Abstract
To study the metabolic activity of NF-kappaB, we investigated phenotypes of two different mouse models with elevated NF-kappaB activities. The transcriptional activity of NF-kappaB is enhanced either by overexpression of NF-kappaB p65 (RelA) in aP2-p65 mice or inactivation of NF-kappaB p50 (NF-kappaB1) through gene knock-out. In these models, energy expenditure was elevated in day and night time without a change in locomotion. The mice were resistant to adulthood obesity and diet-induced obesity without reduction in food intake. The adipose tissue growth and adipogenesis were inhibited by the elevated NF-kappaB activity. Peroxisome proliferator-activator receptor gamma expression was reduced by NF-kappaB at the transcriptional level. The two models exhibited elevated inflammatory cytokines (tumor necrosis factor-alpha and interleukin-6) in adipose tissue and serum. However, insulin sensitivity was not reduced by the inflammation in the mice on a chow diet. On a high fat diet, the mice were protected from insulin resistance. The glucose infusion rate was increased more than 30% in the hyperinsulinemic-euglycemic clamp test. Our data suggest that the transcription factor NF-kappaB promotes energy expenditure and inhibits adipose tissue growth. The two effects lead to prevention of adulthood obesity and dietary obesity. The energy expenditure may lead to disassociation of inflammation with insulin resistance. The study indicates that inflammation may prevent insulin resistance by eliminating lipid accumulation.
Highlights
The IKK2/NF-B signaling pathway plays an important role in the control of inflammation, apoptosis, carcinogenesis, and oxidative stress [1]
We investigated the metabolic activity of NF-B using the NF-B transgenic mice in the current study
The common form of NF-B contains two subunits: p65 (RelA) and p50 (NF-B1). p65 contains the transactivation domain and mediates transcriptional activation of target genes. p50 usually inhibits the transcriptional activity of p65 [12], and the inhibition disappears in the p50-KO mice [13]
Summary
Animals—The male p50-KO mice and their controls were purchased from the Jackson Laboratory (Bar Harbor, ME). The metabolic phenotype was examined in the aP2-p65 Tg mice by monitoring the body weight, body composition, food intake, and energy expenditure. The DNA-protein reaction and gel shift assay were 9% lower in body weight (Fig. 2A) and had 68% less fat content conducted as described elsewhere [29]. To understand the mechanism of reduction in overnight-fasted mice with [3-3H]glucose and 2-deoxy-D-[1- body fat, we examined food intake and energy expenditure in. The energy expenditure was not due to an increase all real time RT-PCR results were performed using the two- in physical activity because the locomotor activity was not tailed, unpaired, Student’s t test for the WT littermates versus changed in the Tg mice (Fig. 2G).
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