Hormonal
Knocking out ACC2 improves insulin sensitivity in high-fat-fed mice by reducing intracellular diacylglycerol and novel PKC activity, thereby preventing fat-induced insulin resistance.
This mechanism suggests that reducing intracellular fat metabolites (like diacylglycerol) can improve insulin sensitivity even in the presence of high fat intake. This supports the idea that metabolic health is more about where fat is stored and oxidized than just total fat intake.
Acc2-/- mice were protected from fat-induced peripheral and hepatic insulin resistance. These improvements in insulin-stimulated glucose metabolism were associated with reduced diacylglycerol content in muscle and liver, decreased PKCtheta activity in muscle and PKCzeta activity in liver, and increased insulin-stimulated Akt2 activity in these tissues.
Why this rating
High-quality mechanistic data using hyperinsulinemic-euglycemic clamps and tissue-specific biochemical assays.
Source
Continuous fat oxidation in acetyl–CoA carboxylase 2 knockout mice increases total energy expenditure, reduces fat mass, and improves insulin sensitivity
Cheol Soo Choi et al. · Proceedings of the National Academy of Sciences · 2007
DOI 10.1073/pnas.0706794104
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