Continuous fat oxidation in acetyl-CoA carboxylase 2 knockout mice increases total energy expenditure, reduces fat mass, and improves insulin sensitivity.

Continuous fat oxidation in acetyl-CoA carboxylase 2 knockout mice increases total energy expenditure, reduces fat mass, and improves insulin sensitivity. Research Abstract Details 

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Continuous fat oxidation in acetyl-CoA carboxylase 2 knockout mice increases total energy expenditure, reduces fat mass, and improves insulin sensitivity. Abstract Text:

Cheol Soo Choi,David B Savage,Lutfi Abu-Elheiga,Zhen-Xiang Liu,Sheene Kim,Ameya Kulkarni,Alberto Distefano,Yu-Jin Hwang,Richard M Reznick,Roberto Codella,Dongyan Zhang,Gary W Cline,Salih J Wakil,Gerald I Shulman,Cheol Soo Choi,David B Savage,Lutfi Abu-Elheiga,Zhen-Xiang Liu,Sheene Kim,Ameya Kulkarni,Alberto Distefano,Yu-Jin Hwang,Richard M Reznick,Roberto Codella,Dongyan Zhang,Gary W Cline,Salih J Wakil,Gerald I Shulman,

Acetyl-CoA carboxylase 2 (ACC)2 is a key regulator of mitochondrial fat oxidation. To examine the impact of ACC2 deletion on whole-body energy metabolism, we measured changes in substrate oxidation and total energy expenditure in Acc2(-/-) and WT control mice fed either regular or high-fat diets. To determine insulin action in vivo, we also measured whole-body insulin-stimulated liver and muscle glucose metabolism during a hyperinsulinemic-euglycemic clamp in Acc2(-/-) and WT control mice fed a high-fat diet. Contrary to previous studies that have suggested that increased fat oxidation might result in lower glucose oxidation, both fat and carbohydrate oxidation were simultaneously increased in Acc2(-/-) mice. This increase in both fat and carbohydrate oxidation resulted in an increase in total energy expenditure, reductions in fat and lean body mass and prevention from diet-induced obesity. Furthermore, 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 PKC activity in muscle and PKCepsilon activity in liver, and increased insulin-stimulated Akt2 activity in these tissues. Taken together with previous work demonstrating that Acc2(-/-) mice have a normal lifespan, these data suggest that Acc2 inhibition is a viable therapeutic option for the treatment of obesity and type 2 diabetes.

Continuous fat oxidation in acetyl-CoA carboxylase 2 knockout mice increases total energy expenditure, reduces fat mass, and improves insulin sensitivity. Publishing Authors By Initials

CS Choi,DB Savage,L Abu-Elheiga,ZX Liu,S Kim,A Kulkarni,A Distefano,YJ Hwang,RM Reznick,R Codella,D Zhang,GW Cline,SJ Wakil,GI Shulman,CS Choi,DB Savage,L Abu-Elheiga,ZX Liu,S Kim,A Kulkarni,A Distefano,YJ Hwang,RM Reznick,R Codella,D Zhang,GW Cline,SJ Wakil,GI Shulman,

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Continuous fat oxidation in acetyl-CoA carboxylase 2 knockout mice increases total energy expenditure, reduces fat mass, and improves insulin sensitivity. Journal Published:

PUBLICATION TYPE: Research Support, Non-U.S. Gov

Journal: Proceedings of the National Academy of Sciences of

VOLUME: 104

Page Numbers: 16480-5

Journal Abbreviation: Proc. Natl. Acad. Sci. U.S.A.

ISSN: 0027-8424

DAY: 8

MONTH: 10

YEAR: 2007

Continuous fat oxidation in acetyl-CoA carboxylase 2 knockout mice increases total energy expenditure, reduces fat mass, and improves insulin sensitivity. Information

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LANGUAGE: eng

NlmUniqueID: 7505876

Continuous fat oxidation in acetyl-CoA carboxylase 2 knockout mice increases total energy expenditure, reduces fat mass, and improves insulin sensitivity. Keywords Mesh Terms:

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Grant and Affiliation Information for Continuous fat oxidation in acetyl-CoA carboxylase 2 knockout mice increases total energy expenditure, reduces fat mass, and improves insulin sensitivity.

AFFILIATION: Department of Internal Medicine, Yale University School of Medicine, New Haven, CT 06510, USA.

Country: United States

AGENCY: United Kingdom Wellcome T

GRANT: U24 DK-76169

ACRONYM: DK

MEDLINETA: Proc Natl Acad Sci U S A

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