Increased energy expenditure, dietary fat wasting, and resistance to diet-induced obesity in mice lacking renin.
An overactive renin-angiotensin system is associated with obesity and the metabolic syndrome. However, the mechanisms behind it are unclear. Cleaving angiotensinogen to angiotensin I by renin is a rate-limiting step of angiotensin II production, but renin is suggested to have angiotensin-independent effects. We generated mice lacking renin (Ren1c) using embryonic stem cells from C57BL/6 mice, a strain prone to diet-induced obesity. Ren1c(-/-) mice are lean, insulin sensitive, and resistant to diet-induced obesity without changes in food intake and physical activity. The lean phenotype is likely due to a higher metabolic rate and gastrointestinal loss of dietary fat. Most of the metabolic changes in Ren1c(-/-) mice were reversed by angiotensin II administration. These results support a role for angiotensin II in the pathogenesis of diet-induced obesity and insulin resistance.
Takahashi
Nobuyuki
N
Department of Pathology and Laboratory Medicine, The University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA. ntakaha@med.unc.edu
Li
Feng
F
Hua
Kunjie
K
Deng
Jianbei
J
Wang
Chih-Hong
CH
Bowers
Robert R
RR
Bartness
Timothy J
TJ
Kim
Hyung-Suk
HS
Harp
Joyce B
JB
D000273:Adipose Tissue / Q000378:metabolism; D000804:Angiotensin II / Q000172:deficiency / Q000494:pharmacology; D000818:Animals; D001481:Basal Metabolism; D051048:Diacylglycerol O-Acyltransferase / Q000235:genetics / Q000378:metabolism; D004041:Dietary Fats / Q000008:administration & dosage / Q000378:metabolism*; D004734:Energy Metabolism; D007328:Insulin / Q000494:pharmacology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009765:Obesity / Q000235:genetics / Q000378:metabolism / Q000517:prevention & control*; D010641:Phenotype; D012083:Renin / Q000172:deficiency* / Q000235:genetics; D013851:Thinness / Q000235:genetics / Q000378:metabolism
D004041:Dietary Fats; D007328:Insulin; D000804:Angiotensin II; C494882:Dgat1 protein, mouse; D051048:Diacylglycerol O-Acyltransferase; D012083:Renin