PMID- 18310442
OWN - NLM
STAT- MEDLINE
DCOM- 20091001
LR  - 20210526
IS  - 1479-6805 (Electronic)
IS  - 0022-0795 (Linking)
VI  - 196
IP  - 3
DP  - 2008 Mar
TI  - Melanocortin crosstalk with adipose functions: ACTH directly induces insulin 
      resistance, promotes a pro-inflammatory adipokine profile and stimulates UCP-1 in 
      adipocytes.
PG  - 465-72
LID - 10.1677/JOE-07-0299 [doi]
AB  - The melanocortin (MC) system is a pivotal component of the 
      hypothalamo-pituitary-adrenal (HPA) stress axis and plays an important role in 
      the pathogenesis of obesity and the metabolic syndrome. Adipose dysfunction is 
      implicated in the pathogenesis of these disorders. We investigated direct ACTH 
      effects on adipose functions in immortalised murine white and brown adipocytes. 
      MC receptor types 2 and 5 were expressed at the mRNA and protein levels and were 
      strongly up-regulated during differentiation. Chronic ACTH stimulation did not 
      affect adipogenesis. Insulin-induced glucose uptake in white adipocytes was 
      acutely and transiently reduced by 45% upon ACTH treatment. Visfatin and 
      adiponectin gene expression was reduced by about 50% in response to ACTH, while 
      interleukin-6 (IL-6) and monocyte chemoattractant protein-1 (MCP-1) mRNA levels 
      were acutely up-regulated by 2100 and 60% respectively. Moreover, IL-6 secretion 
      was increased by 1450% within 4 h of ACTH treatment. In brown adipocytes, 
      stimulation with ACTH caused a 690% increase in uncoupling protein (UCP)-1 mRNA 
      levels within 8 h, followed by a 470% increase in UCP-1 protein concentrations 
      after 24 h. Consistently, p38 mitogen-activated protein kinase (MAPK) 
      phosphorylation was acutely increased by 1800% in response to ACTH stimulation, 
      and selective inhibition of p38 MAPK abolished the ACTH-mediated UCP-1 protein 
      increase. Taken together, ACTH acutely promotes an insulin-resistant, 
      pro-inflammatory state and transiently enhances energy combustion. In conditions 
      characterised by a dysregulation of the HPA stress axis such as the metabolic 
      syndrome, direct MC interaction with adipocytes may contribute to dysregulated 
      energy balance, insulin resistance and cardiometabolic complications.
FAU - Iwen, K Alexander H
AU  - Iwen KA
AD  - Department of Internal Medicine I, University of Lubeck, Ratzeburger Allee 160, 
      23538 Lubeck, Germany.
FAU - Senyaman, Oezge
AU  - Senyaman O
FAU - Schwartz, Arne
AU  - Schwartz A
FAU - Drenckhan, Maren
AU  - Drenckhan M
FAU - Meier, Britta
AU  - Meier B
FAU - Hadaschik, Dirk
AU  - Hadaschik D
FAU - Klein, Johannes
AU  - Klein J
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - England
TA  - J Endocrinol
JT  - The Journal of endocrinology
JID - 0375363
RN  - 0 (Adipokines)
RN  - 0 (Interleukin-6)
RN  - 0 (Ion Channels)
RN  - 0 (Mc3r protein, mouse)
RN  - 0 (Mitochondrial Proteins)
RN  - 0 (RNA, Messenger)
RN  - 0 (Receptor, Melanocortin, Type 1)
RN  - 0 (Receptor, Melanocortin, Type 2)
RN  - 0 (Receptor, Melanocortin, Type 3)
RN  - 0 (Receptor, Melanocortin, Type 4)
RN  - 0 (Receptors, Melanocortin)
RN  - 0 (Ucp1 protein, mouse)
RN  - 0 (Uncoupling Protein 1)
RN  - 0 (melanocortin 5 receptor)
RN  - 9002-60-2 (Adrenocorticotropic Hormone)
RN  - EC 2.7.11.24 (p38 Mitogen-Activated Protein Kinases)
SB  - IM
MH  - Adipocytes, Brown/cytology/immunology/*metabolism
MH  - Adipokines/immunology/metabolism
MH  - Adrenocorticotropic Hormone/*metabolism
MH  - Animals
MH  - Cell Differentiation/physiology
MH  - Cell Line, Transformed
MH  - Energy Metabolism/physiology
MH  - Inflammation/*metabolism
MH  - Insulin Resistance/*immunology
MH  - Interleukin-6/metabolism
MH  - Ion Channels/genetics/*metabolism
MH  - Mice
MH  - Mitochondrial Proteins/genetics/*metabolism
MH  - RNA, Messenger/metabolism
MH  - Receptor, Melanocortin, Type 1/genetics/metabolism
MH  - Receptor, Melanocortin, Type 2/genetics/metabolism
MH  - Receptor, Melanocortin, Type 3/genetics/metabolism
MH  - Receptor, Melanocortin, Type 4/genetics/metabolism
MH  - Receptors, Melanocortin/genetics/*metabolism
MH  - Uncoupling Protein 1
MH  - p38 Mitogen-Activated Protein Kinases/metabolism
EDAT- 2008/03/04 09:00
MHDA- 2009/10/02 06:00
CRDT- 2008/03/04 09:00
PHST- 2008/03/04 09:00 [pubmed]
PHST- 2009/10/02 06:00 [medline]
PHST- 2008/03/04 09:00 [entrez]
AID - 196/3/465 [pii]
AID - 10.1677/JOE-07-0299 [doi]
PST - ppublish
SO  - J Endocrinol. 2008 Mar;196(3):465-72. doi: 10.1677/JOE-07-0299.