Shc proteins influence the activities of enzymes involved in fatty acid oxidation and ketogenesis

Kevork Hagopian, Alexey Tomilov, Natalia Tomilova, Kyoungmi Kim, Sandra L. Taylor, Adam K. Lam, Gino A Cortopassi, Roger B. McDonald, Jon J Ramsey

Research output: Contribution to journalArticle

8 Citations (Scopus)

Abstract

Objectives: ShcKO mice have low body fat and resist weight gain on a high fat diet, indicating that Shc proteins may influence enzymes involved in β-oxidation. To investigate this idea, the activities of β-oxidation and ketone body metabolism enzymes were measured. Methods: The activities of β-oxidation enzymes (acyl-CoA dehydrogenase, 3-hydroxyacyl-CoA dehydrogenase and ketoacyl-CoA thiolase) in liver and hindlimb skeletal muscle, ketolytic enzymes (acetoacetyl-CoA thiolase, β-hydroxybutyrate dehydrogenase and 3-oxoacid-CoA transferase) in skeletal muscle, and ketogenic enzymes (acetoacetyl-CoA thiolase and β-hydroxybutyrate dehydrogenase) in liver were measured from wild-type and ShcKO mice. Results: The activities of β-oxidation enzymes were increased (P <.05) in the ShcKO compared to wild-type mice in the fasted but not the fed state. In contrast, no uniform increases in the ketolytic enzyme activities were observed between ShcKO and wild-type mice. In liver, the activities of ketogenic enzymes were increased (P <.05) in ShcKO compared to wild-type mice in both the fed and fasted states. Levels of phosphorylated hormone sensitive lipase from adipocytes were also increased (P <.05) in fasted ShcKO mice. Conclusion: These studies indicate that the low Shc levels in ShcKO mice result in increased liver and muscle β-oxidation enzyme activities in response to fasting and induce chronic increases in the activity of liver ketogenic enzymes. Decreases in the level of Shc proteins should be considered as possible contributors to the increase in activity of fatty acid oxidation enzymes in response to physiological conditions which increase reliance on fatty acids as a source of energy.

Original languageEnglish (US)
Pages (from-to)1703-1713
Number of pages11
JournalMetabolism: Clinical and Experimental
Volume61
Issue number12
DOIs
StatePublished - Dec 2012

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Fatty Acids
Enzymes
Proteins
Acetyl-CoA C-Acetyltransferase
Hydroxybutyrate Dehydrogenase
Liver
Skeletal Muscle
3-Hydroxyacyl-CoA Dehydrogenase
Coenzyme A-Transferases
Acyl-CoA Dehydrogenase
Sterol Esterase
Keto Acids
Ketone Bodies
High Fat Diet
Coenzyme A
Hindlimb
Adipocytes
Weight Gain
Adipose Tissue
Fasting

Keywords

  • Fasting
  • Fatty acid oxidation
  • Fed to starved transition
  • Liver
  • Skeletan muscle

ASJC Scopus subject areas

  • Endocrinology
  • Endocrinology, Diabetes and Metabolism

Cite this

Shc proteins influence the activities of enzymes involved in fatty acid oxidation and ketogenesis. / Hagopian, Kevork; Tomilov, Alexey; Tomilova, Natalia; Kim, Kyoungmi; Taylor, Sandra L.; Lam, Adam K.; Cortopassi, Gino A; McDonald, Roger B.; Ramsey, Jon J.

In: Metabolism: Clinical and Experimental, Vol. 61, No. 12, 12.2012, p. 1703-1713.

Research output: Contribution to journalArticle

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abstract = "Objectives: ShcKO mice have low body fat and resist weight gain on a high fat diet, indicating that Shc proteins may influence enzymes involved in β-oxidation. To investigate this idea, the activities of β-oxidation and ketone body metabolism enzymes were measured. Methods: The activities of β-oxidation enzymes (acyl-CoA dehydrogenase, 3-hydroxyacyl-CoA dehydrogenase and ketoacyl-CoA thiolase) in liver and hindlimb skeletal muscle, ketolytic enzymes (acetoacetyl-CoA thiolase, β-hydroxybutyrate dehydrogenase and 3-oxoacid-CoA transferase) in skeletal muscle, and ketogenic enzymes (acetoacetyl-CoA thiolase and β-hydroxybutyrate dehydrogenase) in liver were measured from wild-type and ShcKO mice. Results: The activities of β-oxidation enzymes were increased (P <.05) in the ShcKO compared to wild-type mice in the fasted but not the fed state. In contrast, no uniform increases in the ketolytic enzyme activities were observed between ShcKO and wild-type mice. In liver, the activities of ketogenic enzymes were increased (P <.05) in ShcKO compared to wild-type mice in both the fed and fasted states. Levels of phosphorylated hormone sensitive lipase from adipocytes were also increased (P <.05) in fasted ShcKO mice. Conclusion: These studies indicate that the low Shc levels in ShcKO mice result in increased liver and muscle β-oxidation enzyme activities in response to fasting and induce chronic increases in the activity of liver ketogenic enzymes. Decreases in the level of Shc proteins should be considered as possible contributors to the increase in activity of fatty acid oxidation enzymes in response to physiological conditions which increase reliance on fatty acids as a source of energy.",
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author = "Kevork Hagopian and Alexey Tomilov and Natalia Tomilova and Kyoungmi Kim and Taylor, {Sandra L.} and Lam, {Adam K.} and Cortopassi, {Gino A} and McDonald, {Roger B.} and Ramsey, {Jon J}",
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T1 - Shc proteins influence the activities of enzymes involved in fatty acid oxidation and ketogenesis

