Elevated metabolic rate and skeletal muscle oxidative metabolism contribute to the reduced susceptibility of NF-κB p50 null mice to obesity.
Elevated metabolic rate and skeletal muscle oxidative metabolism contribute to the reduced susceptibility of NF-κB p50 null mice to obesity.
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DOI：
10.14814/phy2.13836
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发表时间：
2018-09
影响因子：
2.5
通讯作者：
O'Doherty RM
中科院分区：
文献类型：
--
作者：
Bhatt BA;Dedousis N;Sipula IJ;O'Doherty RM
与野生型对照小鼠相比，具有促炎症核因子kappaB途径p50亚单位缺失(NF-κB p50)的小鼠体重减轻。然而，这种表型的生理基础仍不清楚。这项研究解决了这个问题。与产仔对照相比，瘦雄性p50缺失小鼠(p50−/−)的代谢率增加(~20%)，这与骨骼肌(SKm，~35%)增加有关，但与肝脏的氧化代谢无关。这些代谢变化伴随着肥胖、组织和血浆甘油三酯水平的下降(均为~30%)。值得注意的是，骨骼肌中DGAT2基因的表达显著下降(~70%)，但肌肉中PPARα和CPT1基因的表达显著下降(均为~20%)。尽管热量摄入增加，但暴露在高脂肪饮食中的p50−/−小鼠的脂肪减少，而血浆甘油三酯和游离脂肪酸(均为~30%)以及肝脏(~40%)和SKM(~50%)甘油三酯的积聚与WT相比再次减少。细胞因子IL-6和肿瘤坏死因子α在p50−/−小鼠体内的表达均为100%，但这两种细胞因子均不能显著增加sKM的氧化代谢。我们得出结论，p50−/−小鼠对饮食诱导的肥胖和血脂异常的易感性降低是由于代谢率增加，这与骨骼肌氧化代谢增加和DGAT2表达减少有关。
Mice with a deletion of the p50 subunit of the proinflammatory nuclear factor kappa B pathway (NF‐κB 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 (~20%) that was associated with increased skeletal muscle (SkM, ~35%), but not liver, oxidative metabolism. These metabolic alterations were accompanied by decreases in adiposity, and tissue and plasma triglyceride levels (all ~30%). Notably, there was a marked decrease in skeletal muscle, but not liver, DGAT2 gene expression (~70%), but a surprising reduction in muscle PPAR α and CPT1 (both ~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 ~30%), and liver (~40%) and SkM (~50%) triglyceride accumulation were again reduced compared to WT. Although SkM cytokine expression (IL‐6 and TNF α, each ~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.