The adipose-tissue renin-angiotensin-aldosterone system: role in the metabolic syndrome?
Overfeeding of rodents leads to increased local formation of angiotensin II due to increased secretion of angiotensinogen from adipocytes. Whereas angiotensin II promotes adipocyte growth and preadipocyte recruitment, increased secretion of angiotensinogen from adipocytes also directly contributes to the close relationship between adipose-tissue mass and blood pressure in mice. In contrast, angiotensin II acts as an antiadipogenic substance in human adipose tissue, and the total increase in adipose-tissue mass may be more important in determining human plasma angiotensinogen levels than changes within the single adipocyte. However, as increased local formation of angiotensin II in adipose tissue may be increased especially in obese hypertensive subjects, a contribution of the adipose-tissue renin-angiotensin system to the development of insulin resistance and hypertension is conceivable in humans, but not yet proven. Insulin resistance may be aggravated by the inhibition of preadipocyte recruitment, which results in the redistribution of triglycerides to the liver and skeletal muscle, and blood pressure may be influenced by local formation of angiotensin II in perivascular adipose tissue. Thus, although the mechanisms are still speculative, the beneficial effects of ACE-inhibition and angiotensin-receptor blockade on the development of type 2 diabetes in large clinical trials suggest a pathophysiological role of the adipose-tissue renin-angiotensin system in the metabolic syndrome.
Engeli
Stefan
S
HELIOS Klinikum Berlin, Franz Volhard Clinic--Charité, Department of Nephrology and Hypertension, Humboldt University of Berlin, Wiltberg Strasse 50, Berlin 13125, Germany. engeli@fvk.charite-buch.de
Schling
Petra
P
Gorzelniak
Kerstin
K
Boschmann
Michael
M
Janke
Jürgen
J
Ailhaud
Gérard
G
Teboul
Michèle
M
Massiéra
Florence
F
Sharma
Arya M
AM
D017667:Adipocytes / Q000378:metabolism; D002001:Adipose Tissue, Brown / Q000378:metabolism; D000804:Angiotensin II / Q000378:metabolism*; D000808:Angiotensinogen / Q000378:metabolism*; D000818:Animals; D006801:Humans; D006973:Hypertension / Q000503:physiopathology; D007333:Insulin Resistance / Q000502:physiology; D024821:Metabolic Syndrome / Q000209:etiology / Q000378:metabolism*; D051379:Mice; D009765:Obesity / Q000503:physiopathology; D007703:Peptidyl-Dipeptidase A / Q000378:metabolism; D051381:Rats; D012083:Renin / Q000378:metabolism; D012084:Renin-Angiotensin System / Q000502:physiology*; D022722:Thermogenesis / Q000502:physiology
D000808:Angiotensinogen; D000804:Angiotensin II; D007703:Peptidyl-Dipeptidase A; D012083:Renin