| First Author | Selkälä EM | Year | 2013 |
| Journal | Biochim Biophys Acta | Volume | 1831 |
| Issue | 8 | Pages | 1335-43 |
| PubMed ID | 23680781 | Mgi Jnum | J:202515 |
| Mgi Id | MGI:5519204 | Doi | 10.1016/j.bbalip.2013.05.002 |
| Citation | Selkala EM, et al. (2013) Metabolic adaptation allows Amacr-deficient mice to remain symptom-free despite low levels of mature bile acids. Biochim Biophys Acta 1831(8):1335-43 |
| abstractText | 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 alpha-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. |
