کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
1949266 1537739 2013 9 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Metabolic adaptation allows Amacr-deficient mice to remain symptom-free despite low levels of mature bile acids
موضوعات مرتبط
علوم زیستی و بیوفناوری بیوشیمی، ژنتیک و زیست شناسی مولکولی زیست شیمی
پیش نمایش صفحه اول مقاله
Metabolic adaptation allows Amacr-deficient mice to remain symptom-free despite low levels of mature bile acids
چکیده انگلیسی


• Amacr−/− mice are physiologically asymptomatic under standard laboratory diet.
• Hepatic sterol synthesis in Amacr−/− mice is increased by 500%.
• Body cholesterol pool remains unchanged due to increased cholesterol excretion.
• Changes in lipoprotein profiles are mainly due to the decreased PLTP activity.
• Amacr−/− mice show how cholesterol metabolism is adjusted in lack of bile acids.

Bile acids play multiple roles in the physiology of vertebrates; they facilitate lipid absorption, serve as signaling molecules to control carbohydrate and lipid metabolism, and provide a disposal route for cholesterol. Unexpectedly, the α-methylacyl-CoA racemase (Amacr) deficient mice, which are unable to complete the peroxisomal cleavage of C27-precursors to the mature C24-bile acids, are physiologically asymptomatic when maintained on a standard laboratory diet. The aim of this study was to uncover the underlying adaptive mechanism with special reference to cholesterol and bile acid metabolism that allows these mice to have a normal life span. Intestinal cholesterol absorption in Amacr −/− mice is decreased resulting in a 2-fold increase in daily cholesterol excretion. Also fecal excretion of bile acids (mainly C27-sterols) is enhanced 3-fold. However, the body cholesterol pool remains unchanged, although Amacr-deficiency accelerates hepatic sterol synthesis 5-fold. Changes in lipoprotein profiles are mainly due to decreased phospholipid transfer protein activity. Thus Amacr-deficient mice provide a unique example of metabolic regulation, which allows them to have a normal lifespan in spite of the disruption of a major metabolic pathway. This metabolic adjustment can be mainly explained by setting cholesterol and bile acid metabolism to a new balanced level in the Amacr-deficient mouse.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biology of Lipids - Volume 1831, Issue 8, August 2013, Pages 1335–1343
نویسندگان
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