Figure 6.

Peroxisomal β-oxidation generated free acetate that used as a precursor for cholesterol biosynthesis in the STZ-induced diabetic mice.A, liver acetate was significantly higher in the diabetic mice, as further increased after treatment with C22:1 or HRO and reduced by TDYA. B, liver acetyl-CoA synthetase activity was not significantly affected in the STZ-induced diabetic mice treated with C22:1, OO, HRO, or TDYA. C, mRNA expression level of ACOT12 was upregulated in livers of the diabetic mice and strongly induced by HRO feeding. D, peroxisomal ACOT12 activity increased significantly in livers of the diabetic mice compared to the normal control, whereas peroxisomal CAT activity was very low in livers of the diabetic mice. Mean ± SEM, n = 8, ∗p < 0.05 by t test between paired conditions. E, generation of acetate and acetyl-carnitine with acetyl-CoA as a substrate by isolated peroxisome lysate. The isolated peroxisomes were lysed with addition of 0.025% (v/v) Triton-X-100, and the lysate was warmed at 37 °C for 30 min before addition of acetyl-CoA and 1 mM L-carnitine to the incubation medium. F, oxidation of C22:1 by isolated hepatocytes released acetate dose dependently, as reduced by pretreatment with TDYA. G, generation of MVA by isolated hepatocytes was stimulated in the presence of acetate or C22:1 and suppressed by pretreatment of lovastatin or TDYA. Mean ± SEM, n = 6, ∗p < 0.05 by t test between paired conditions. ACOT12, acetyl-CoA hydrolase; CAT, carnitine acyltransferase; HRO, high erucic acid rapeseed oil; MVA, mevalonic acid; OO, olive oil; STZ, streptozotocin; TDYA, 10,12-tricosadiynoic acid.