Beta(3)-adrenergic signaling acutely down regulates adipose triglyceride lipase in brown adipocytes.
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.
Department of Animal Sciences, The Ohio State University, Columbus, OH 43210, USA.
Jeffrey A
JA
Deiuliis
Li-Fen
LF
Liu
Martha A
MA
Belury
Jong S
JS
Rim
Sangsu
S
Shin
Kichoon
K
Lee
D052437:Adipocytes, Brown / Q000201:enzymology* / Q000378:metabolism; D002001:Adipose Tissue, Brown / Q000201:enzymology / Q000378:metabolism; D052436:Adipose Tissue, White / Q000378:metabolism; D000818:Animals; D004149:Dioxoles; D015536:Down-Regulation; D008049:Lipase / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D019869:Phosphatidylinositol 3-Kinases / Q000235:genetics / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000235:genetics / Q000378:metabolism; D022702:Receptors, Adrenergic, beta-3 / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction
D004149:Dioxoles; D022702:Receptors, Adrenergic, beta-3; C076126:disodium (R,R)-5-(2-((2-(3-chlorophenyl)-2-hydroxyethyl)-amino)propyl)-1,3-benzodioxole-2,3-dicarboxylate; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt; D008049:Lipase