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

Whereas the acc2 mutant livers were less fatty and

This preview shows page 6 out of 11 pages.

whereas the Acc2 / mutant livers were less fatty and had small oil droplets (Fig. 3 H ). Increased Hepatic AKT Activity after an HFHC Diet —Under hyperinsulinemic/euglycemic conditions, hepatic glucose pro- duction is suppressed in Acc2 / mutant mice, suggesting increased insulin sensitivity (13). Because AKT and its active form, pAKT, play an important role in insulin signaling, we decided to measure the levels of AKT and pAKT (Ser 473 ) in the livers of 3–4-month-old male, Acc2 / mutant and wild- type mice fed an HFHC diet for 2 months. The AKT level was very similar in both groups of mice, but the pAKT (Ser 473 ) level was about 40 to 50% higher in the livers of the Acc2 / mutants ( p 0.05; Fig. 4). These results suggest that insulin sensitivity was maintained in the Acc2 / mutants, partly because of improved insulin signaling through AKT activation. Significantly Fewer Hepatic Lipids Accumulate with Fasting and Refeeding —To determine the effect of continuous fatty acid oxidation on hepatic lipogenesis as a consequence of the ACC2 deletion, we followed a standard dietary protocol: a 48-h fast followed by a 48-h feeding with an FFHC diet. Under these conditions, the activities and levels of the enzymes involved in the lipogenic pathway, ACC1, ACL, and FAS, were induced in the livers of both the wild-type and the Acc2 / mutant mice (Fig. 5 A ), yielding a 2-fold increase in the ACC1 protein, a 1.8- fold increase in the ACL protein, and a 3.5-fold increase in the FAS protein in the Acc2 / mutant livers (Fig. 5 B ). Interestingly, despite the 2-fold increase in the level of ACC1 in the livers of Acc2 / mutants, the ACC activity was similar in the livers of both the Acc2 / mutant and the wild-type mice ( p 0.29; Fig. 5 C ). This similarity can be attributed to a parallel, 2-fold increase in phosphorylated ACC (pACC) that, in turn, led to reduction of these activities (Fig. 5 A ). These results also underscore the importance of the acute regulation of ACC by a phosphorylation/dephosphorylation mechanism, which results, respectively, in activation and inhibition of ACC activ- ity. FAS activity, which is not known to be regulated at the post-translational level, was about 4-fold higher in the livers of the Acc2 / mutant mice when compared with the wild-type controls (58.6 7.3 and 14.9 5.1 nmol/min/mg, respec- tively), which is consistent with the increase in FAS protein (Fig. 5, A D ). Unexpectedly, despite significant increases in the protein levels and activities of the key enzymes in the lipogenic pathway, the level of TGs in the Acc2 / mutant mouse livers was about 65% lower than that in the wild-type livers (16.03 5.75 versus 4.63 1.29 mg/g of tissue, respectively; p 0.017; Fig. 5 E). On the other hand, total cholesterol was about 20% higher in the Acc2 / mutant livers than the wild-type livers (4.11 0.23 versus 3.35 0.53 mg/g, respectively; p 0.05; Fig.
Image of page 6
You've reached the end of this preview.
  • Winter '19
  • Robert S Kiss
  • The American, Fatty acid metabolism

{[ snackBarMessage ]}

What students are saying

  • Left Quote Icon

    As a current student on this bumpy collegiate pathway, I stumbled upon Course Hero, where I can find study resources for nearly all my courses, get online help from tutors 24/7, and even share my old projects, papers, and lecture notes with other students.

    Student Picture

    Kiran Temple University Fox School of Business ‘17, Course Hero Intern

  • Left Quote Icon

    I cannot even describe how much Course Hero helped me this summer. It’s truly become something I can always rely on and help me. In the end, I was not only able to survive summer classes, but I was able to thrive thanks to Course Hero.

    Student Picture

    Dana University of Pennsylvania ‘17, Course Hero Intern

  • Left Quote Icon

    The ability to access any university’s resources through Course Hero proved invaluable in my case. I was behind on Tulane coursework and actually used UCLA’s materials to help me move forward and get everything together on time.

    Student Picture

    Jill Tulane University ‘16, Course Hero Intern