Arginine-vasopressin directly promotes a thermogenic and pro-inflammatory adipokine expression profile in brown adipocytes.
Arginine-vasopressin (AVP) - via activation of the hypothalamic-pituitary-adrenal (HPA) axis - may play a role in the regulation of energy homeostasis and related cardiovascular complications. Brown adipose tissue (BAT) - via dissipation of energy in the form of heat - contributes to whole body energy balance. BAT expresses vasopressin receptors. We investigated direct effects of AVP on brown adipose endocrine and metabolic functions. UCP-1 protein expression in differentiated brown adipocytes was induced after acute exposure of adipocytes to AVP. This effect was time-dependent with a maximum increase after 8h. AVP also induced a time- and dose-dependent increase in p38 MAP kinase phosphorylation. Pharmacological inhibition of p38 MAP kinase with SB 202190 abolished the induction of UCP-1 protein expression. Furthermore, while acute AVP treatment enhanced mRNA expression of MCP-1 and IL-6, adiponectin mRNA expression was reduced. Yet, on the level of intracellular glucose uptake, there was no AVP-induced change of adipose insulin-induced glucose uptake. Finally, there was no difference in lipid accumulation between control and AVP-treated cells. Taken together, our data demonstrate direct effects of AVP on thermogenic, inflammatory, and glucoregulatory gene expression in brown adipocytes, thus expanding the hitherto known spectrum of this neuropeptides's biological effects and suggesting a direct adipotropic role as a stress-promoting factor.
Küchler
Sebastian
S
Department of Internal Medicine, Federal Armed Forces Hospital, Ulm, Germany.
Perwitz
Nina
N
Schick
Rafael Reinhold
RR
Klein
Johannes
J
Westphal
Sören
S
D052437:Adipocytes, Brown / Q000187:drug effects* / Q000378:metabolism*; D054392:Adipokines / Q000378:metabolism*; D052242:Adiponectin / Q000235:genetics; D000818:Animals; D001127:Arginine Vasopressin / Q000494:pharmacology*; D002478:Cells, Cultured; D018932:Chemokine CCL2 / Q000235:genetics; D004791:Enzyme Inhibitors / Q000494:pharmacology; D007030:Hypothalamo-Hypophyseal System / Q000187:drug effects / Q000378:metabolism; D007093:Imidazoles / Q000494:pharmacology; D015151:Immunoblotting; D007328:Insulin / Q000494:pharmacology; D015850:Interleukin-6 / Q000235:genetics; D007473:Ion Channels / Q000235:genetics; D051379:Mice; D024101:Mitochondrial Proteins / Q000235:genetics; D010766:Phosphorylation / Q000187:drug effects; D010913:Pituitary-Adrenal System / Q000187:drug effects / Q000378:metabolism; D011725:Pyridines / Q000494:pharmacology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D000071256:Uncoupling Protein 1; D048051:p38 Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism
D054392:Adipokines; D052242:Adiponectin; C491768:Ccl2 protein, mouse; D018932:Chemokine CCL2; D004791:Enzyme Inhibitors; D007093:Imidazoles; D007328:Insulin; D015850:Interleukin-6; D007473:Ion Channels; D024101:Mitochondrial Proteins; D011725:Pyridines; C000604372:Ucp1 protein, mouse; D000071256:Uncoupling Protein 1; D001127:Arginine Vasopressin; D048051:p38 Mitogen-Activated Protein Kinases; C090942:4-(4-fluorophenyl)-2-(4-hydroxyphenyl)-5-(4-pyridyl)imidazole