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Biochim Biophys Acta. 2016 May;1861(5):410-8. doi: 10.1016/j.bbalip.2016.02.018. Epub 2016 Feb 24.

Adipose tissue deficiency results in severe hyperlipidemia and atherosclerosis in the low-density lipoprotein receptor knockout mice.

Author information

1
Department of Cardiology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, China; Institute of Cardiovascular Sciences, Peking University Health Science Center, Beijing 100191, China.
2
Institute of Cardiovascular Sciences, Peking University Health Science Center, Beijing 100191, China.
3
School of Biotechnology and Biomolecular Sciences, the University of New South Wales, Sydney, NSW 2052, Australia.
4
Department of Cardiology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, China.
5
Institute of Cardiovascular Sciences, Peking University Health Science Center, Beijing 100191, China. Electronic address: georgeliu@bjmu.edu.cn.
6
Department of Cardiology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, China; School of Biotechnology and Biomolecular Sciences, the University of New South Wales, Sydney, NSW 2052, Australia. Electronic address: h.rob.yang@unsw.edu.au.

Abstract

Adipose tissue can store over 50% of whole-body cholesterol; however, the physiological role of adipose tissue in cholesterol metabolism and atherogenesis has not been directly assessed. Here, we examined lipoprotein metabolism and atherogenesis in a unique mouse model of severe lipodystrophy: the Seipin(-/-) mice, and also in mice deficient in both low-density lipoprotein receptor (Ldlr) and Seipin: the Ldlr(-/-)Seipin(-/-) mice. Plasma cholesterol was moderately increased in the Seipin(-/-) mice when fed an atherogenic diet. Strikingly, plasma cholesterol reached ~6000 mg/dl in the Seipin(-/-)Ldlr(-/-) mice on an atherogenic diet, as compared to ~1000 mg/dl in the Ldlr(-/-) mice on the same diet. The Seipin(-/-)Ldlr(-/-) mice also developed spontaneous atherosclerosis on chow diet and severe atherosclerosis on an atherogenic diet. Rosiglitazone treatment significantly reduced the hypercholesterolemia of the Seipin(-/-)Ldlr(-/-) mice, and also alleviated the severity of atherosclerosis. Our results provide direct evidence, for the first time, that the adipose tissue plays a critical role in the clearance of plasma cholesterol. Our results also reveal a previously unappreciated strong link between adipose tissue and LDLR in plasma cholesterol metabolism.

KEYWORDS:

Adipose tissue; Cholesterol; Hypercholesterolemia; Lipodystrophy; Seipin

PMID:
26921684
DOI:
10.1016/j.bbalip.2016.02.018
[Indexed for MEDLINE]

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