Acetyl-CoA carboxylase 2-:- mutant mice are protected against fatty liver under high-fat, high-carb

Acetyl coa carboxylase 2 affects hepatic lipid

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Acetyl-CoA Carboxylase 2 Affects Hepatic Lipid Metabolism APRIL 6, 2012• VOLUME 287•NUMBER 15 JOURNAL OF BIOLOGICAL CHEMISTRY 12581
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tion and an HFHC diet and other dietary conditions, we fed 3–4-month-old Acc2 / mutant mice an HFHC diet for 2 months. We found a significant decrease in the protein levels of the key enzymes in the lipogenic pathways as follows: 65% for ACC1, 30% for ACL, and 40% for FAS (Fig. 3, B and C ). In liver extracts, ACC activity was about 30% lower ( p 0.019; Fig. 3 D ) and FAS activity was about 60% lower ( p 0.01; Fig. 3 E ) in Acc2 / mutant mice. When the effects of the HFHC diet were compared with those of the normal diet (Fig. 2), hepatic TGs were elevated in both the wild-type and Acc2 / mutants, with the level of TGs being statistically significantly lower in the Acc2 / tissues ( p 0.001; Fig. 3 F ). Interestingly, although the FIGURE 2. Representative Western blots of lipogenic enzymes, and TG and cholesterol levels in liver extracts from control and Acc2 / mutant mice fed a normal diet. In Western blot analyses, crude liver extracts (“Experimental Procedures”) were separated by 4–12% NuPAGE MES gels. A , 30- g protein samples of liver extracts from control and Acc2 / mutant mice were separated by gel electrophoresis. Antibodies against ACL, ACC1, and FAS were used to detect their respective levels with ECL. The bottom panel shows a representative Western blot after staining with Ponceau S to indicate equal loading. B , the respective bands in the blots in A were scanned and quantified. C and D, activities of ACC and FAS in liver crude extracts, respectively. E and F, triglyceride and cholesterol levels in liver extracts from the two groups of mice were determined as described under “Experimental Procedures.” FIGURE 3. Body weights, representative Western blots, enzyme activities of ACC and FAS, and levels of TGs and cholesterol in samples of liver extracts from control and Acc2 / mutant mice fed a high-fat, high-carbohydrate diet. A , body weights of 5-week-old male mice fed a high-fat, high-carbohydrate diet for 16 weeks ( n 20). B–H , represent data from 3–4-month-old male mice fed a high-fat, high-carbohydrate diet for 2 months. B and C, representative Western blots of liver extracts and the quantification of the respective bands as described for Fig. 2. For detection of ACC, we used ACC1 antibodies, as we described previously (3). D and E, enzyme activities of ACC and FAS, respectively. F and G, levels of TGs and cholesterol in liver extracts, as determined by enzymatic methods. H , Oil Red O staining of frozen liver tissues showing the accumulation of oil droplets in orange ; the bar indicates 20 m. Acetyl-CoA Carboxylase 2 Affects Hepatic Lipid Metabolism 12582 JOURNAL OF BIOLOGICAL CHEMISTRY VOLUME 287•NUMBER 15• APRIL 6, 2012
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level of hepatic cholesterol was higher in the liver extracts of the Acc2 / mutants, this difference did not reach statistical sig- nificance ( p 0.09; Fig. 3 G ). Consistent with these low levels of hepatic TGs, staining of the liver tissues with Oil Red O showed that the wild-type livers were very fatty with large oil droplets,
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  • Winter '19
  • Robert S Kiss
  • The American, Fatty acid metabolism

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