Elevated metabolic rate and skeletal muscle oxidative metabolism contribute to the reduced susceptibility of NF-B p50 null mice to obesity

被引:5
作者
Bhatt, Bankim A. [1 ]
Dedousis, Nikolaos [1 ]
Sipula, Ian J. [1 ]
O'Doherty, Robert M. [1 ,2 ]
机构
[1] Univ Pittsburgh, Div Endocrinol & Metab, Dept Med, Pittsburgh, PA USA
[2] Univ Pittsburgh, Dept Microbiol & Mol Genet, Pittsburgh, PA USA
来源
PHYSIOLOGICAL REPORTS | 2018年 / 6卷 / 18期
关键词
Inflammation; metabolic rate; NF-B p50; obesity; oxidative metabolism; skeletal muscle;
D O I
10.14814/phy2.13836
中图分类号
Q4 [生理学];
学科分类号
071003 ;
摘要
Mice with a deletion of the p50 subunit of the proinflammatory nuclear factor kappa B pathway (NF-B p50) have reduced weight compared to wild-type control mice. However, the physiological underpinning of this phenotype remains unknown. This study addressed this issue. Compared to littermate controls, lean male p50 null mice (p50(-/-)) had an increased metabolic rate (similar to 20%) that was associated with increased skeletal muscle (SkM, similar to 35%), but not liver, oxidative metabolism. These metabolic alterations were accompanied by decreases in adiposity, and tissue and plasma triglyceride levels (all similar to 30%). Notably, there was a marked decrease in skeletal muscle, but not liver, DGAT2 gene expression (similar to 70%), but a surprising reduction in muscle PPAR and CPT1 (both similar to 20%) gene expression. Exposure to a high-fat diet accentuated the diminished adiposity of p50(-/-) mice despite elevated caloric intake, whereas plasma triglycerides and free fatty acids (both similar to 30%), and liver (similar to 40%) and SkM (similar to 50%) triglyceride accumulation were again reduced compared to WT. Although SkM cytokine expression (IL-6 and TNF, each similar to 100%) were increased in p50(-/-) mice, neither cytokine acutely increased SkM oxidative metabolism. We conclude that the reduced susceptibility to diet-induced obesity and dyslipidemia in p50(-/-) mice results from an increase in metabolic rate, which is associated with elevated skeletal muscle oxidative metabolism and decreased DGAT2 expression.
引用
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页数:10
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