title: Deletion of nuclear factor-κB p50 upregulates fatty acid utilization and contributes to an anti-obesity and high-endurance phenotype in mice.
abstract: The transcription factor nuclear factor-κB (NF-κB) plays an important role in regulating physiological processes such as immunity and inflammation. In addition to this primary role, NF-κB interacts physically with peroxisome proliferator-activated receptors regulating lipid metabolism-related gene expression and inhibits their transcriptional activity. Therefore, inhibition of NF-κB may promote fatty acid utilization, which could ameliorate obesity and improve endurance capacity. To test this hypothesis, we attempted to elucidate the energy metabolic status of mice lacking the p50 subunit of NF-κB (p50 KO mice) from the tissue to whole body level. p50 KO mice showed a significantly lower respiratory quotient throughout the day than did wild-type (WT) mice; this decrease was associated with increased fatty acid oxidation activity in liver and gastrocnemius muscle of p50 KO mice. p50 KO mice that were fed a high-fat diet were also resistant to fat accumulation and adipose tissue inflammation. Furthermore, p50 KO mice showed a significantly longer maximum running time compared with WT mice, with a lower respiratory exchange ratio during exercise as well as higher residual muscle glycogen content and lower blood lactate levels after exercise. These results suggest that p50 deletion facilitates fatty acid catabolism, leading to an anti-obesity and high-endurance phenotype of mice and supporting the idea that NF-κB is an important regulator of energy metabolism.
authors.affiliation: Biological Science Laboratories, Kao Corporation, Tochigi, Japan.
authors.forename: Yoshihiko
authors.initials: Y
authors.lastname: Minegishi
authors.affiliation: Biological Science Laboratories, Kao Corporation, Tochigi, Japan.
authors.forename: Satoshi
authors.initials: S
authors.lastname: Haramizu
authors.affiliation: Biological Science Laboratories, Kao Corporation, Tochigi, Japan.
authors.forename: Koichi
authors.initials: K
authors.lastname: Misawa
authors.affiliation: Biological Science Laboratories, Kao Corporation, Tochigi, Japan.
authors.forename: Akira
authors.initials: A
authors.lastname: Shimotoyodome
authors.affiliation: Biological Science Laboratories, Kao Corporation, Tochigi, Japan.
authors.forename: Tadashi
authors.initials: T
authors.lastname: Hase
authors.affiliation: Biological Science Laboratories, Kao Corporation, Tochigi, Japan murase.takatoshi@kao.co.jp.
authors.forename: Takatoshi
authors.initials: T
authors.lastname: Murase
mesh_terms: D000273:Adipose Tissue / Q000378:metabolism; D000818:Animals; D059305:Diet, High-Fat; D005227:Fatty Acids / Q000378:metabolism*; D007249:Inflammation; D050356:Lipid Metabolism / Q000235:genetics*; D008099:Liver / Q000378:metabolism*; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D018482:Muscle, Skeletal / Q000378:metabolism*; D052002:NF-kappa B p50 Subunit / Q000235:genetics* / Q000378:metabolism; D009765:Obesity / Q000235:genetics*; D010084:Oxidation-Reduction; D047492:Peroxisome Proliferator-Activated Receptors / Q000378:metabolism; D010641:Phenotype; D010807:Physical Endurance / Q000235:genetics*; D015854:Up-Regulation
chemical_list: D005227:Fatty Acids; D052002:NF-kappa B p50 Subunit; D047492:Peroxisome Proliferator-Activated Receptors; C073701:Nfkb1 protein, mouse
keywords: energy metabolism; fatty acid oxidation; nuclear factor-κB