associates with the fatty acid transporter CD36/FAT and with caveolin 1, a scaffolding protein of caveolae. Because CD36/FAT and caveolin 1 exist in lipid microdomains and are coordinately involved in lipid droplet formation, SMS2 is implicated in the modulation of the SM in lipid microdomains, resulting in the regulation of CD36/FAT and caveolae. Here, we established new cell lines, in which we can completely distinguish SMS2 activity from SMS1 activity, and we demonstrated that SMS2 could convert ceramide produced in the outer leaflet of the plasma membrane into SM. Our findings demonstrate the novel and dynamic regulation of lipid microdomains via conformational changes in lipids on the plasma membrane by SMS2, which is responsible for obesity and type 2 diabetes.


Subject(s)
Caveolae/metabolism , Diabetes Mellitus, Type 2/metabolism , Fatty Liver/metabolism , Obesity/metabolism , Sphingomyelins/metabolism , Animals , CD36 Antigens/genetics , CD36 Antigens/metabolism , Caveolae/pathology , Caveolin 1/genetics , Caveolin 1/metabolism , Ceramides/genetics , Ceramides/metabolism , Diabetes Mellitus, Type 2/chemically induced , Diabetes Mellitus, Type 2/genetics , Diabetes Mellitus, Type 2/pathology , Dietary Fats/adverse effects , Dietary Fats/pharmacology , Fatty Liver/chemically induced , Fatty Liver/genetics , Fatty Liver/pathology , Hep G2 Cells , Humans , Insulin Resistance/genetics , Insulin Resistance/radiation effects , Membrane Proteins/genetics , Membrane Proteins/metabolism , Mice , Mice, Knockout , Mice, Obese , Nerve Tissue Proteins/genetics , Nerve Tissue Proteins/metabolism , Obesity/chemically induced , Obesity/genetics , Obesity/pathology , Sphingomyelins/genetics , Transferases (Other Substituted Phosphate Groups)/genetics , Transferases (Other Substituted Phosphate Groups)/metabolism
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