Angiotensin II promotes leptin production in cultured human fat cells by an ERK1/2-dependent pathway.
OBJECTIVE
The fat cell hormone leptin is known to be implicated in the pathogenesis of hypertension and cardiovascular disease. Here we tested whether angiotensin (Ang) II is involved in the control of leptin release from human adipocytes.


METHODS
Leptin secretion was assessed from in vitro differentiated human adipocytes by radioimmunoassay. Western blot experiments were used to test for the signaling pathway activated by Ang II.


RESULTS
Ang II increased leptin secretion into the culture medium in a dose- and time-dependent fashion. At 10(-5) M Ang II, the leptin concentration in the medium was increased at 24 hours by 500+/-222% compared with control cultures (p<0.05). This effect was also seen at the mRNA level. Similar effects were seen after exposure of fat cells to Ang III and Ang IV. Preincubation of fat cells with candesartan, an angiotensin II type 1 receptor antagonist, or the extracellular-signal-regulated kinases 1 and 2 inhibitor UO126 completely abolished the effect of Ang II on leptin production. The peroxisome proliferator-activated receptor-gamma agonist troglitazone modestly attenuated leptin release.


CONCLUSIONS
In conclusion, Ang II and its metabolites stimulated leptin production in human adipocytes. This effect is mediated through an extracellular-signal-regulated kinases 1 and 2-dependent pathway and includes the angiotensin II type 1 receptor subtype.
Skurk
Thomas
T
Else Kröner-Fresenius-Centre for Nutritional Medicine, Technical University Munich, Am Forum 5, 85350 Freising-Weihenstephan, Germany. nutritional-medicine@wzw.tum.de
van Harmelen
Vanessa
V
Blum
Werner F
WF
Hauner
Hans
H
D017667:Adipocytes / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism*; D000328:Adult; D000804:Angiotensin II / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D047228:Angiotensin II Type 1 Receptor Blockers / Q000494:pharmacology; D001562:Benzimidazoles / Q000494:pharmacology; D001713:Biphenyl Compounds; D015153:Blotting, Western; D002070:Butadienes / Q000494:pharmacology; D002478:Cells, Cultured; D002839:Chromans / Q000494:pharmacology; D004347:Drug Interactions; D048049:Extracellular Signal-Regulated MAP Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism; D005260:Female; D005343:Fibrinolytic Agents / Q000494:pharmacology; D006801:Humans; D020738:Leptin / Q000096:biosynthesis* / Q000378:metabolism; D020935:MAP Kinase Signaling System / Q000187:drug effects / Q000502:physiology*; D009570:Nitriles / Q000494:pharmacology; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D012333:RNA, Messenger / Q000737:chemistry / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013777:Tetrazoles / Q000494:pharmacology; D045162:Thiazolidinediones / Q000494:pharmacology; D000077288:Troglitazone
D047228:Angiotensin II Type 1 Receptor Blockers; D001562:Benzimidazoles; D001713:Biphenyl Compounds; D002070:Butadienes; D002839:Chromans; D005343:Fibrinolytic Agents; D020738:Leptin; D009570:Nitriles; D047428:Protein Kinase Inhibitors; D012333:RNA, Messenger; D013777:Tetrazoles; D045162:Thiazolidinediones; C113580:U 0126; D000804:Angiotensin II; D048049:Extracellular Signal-Regulated MAP Kinases; D000077288:Troglitazone; C081643:candesartan