Diet-induced obesity increases NF-κB signaling in reporter mice

Carlsen, Harald; Haugen, Fred; Zadelaar, Susanne; Kleemann, Robert; Kooistra, Teake; Drevon, Christian A.; Blomhoff, Rune

doi:10.1007/s12263-009-0133-6

Cited by 101 publications

(74 citation statements)

References 32 publications

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“…In our study NFκB p50 was significantly increased in heart lysates of obese female rats. This finding is in agreement with others showing that a HF diet has a proinflammatory effect, increasing NFκB activity in several tissues [55][56][57][58].…”

Section: Discussionsupporting

confidence: 93%

Influence of a High-Fat Diet on Cardiac iNOS in Female Rats

Jovanović

Sudar-Milovanović

Obradović

et al. 2017

CVP

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Overexpression of inducible nitric oxide synthase (iNOS) is a key link between high-fat (HF) diet induced obesity and cardiovascular (CV) disease. Several studies have reported that oestradiol has cardioprotective effects that may be mediated through reduction of iNOS activity/expression. In the present study, female Wistar rats were fed a standard diet or a HF diet (balanced diet for laboratory rats enriched with 42% fat) for 10 weeks. Gene and protein expression of iNOS were measured in heart tissue. HF diet-fed rats exhibited a significant increase in cardiac iNOS mRNA by 695% (p<0.05), iNOS protein level by 248% (p<0.01), without changes in nitrate/nitrite levels. Expression of CD36 protein in plasma membranes was increased by 37% (p<0.05), while the concentration of free fatty acids (FFA) was reduced by 25% (p<0.01) in HF diet-fed rats. Expression of the p50 subunit of nuclear factor-κB (NFκB-p50) in heart lysate was increased by 77% (p<0.01) in HF diet-fed rats.Expression and phosphorylation of protein kinase B (Akt) and extracellular signal-regulated kinases 1/2 (ERK1/2) in control and HF diet-fed rats were also examined. Expression of Akt and ERK1/2 were unchanged between the groups. There was a significant increase in the ratio of phospho-Akt/total Akt but not for phospho-ERK1/2/total ERK1/2/ in HF-fed rats.Estrogen receptor-α levels (by 50%; p<0.05) and serum oestradiol concentrations (by 35%; p<0.05) were examined and shown to be significantly reduced in HF diet-fed rats. Our results revealed that a HF diet led to increased iNOS expression, most likely via a mechanism involving Akt and NFκB-p50 proteins. Decreased levels of oestradiol and ERα protein in the HF-fed group, in combination with increased iNOS levels are consistent with the hypothesis that oestradiol has a cardioprotective effect through its ability to regulate iNOS expression.Key words: cardioprotection, cardiovascular disease, oestradiol, inducible nitric oxide synthase, obesity Abbreviations: Akt, protein kinase B; CD36, cluster of differentiation 36; CHD, coronary heart disease; CV, cardiovascular; CVD, cardiovascular disease; DMT2, diabetes mellitus type 2; ERα, oestrogen receptor-α; ERs, oestrogen receptors; ERK1/2, extracellular signalregulated kinases 1/2; FFA, free fatty acids; HF, high fat; HOMA-IR, HOMA-index of insulin resistance; HOMA-β, HOMA-index of β-cell function; IκB, inhibitor of NFκB; iNOS, inducible nitric oxide synthase; IR, insulin resistance; NFκB-p50, the p50 subunit of nuclear factor-κB; TES, N-[Tris(hydroxymethyl)methyl]-2-aminoethanesulfonic acid; TG, triglycerides VSMCs, vascular smooth muscle cells.

