Your email was sent successfully. Check your inbox.

An error occurred while sending the email. Please try again.

Proceed reservation?

Export
  • 1
    Keywords: CELLS ; EXPRESSION ; proliferation ; CELL ; Germany ; MODEL ; MODELS ; PATHWAY ; PATHWAYS ; GENE ; GENE-EXPRESSION ; METABOLISM ; TISSUE ; MICE ; ACTIVATION ; FAMILY ; INDUCTION ; cytokines ; TARGET ; IDENTIFICATION ; AMPLIFICATION ; PATTERNS ; gene expression ; SUBUNIT ; DESIGN ; resistance ; ENERGY ; STRESS ; OBESITY ; diabetes ; DIET ; GLUCOSE ; REGULATOR ; inflammation ; insulin ; signaling ; INTEGRATION ; CYTOKINE ; PATTERN ; GENE FAMILY ; INSULIN-RESISTANCE ; chronic inflammation ; EXPRESSION PATTERNS ; HOMEOSTASIS ; PROINFLAMMATORY CYTOKINES ; MAINTENANCE ; FAMILY-MEMBERS ; RATIONALE ; COACTIVATOR ; hypothesis ; Type ; EXPRESSION PATTERN ; Adipocyte ; C/EBP-BETA ; LIPID-METABOLISM ; MAMMALIAN TRIBBLES
    Abstract: OBJECTIVE-Based on its role as an energy storage compartment and endocrine organ, white adipose tissue (WAT) fulfills a critical function in the maintenance of whole-body energy homeostasis. Indeed, WAT dysfunction is connected to obesity-related type 2 diabetes triggered at least partly by an inflammatory response in adipocytes The pseudokinase tribbles (TRB) 3 has been identified by us and others as a critical regulator of hepatic glucose homeostasis in type 2 diabetes and WAT lipid homeostasis Therefore, this study aimed to test the hypothesis that the TRB gene family fulfills broader functions in the Integration of metabolic and inflammatory pathways in various tissues. RESEARCH DESIGN AND METHODS-To determine the role of TRB family members for WAT function, we profiled the expression patterns of TRB13 under healthy and metabolic stress conditions The differentially expressed TRB1 was functionally characterized in loss-of-function animal and primary adipocyte models. RESULTS-Here, we show that the expression of TRB1 was specifically upregulated during acute and chronic inflammation in WAT of mice. Deficiency of TRB1 was found to impair cytokine gene expression in white adipocytes and to protect against high-fat diet induced obesity. In adipocytes, TRB1 served as a nuclear transcriptional coactivator for the nuclear factor kappa B subunit RelA, thereby promoting the induction of proinflammatory cytokines in these cells. CONCLUSIONS-As inflammation is typically seen in sepsis, insulin resistance, and obesity-related type 2 diabetes, the dual role of TRB1 as both a target and a (co) activator of inflammatory signaling might provide a molecular rationale for the amplification of proinflammatory responses in WAT in these subjects. Diabetes 59:1991-2000, 2010
    Type of Publication: Journal article published
    PubMed ID: 20522600
    Signatur Availability
    BibTip Others were also interested in ...
  • 2
    Keywords: INHIBITION ; MODEL ; GENE ; GENE-EXPRESSION ; METABOLISM ; MICE ; OBESITY ; inflammation ; MOUSE MODELS ; COACTIVATOR PGC-1 ; INSULIN-RESISTANCE ; TECHNOLOGY ; NUCLEAR RECEPTORS ; Hepatic expression of transcriptional cofactor TBL1 is impaired in fatty livers ; Hepatic deficiency in TBL1 promotes liver steatosis and hypertriglyceridemia ; Hepatic TBL1 acts in concert with TBLR1 and nuclear receptor PPARα ; NONALCOHOLIC FATTY LIVER ; STIMULATED LIPOPROTEIN RECEPTOR
    Abstract: The aberrant accumulation of lipids in the liver ("fatty liver") is tightly associated with several components of the metabolic syndrome, including type 2 diabetes, coronary heart disease, and atherosclerosis. Here we show that the impaired hepatic expression of transcriptional cofactor transducin beta-like (TBL) 1 represents a common feature of mono- and multigenic fatty liver mouse models. Indeed, the liver-specific ablation of TBL1 gene expression in healthy mice promoted hypertriglyceridemia and hepatic steatosis under both normal and high-fat dietary conditions. TBL1 deficiency resulted in inhibition of fatty acid oxidation due to impaired functional cooperation with its heterodimerization partner TBL-related (TBLR) 1 and the nuclear receptor peroxisome proliferator-activated receptor (PPAR) alpha. As TBL1 expression levels were found to also inversely correlate with liver fat content in human patients, the lack of hepatic TBL1/TBLR1 cofactor activity may represent a molecular rationale for hepatic steatosis in subjects with obesity and the metabolic syndrome.
    Type of Publication: Journal article published
    PubMed ID: 21459324
    Signatur Availability
    BibTip Others were also interested in ...
Close ⊗
This website uses cookies and the analysis tool Matomo. More information can be found here...