Leptin deficiency suppresses progression of atherosclerosis in apoE-deficient mice.
Both experimental and epidemiological studies suggest that leptin is one of the molecules responsible for accelerated atherosclerosis in obese humans. To confirm the notion, we studied whether leptin accelerates atherosclerosis in apoE(-/-) mice. Leptin deficient hyperlipidemic mice (ob/ob;apoE(-/-) mice) developed significantly less atherosclerosis than apoE(-/-) mice, when fed an atherogenic diet for 16 weeks from 8 weeks of age. Histological analysis revealed that most of the atherosclerotic lesions in ob/ob;apoE(-/-) mice remained as fatty streaks, while those in apoE(-/-) mice were mainly fibrous plaques. The decrease in atherosclerosis was not due to changes in the serum levels of cholesterol, TNF-alpha, or adiponectin. Exogenous leptin significantly increased atherosclerotic areas in apoE(-/-) mice, even though it decreased food intake and body weight. Our findings support the notion that leptin accelerates atherosclerosis.
Chiba
Tsuyoshi
T
Vascular Medicine and Geriatrics, Department of Medicine, Tokyo Medical and Dental University, Graduate School, Yushima 1-5-45, Bunkyo-ku, Tokyo 113-8519, Japan; Ochanomizu University, Institute of Environmental Science for Human Life, Ohtsuka 2-1-1, Bunkyo-ku, Tokyo 112-8610, Japan.
Shinozaki
Shohei
S
Vascular Medicine and Geriatrics, Department of Medicine, Tokyo Medical and Dental University, Graduate School, Yushima 1-5-45, Bunkyo-ku, Tokyo 113-8519, Japan.
Nakazawa
Toru
T
Vascular Medicine and Geriatrics, Department of Medicine, Tokyo Medical and Dental University, Graduate School, Yushima 1-5-45, Bunkyo-ku, Tokyo 113-8519, Japan.
Kawakami
Akio
A
Vascular Medicine and Geriatrics, Department of Medicine, Tokyo Medical and Dental University, Graduate School, Yushima 1-5-45, Bunkyo-ku, Tokyo 113-8519, Japan.
Ai
Masumi
M
Vascular Medicine and Geriatrics, Department of Medicine, Tokyo Medical and Dental University, Graduate School, Yushima 1-5-45, Bunkyo-ku, Tokyo 113-8519, Japan.
Kaneko
Eiji
E
Vascular Medicine and Geriatrics, Department of Medicine, Tokyo Medical and Dental University, Graduate School, Yushima 1-5-45, Bunkyo-ku, Tokyo 113-8519, Japan.
Kitagawa
Masanobu
M
Department of Pathology, Tokyo Medical and Dental University, Graduate School, Yushima 1-5-45, Bunkyo-ku, Tokyo 113-8519, Japan.
Kondo
Kazuo
K
Ochanomizu University, Institute of Environmental Science for Human Life, Ohtsuka 2-1-1, Bunkyo-ku, Tokyo 112-8610, Japan.
Chait
Alan
A
Division of Metabolism, Endocrinology & Nutrition, Department of Medicine, University of Washington, Seattle, WA 98195-6426, USA.
Shimokado
Kentaro
K
Vascular Medicine and Geriatrics, Department of Medicine, Tokyo Medical and Dental University, Graduate School, Yushima 1-5-45, Bunkyo-ku, Tokyo 113-8519, Japan. Electronic address: k.shimoka.vasc@tmd.ac.jp.
D000818:Animals; D001057:Apolipoproteins E / Q000235:genetics*; D050197:Atherosclerosis / Q000235:genetics / Q000473:pathology / Q000503:physiopathology*; D004036:Diet, Atherogenic; D004195:Disease Models, Animal; D020738:Leptin / Q000172:deficiency* / Q000502:physiology*; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D009765:Obesity / Q000503:physiopathology*
D001057:Apolipoproteins E; D020738:Leptin