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Section: Discussionsupporting

confidence: 93%

Influence of a High-Fat Diet on Cardiac iNOS in Female Rats

Jovanović

Sudar-Milovanović

Obradović

et al. 2017

CVP

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“…Recent reports showed that HFD stimulate NF-κB in obese mice [28]. In our study we used non-obese NF-κB-Luc transgenic mice fed with HFD for 4, 8, and 12 weeks, and compared with mice fed on RD, respectively.…”

Section: Resultsmentioning

confidence: 99%

“…Studies from our laboratory have reported that IL-1β-induced NF-κB activity contributes in chemoattractant urging initial phase of prostatic inflammation that might have a capability for maintaining the chronic inflammation and proliferative inflammatory atrophy (PIA) in the prostrate, which are recognized as putative precursor lesions in the development of prostrate cancer [27]. Recently it has been shown that high-fat diet (HFD) is a stimulator for NF-κB responses in diet-induced obese mice [28]. …”

Section: Introductionmentioning

confidence: 99%

High‐fat diet increases NF‐κB signaling in the prostate of reporter mice

et al. 2010

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Background High-fat diet (HFD) is considered as a major risk factor for benign prostatic diseases and cancer in the Western world. Studies have shown an association between oxidative stress and prostatic diseases. NF-κB has been implicated in stress response and is deregulated in prostrate disorders; therefore, we sought to determine whether HFD could induce oxidative stress in the prostate which could contribute to prostatic diseases. Methods Transgenic NF-κB-Luc-Tag mice were either fed with regular diet (RD) or HFD for 12 weeks. Serial, non-invasive molecular imaging was performed to study NF-κB activation in the whole body, and in various organs including thymus, spleen, and prostate. Western blotting was used to determine the expression of NF-κB, its upstream and downstream targets in the prostate. Results Two-fold increase in whole body NF-κB activity in vivo and 2–3 fold up-regulated prostate NF-κB activity ex vivo were observed after HFD intake compared with RD controls. HFD-induced NF-κB activity was elevated remarkably in the abdominal cavity, thymus, spleen, and prostate with increase in prostrate weight. In the prostrate, an increase in the protein expression of gp91phox, p22phox, and p47phox NADPH oxidase subunits was observed suggesting the involvement of HFD in causing oxidative stress. Nuclear extracts from the prostrate tissue showed an increased expression of p65/RelA that corresponded with elevated cytosolic levels of p-IκBα, along with increased expression of downstream targets of NF-κB, nitric oxide synthase and cyclooxygenase-2. Conclusions Our findings suggest that HFD-mediated oxidative stress and deregulation of NADPH oxidase leads to NF-κB activation in the prostrate.

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“…Class II obesity and depression are set as exclusion criteria to prevent confounding, due to the association between depression and sleep disturbance [28] and because of the effect of both depression and obesity on inflammatory markers. [29, 30] Trained study staff will complete the eligibility assessments at initial contact to participants over the phone in a one-to-one interview. During this initial contact, PSQI and illness exclusions will be assessed to ensure eligibility.…”

Section: Eligibility Requirementsmentioning

confidence: 99%

Mindfulness-based intervention for prodromal sleep disturbances in older adults: Design and methodology of a randomized controlled trial

Black

O’Reilly

Olmstead

et al. 2014

Contemporary Clinical Trials

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Sleep problems are prevalent among older adults, often persist untreated, and are predictive of health detriments. Given the limitations of conventional treatments, non-pharmacological treatments such as mindfulness-based interventions (MBIs) are gaining popularity for sleep ailments. However, nothing is yet known about the impact of MBIs on sleep in older adults with prodromal sleep disturbances. This article details the design and methodology of a 6-week parallel-group RCT calibrated to test the treatment effect of the Mindful Awareness Practices (MAPs) program versus sleep hygiene education for improving sleep quality, as the main outcome, in older adults with prodromal sleep disturbances. Older adults with current sleep disturbances will be recruited from the urban Los Angeles community. Participants will be randomized into two standardized treatment conditions, MAPs and sleep hygiene education. Each condition will consist of weekly 2-hour group-based classes over the course of the 6-week intervention. The primary objective of this study is to determine if mindfulness meditation practice as engaged through the MAPs program leads to improved sleep quality relative to sleep hygiene education in older adults with prodromal sleep disturbances.

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Diet-induced obesity increases NF-κB signaling in reporter mice

Cited by 101 publications

References 32 publications

Influence of a High-Fat Diet on Cardiac iNOS in Female Rats

Influence of a High-Fat Diet on Cardiac iNOS in Female Rats

High‐fat diet increases NF‐κB signaling in the prostate of reporter mice

Mindfulness-based intervention for prodromal sleep disturbances in older adults: Design and methodology of a randomized controlled trial

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