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

Trols p 005 table 1 in addition serum glucose levels

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trols ( p 0.05; Table 1). In addition, serum glucose levels in the Acc2 / mutant mice were 10% lower than those in the wild- Acetyl-CoA Carboxylase 2 Affects Hepatic Lipid Metabolism APRIL 6, 2012• VOLUME 287•NUMBER 15 JOURNAL OF BIOLOGICAL CHEMISTRY 12579
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type mice ( p 0.1; Table 1). When both groups of mice were fed an HFHC diet, the Acc2 / mutants had significantly lower serum glucose levels ( p 0.01; Table 1). In addition, the serum levels of TGs and VLDL cholesterol were about 40% lower in the Acc2 / mutants (Table 1). Interestingly, however, the serum levels of total, HDL, and LDL cholesterols were about 30% higher in the Acc2 / mutant mice ( p 0.05; Table 1). When both groups of mice fasted for 48 h, the serum levels of total cholesterol were 17% lower ( p 0.05; Table 1) and those of TGs were 50% lower (Table 1) in the Acc2 / mutants. No significant differences were found in serum glucose and LDL cholesterol levels between both types of mice (Table 1). To determine serum levels of the various metabolites under lipogenic conditions, both groups of mice underwent a 48-h fast and a 48-h feeding with an FFHC diet. This dietary regimen resulted in 30% lower serum levels of TGs and VLDL choles- terol ( p 0.05; Table 1) and 30, 25, and 75% higher serum levels of total, HDL, and LDL cholesterols, respectively, in the Acc2 / mutants ( p 0.05; Table 1). The serum levels of glu- cose were similar in both groups of mice. The presence of NEFAs in blood serum is an indicator of lipolytic activities and fat mobilization in adipose tissue and in fat-oxidizing tissues such as muscle. In addition, a high serum level of NEFAs has been linked to insulin resistance and indi- cates a slower fatty acid oxidation rate. When we measured the serum levels of these fatty acids in both groups of mice under different dietary conditions, we found that the levels of the NEFAs were lower in the Acc2 / mutants no matter the die- tary condition (Table 1): normal diet ( p 0.02), fasting and refeeding ( p 0.3), starvation ( p 0.006), and an HFHC diet ( p 0.04; Table 1). These results suggest that although white adipose tissues have higher lipolytic activity (16), NEFAs are lower in the blood, most likely because of increased delivery of free fatty acids to different tissues. Reduced Body Weight and Smaller Epididymal Fat Pads and Livers in Acc2 / Mutant Mice under Different Dietary Conditions —We have previously shown that Acc2 / mutant mice are protected against obesity and diabetes even when fed HF or HFHC diets (12, 13). In this study, we determined the effects of different dietary conditions, including those charac- teristic of a Western HFHC diet, on the morphology of Acc2 / mutant and wild-type mice. When fed a normal diet, the Acc2 / mutant mice weighed about 25% less ( p 0.0005; Fig. 1 A ); and the livers and epididymal fat pads of the Acc2 / mutant mice weighed about 20% less than those of the wild- type controls and were significantly lower when calculated per body weight ( p 0.001; Fig. 1, B and C ). We also measured morphological changes after 48 h of starvation and after refeed- ing with an FFHC diet for another 48 h. Before fasting, the body weight of the Acc2 /
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  • Winter '19
  • Robert S Kiss
  • The American, Fatty acid metabolism

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