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Polyunsaturated fatty acids do not activate AMP-activated protein kinase in mouse tissues
Agnieszka Dobrzyn1, Pawel Dobrzyn, Makoto Miyazaki
1Department of Biochemistry, University of Wisconsin-Madison, Madison, WI 53706, USA.
Abstract:
Stearoyl-CoA desaturase 1 (SCD1) deficiency partitions fatty acids away from lipid synthesis towards fatty acid oxidation in liver and skeletal muscle in part due to activation of AMP-activated protein kinase (AMPK) pathway. The mechanism of AMPK activation by SCD1 mutation is unknown, however since SCD1-/- animals have increased relative amounts of polyunsaturated fatty acids (PUFA), we hypothesized that the increased levels of PUFA might be responsible for the activation of AMPK in SCD1 deficient mice. Therefore, the present study was undertaken to analyze the effect of PUFA on AMPK in liver, skeletal muscle, and heart. We fed mice ad libitum for 14 days with diet supplemented with fish oil (5% fat). As expected, fish oil supplementation significantly increased n-3 PUFA content in each of the analyzed tissues. Hepatic mRNA levels of fatty acid synthase and acyl-CoA oxidase decreased by 92% and increased by 60%, respectively, consistent with known PUFA effects. However, after 14 days of PUFA feeding, we did not find any changes in AMPK phosphorylation and protein content in mouse liver, skeletal muscle, and heart. The data suggest that PUFA are not involved in AMPK activation in mouse tissues and that the increased activity of AMPK in SCD1-/- mice is probably PUFA-independent.
Insights
Polyunsaturated fatty acids (PUFA) do not activate AMP-activated protein kinase (AMPK) in mice. This suggests that increased AMPK activity in Stearoyl-CoA desaturase 1 (SCD1) deficient mice is independent of PUFA levels.
Area of Science:
- Biochemistry
- Metabolic pathways
- Molecular biology
Background:
- Stearoyl-CoA desaturase 1 (SCD1) deficiency alters fatty acid metabolism, promoting oxidation over synthesis.
- AMP-activated protein kinase (AMPK) pathway activation is implicated in SCD1 deficiency.
- SCD1-deficient mice exhibit elevated polyunsaturated fatty acids (PUFA), prompting investigation into their role in AMPK activation.
Purpose of the Study:
- To investigate the direct effect of polyunsaturated fatty acids (PUFA) on AMP-activated protein kinase (AMPK) activation.
- To determine if increased PUFA levels in SCD1 deficiency are responsible for AMPK activation in liver, skeletal muscle, and heart.
Main Methods:
- Mice were fed a diet supplemented with fish oil (rich in n-3 PUFA) for 14 days.
- Tissue samples (liver, skeletal muscle, heart) were analyzed for PUFA content.
- AMPK phosphorylation and protein levels were assessed in the analyzed tissues.
Main Results:
- Fish oil supplementation significantly increased n-3 PUFA content in all examined tissues.
- Hepatic mRNA levels of fatty acid synthase and acyl-CoA oxidase changed consistent with known PUFA effects.
- No significant changes in AMPK phosphorylation or protein content were observed in liver, skeletal muscle, or heart after PUFA feeding.
Conclusions:
- Polyunsaturated fatty acids (PUFA) do not appear to be involved in the activation of AMP-activated protein kinase (AMPK) in mouse tissues.
- The observed AMPK activation in Stearoyl-CoA desaturase 1 (SCD1) deficient mice is likely independent of elevated PUFA levels.
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