Document Detail


Beta(3)-adrenergic signaling acutely down regulates adipose triglyceride lipase in brown adipocytes.
MedLine Citation:
PMID:  20509000     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Mice exposed to cold rely upon brown adipose tissue (BAT)-mediated nonshivering thermogenesis to generate body heat using dietary glucose and lipids from the liver and white adipose tissue. In this report, we investigate how cold exposure affects the PI3 K/Akt signaling cascade and the expression of genes involved in lipid metabolism and trafficking in BAT. Cold exposure at an early time point led to the activation of the PI3 K/Akt, insulin-like signaling cascade followed by a transient decrease in adipose triglyceride lipase (ATGL) gene and protein expression in BAT. To further investigate how cold exposure-induced signaling altered ATGL expression, cultured primary brown adipocytes were treated with the beta(3)-adrenergic receptor (beta(3)AR) agonist CL 316,243 (CL) resulting in activation of PI3 K/Akt, ERK 1/2, and p38 signaling pathways and significantly decreased ATGL protein levels. ATGL protein levels decreased significantly 30 min post CL treatment suggesting protein degradation. Inhibition of PKA signaling by H89 rescued ATGL levels. The effects of PKA signaling on ATGL were shown to be independent of relevant pathways downstream of PKA such as PI3 K/Akt, ERK 1/2, and p38. However, CL treatment in 3T3-L1 adipocytes did not decrease ATGL protein and mRNA expression, suggesting a distinct response in WAT to beta3-adrenergic agonism. Transitory effects, possibly attributed to acute Akt activation during the early recruitment phase, were noted as well as stable changes in gene expression which may be attributed to beta3-adrenergic signaling in BAT.
Authors:
Jeffrey A Deiuliis; Li-Fen Liu; Martha A Belury; Jong S Rim; Sangsu Shin; Kichoon Lee
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2010-05-28
Journal Detail:
Title:  Lipids     Volume:  45     ISSN:  1558-9307     ISO Abbreviation:  Lipids     Publication Date:  2010 Jun 
Date Detail:
Created Date:  2010-06-17     Completed Date:  2010-10-18     Revised Date:  2013-06-03    
Medline Journal Info:
Nlm Unique ID:  0060450     Medline TA:  Lipids     Country:  Germany    
Other Details:
Languages:  eng     Pagination:  479-89     Citation Subset:  IM    
Affiliation:
Department of Animal Sciences, The Ohio State University, Columbus, OH 43210, USA.
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MeSH Terms
Descriptor/Qualifier:
Adipocytes, Brown / enzymology*,  metabolism
Adipose Tissue, Brown / enzymology,  metabolism
Adipose Tissue, White / metabolism
Animals
Dioxoles
Down-Regulation*
Lipase / genetics,  metabolism*
Mice
Mice, Inbred C57BL
Phosphatidylinositol 3-Kinases / genetics,  metabolism
Proto-Oncogene Proteins c-akt / genetics,  metabolism
Receptors, Adrenergic, beta-3 / genetics,  metabolism*
Signal Transduction*
Grant Support
ID/Acronym/Agency:
UL1 RR025755/RR/NCRR NIH HHS
Chemical
Reg. No./Substance:
0/Dioxoles; 0/Receptors, Adrenergic, beta-3; 138908-40-4/disodium (R,R)-5-(2-((2-(3-chlorophenyl)-2-hydroxyethyl)-amino)propyl)-1,3-benzodioxole-2,3-dicarboxylate; EC 2.7.1.-/Phosphatidylinositol 3-Kinases; EC 2.7.11.1/Proto-Oncogene Proteins c-akt; EC 3.1.1.3/Lipase

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