AU - Hagopian, Kevork

AU - Tomilov, Alexey

AU - Tomilova, Natalia

AU - Kim, Kyoungmi

AU - Taylor, Sandra L.

AU - Lam, Adam K.

AU - Cortopassi, Gino A

AU - McDonald, Roger B.

AU - Ramsey, Jon J

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N2 - Objectives: ShcKO mice have low body fat and resist weight gain on a high fat diet, indicating that Shc proteins may influence enzymes involved in β-oxidation. To investigate this idea, the activities of β-oxidation and ketone body metabolism enzymes were measured. Methods: The activities of β-oxidation enzymes (acyl-CoA dehydrogenase, 3-hydroxyacyl-CoA dehydrogenase and ketoacyl-CoA thiolase) in liver and hindlimb skeletal muscle, ketolytic enzymes (acetoacetyl-CoA thiolase, β-hydroxybutyrate dehydrogenase and 3-oxoacid-CoA transferase) in skeletal muscle, and ketogenic enzymes (acetoacetyl-CoA thiolase and β-hydroxybutyrate dehydrogenase) in liver were measured from wild-type and ShcKO mice. Results: The activities of β-oxidation enzymes were increased (P <.05) in the ShcKO compared to wild-type mice in the fasted but not the fed state. In contrast, no uniform increases in the ketolytic enzyme activities were observed between ShcKO and wild-type mice. In liver, the activities of ketogenic enzymes were increased (P <.05) in ShcKO compared to wild-type mice in both the fed and fasted states. Levels of phosphorylated hormone sensitive lipase from adipocytes were also increased (P <.05) in fasted ShcKO mice. Conclusion: These studies indicate that the low Shc levels in ShcKO mice result in increased liver and muscle β-oxidation enzyme activities in response to fasting and induce chronic increases in the activity of liver ketogenic enzymes. Decreases in the level of Shc proteins should be considered as possible contributors to the increase in activity of fatty acid oxidation enzymes in response to physiological conditions which increase reliance on fatty acids as a source of energy.

AB - Objectives: ShcKO mice have low body fat and resist weight gain on a high fat diet, indicating that Shc proteins may influence enzymes involved in β-oxidation. To investigate this idea, the activities of β-oxidation and ketone body metabolism enzymes were measured. Methods: The activities of β-oxidation enzymes (acyl-CoA dehydrogenase, 3-hydroxyacyl-CoA dehydrogenase and ketoacyl-CoA thiolase) in liver and hindlimb skeletal muscle, ketolytic enzymes (acetoacetyl-CoA thiolase, β-hydroxybutyrate dehydrogenase and 3-oxoacid-CoA transferase) in skeletal muscle, and ketogenic enzymes (acetoacetyl-CoA thiolase and β-hydroxybutyrate dehydrogenase) in liver were measured from wild-type and ShcKO mice. Results: The activities of β-oxidation enzymes were increased (P <.05) in the ShcKO compared to wild-type mice in the fasted but not the fed state. In contrast, no uniform increases in the ketolytic enzyme activities were observed between ShcKO and wild-type mice. In liver, the activities of ketogenic enzymes were increased (P <.05) in ShcKO compared to wild-type mice in both the fed and fasted states. Levels of phosphorylated hormone sensitive lipase from adipocytes were also increased (P <.05) in fasted ShcKO mice. Conclusion: These studies indicate that the low Shc levels in ShcKO mice result in increased liver and muscle β-oxidation enzyme activities in response to fasting and induce chronic increases in the activity of liver ketogenic enzymes. Decreases in the level of Shc proteins should be considered as possible contributors to the increase in activity of fatty acid oxidation enzymes in response to physiological conditions which increase reliance on fatty acids as a source of energy.

KW - Fasting

KW - Fatty acid oxidation

KW - Fed to starved transition

KW - Liver

KW - Skeletan muscle

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