| First Author | Bhatt BA | Year | 2018 |
| Journal | Physiol Rep | Volume | 6 |
| Issue | 18 | Pages | e13836 |
| PubMed ID | 30251338 | Mgi Jnum | J:294394 |
| Mgi Id | MGI:6456275 | Doi | 10.14814/phy2.13836 |
| Citation | Bhatt BA, et al. (2018) Elevated metabolic rate and skeletal muscle oxidative metabolism contribute to the reduced susceptibility of NF-kappaB p50 null mice to obesity. Physiol Rep 6(18):e13836 |
| abstractText | Mice with a deletion of the p50 subunit of the proinflammatory nuclear factor kappa B pathway (NF-kappaB 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 PPARalpha 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 TNFalpha, 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. |
