title: Leptin deficiency suppresses progression of atherosclerosis in apoE-deficient mice.
abstract: 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.
authors.affiliation: 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.
authors.forename: Tsuyoshi
authors.initials: T
authors.lastname: Chiba
authors.affiliation: Vascular Medicine and Geriatrics, Department of Medicine, Tokyo Medical and Dental University, Graduate School, Yushima 1-5-45, Bunkyo-ku, Tokyo 113-8519, Japan.
authors.forename: Shohei
authors.initials: S
authors.lastname: Shinozaki
authors.affiliation: Vascular Medicine and Geriatrics, Department of Medicine, Tokyo Medical and Dental University, Graduate School, Yushima 1-5-45, Bunkyo-ku, Tokyo 113-8519, Japan.
authors.forename: Toru
authors.initials: T
authors.lastname: Nakazawa
authors.affiliation: Vascular Medicine and Geriatrics, Department of Medicine, Tokyo Medical and Dental University, Graduate School, Yushima 1-5-45, Bunkyo-ku, Tokyo 113-8519, Japan.
authors.forename: Akio
authors.initials: A
authors.lastname: Kawakami
authors.affiliation: Vascular Medicine and Geriatrics, Department of Medicine, Tokyo Medical and Dental University, Graduate School, Yushima 1-5-45, Bunkyo-ku, Tokyo 113-8519, Japan.
authors.forename: Masumi
authors.initials: M
authors.lastname: Ai
authors.affiliation: Vascular Medicine and Geriatrics, Department of Medicine, Tokyo Medical and Dental University, Graduate School, Yushima 1-5-45, Bunkyo-ku, Tokyo 113-8519, Japan.
authors.forename: Eiji
authors.initials: E
authors.lastname: Kaneko
authors.affiliation: Department of Pathology, Tokyo Medical and Dental University, Graduate School, Yushima 1-5-45, Bunkyo-ku, Tokyo 113-8519, Japan.
authors.forename: Masanobu
authors.initials: M
authors.lastname: Kitagawa
authors.affiliation: Ochanomizu University, Institute of Environmental Science for Human Life, Ohtsuka 2-1-1, Bunkyo-ku, Tokyo 112-8610, Japan.
authors.forename: Kazuo
authors.initials: K
authors.lastname: Kondo
authors.affiliation: Division of Metabolism, Endocrinology & Nutrition, Department of Medicine, University of Washington, Seattle, WA 98195-6426, USA.
authors.forename: Alan
authors.initials: A
authors.lastname: Chait
authors.affiliation: 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.
authors.forename: Kentaro
authors.initials: K
authors.lastname: Shimokado
mesh_terms: 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*
chemical_list: D001057:Apolipoproteins E; D020738:Leptin