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Effects of 5‐lipoxygenase deficiency on adiposity, adrenal and beta cell functions, and bone density
Author(s) -
Mehrabian Margarete,
Maedler Kathrin,
Allayee Hooman,
Zhou Ziaqiang,
Stockton Jirina,
Lusis Aldons Jake
Publication year - 2006
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.20.5.a957-c
Subject(s) - endocrinology , dyslipidemia , medicine , insulin resistance , metabolic syndrome , inflammation , adipokine , diabetes mellitus , proinflammatory cytokine , arachidonate 5 lipoxygenase , arachidonic acid , biology , enzyme , biochemistry
5‐lipoxygenase (5LO) is the key enzyme for the conversion of arachidonic acid to leukotrienes. Recent genetic evidence supports the notion that this pathway contributes to atherosclerosis, aortic aneurysms, and coronary heart disease in mice and humans. Mice deficient for 5LO or leukotriene receptors were shown to be less susceptible to aortic lesion formation and aneurysms. Four major human studies have confirmed these findings. Related conditions of obesity, dyslipidemia, and insulin resistance are known risk factors for CHD and essential components of metabolic syndrome. In the present study, we have explored the possibility that 5LO deficiency may also affect these cardiovascular risk factors using a 5LO knockout mouse model. 5LO null mice have higher VLDL/LDL levels, exhibit significantly increased adiposity, disproportionately increased leptin levels, beta cell hypertrophy and impaired insulin secretion. The mice also exhibited dramatic decreases in the levels of adrenal lipids and significantly increased bone density. Through this analysis, we have found that a number of metabolic processes considered to be atherosclerotic risk factors are regulated, in part by 5LO. Our results are significant in understanding the chronic inflammation associated with obesity and thought to be important in diabetes and cardiovascular disease. AHA 0355031Y; NIH PO1 HL30568; RO1 HL079353