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Increased diet-induced fatty streak formation in female mice with deficiency of liver-derived insulin-like growth factor-I.

Journal article
Authors Johan Svensson
Klara Sjögren
Malin Levin
Jan Borén
Åsa Tivesten
Claes Ohlsson
Published in Endocrine
Volume 52
Issue 3
Pages 550-560
ISSN 1559-0100
Publication year 2016
Published at Wallenberg Laboratory
Centre for Bone and Arthritis Research
Institute of Medicine, Department of Internal Medicine and Clinical Nutrition
Institute of Medicine, Department of Molecular and Clinical Medicine
Pages 550-560
Language en
Links dx.doi.org/10.1007/s12020-015-0809-...
Subject categories Endocrinology

Abstract

The role of endocrine IGF-I for atherosclerosis is unclear. We determined the importance of circulating, liver-derived IGF-I for fatty streak formation in mice. Mice with adult, liver-specific IGF-I inactivation (LI-IGF-I(-/-) mice, serum IGF-I reduced by approximately 80 %) and control mice received an atherogenic (modified Paigen) diet between 6 and 12 months of age. At study end, Oil Red O staining of aortic root cryosections showed increased fatty streak area and lipid deposition in female but not in male LI-IGF-I(-/-) mice compared to controls. Mac-2 staining of aortic root and measurements of CD68 mRNA level in femoral artery revealed increased macrophage accumulation in proportion to the increased fatty streak area in female LI-IGF-I(-/-) mice. Moreover, female LI-IGF-I(-/-) mice displayed increased serum cholesterol and interleukin-6 as well as increased vascular cell-adhesion molecule 1 (VCAM1) mRNA levels in the femoral artery and elevated VCAM1 protein expression in the aortic root. Thus, increased diet-induced fatty streak formation in female LI-IGF-I(-/-) mice was associated with increased serum cholesterol and signs of systemic inflammation, endothelial activation, lipid deposition, and macrophage infiltration in the vascular wall.

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