What would be the effect on fatty acid oxidation in an Acc2-/-/Cpt1-/- double knockout mouse?

• A. Increased triglyceride synthesis
• B. Increased insulin secretion
• C. Decreased fatty acid oxidation
• D. Increased malonyl-CoA production

Answer: (C)

The correct answer indicates a decrease in fatty acid oxidation in an Acc2-/-/Cpt1-/- double knockout mouse.

To understand this, it's important to consider the roles of two enzymes affected by the knockouts: Acetyl-CoA carboxylase (ACC2) and Carnitine palmitoyltransferase 1 (CPT1). ACC2 is crucial for regulating fatty acid metabolism, as it converts Acetyl-CoA to malonyl-CoA. Malonyl-CoA is a key intermediate in fatty acid synthesis and, importantly, it inhibits CPT1.

CPT1 is responsible for transporting long-chain fatty acids into the mitochondria for beta-oxidation, where they are broken down for energy production. In a scenario with the double knockout of both ACC2 and CPT1, the inhibition of fatty acid oxidation occurs due to the lack of CPT1 functioning. Consequently, fatty acids are unable to enter the mitochondria effectively, directly leading to decreased fatty acid oxidation despite the potential accumulation of fatty acids in the cytosol.

Thus, the knockout of ACC2 eliminates the production of malonyl-CoA that inhibits CPT1, but the absence of CPT1 prevents the transportation and subsequent