NOTE:  NF-kB is a cellular transcription factor that has been reported to both inhibit and to activate apoptosis (controled cell killing).  In cancer cells it is known for inhibition of apoptosis.  Cell signals that activate it cause proliferation and cancer growth. It is held inactive by the inhibitor of kappa beta (IkB), while IkB kinase (IKKb) phosporylates the inhibitor, releasing and activating NF-kB. 

Biochem Biophys Res Commun. 1996 Dec 13;229(2):643-7.

Nuclear factor kB is activated by arachidonic acid but not by eicosapentaenoic acid.

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The omega-6 arachidonic acid supplementation of the human promonocytic cell line U937 strongly stimulates the nuclear translocation of the transcription factor NF-kB. Inhibitors of arachidonate oxidative metabolism prevent NF-kB activation, indirectly indicating a role for prostaglandin and leukotriene metabolites in the genesis of this phenomenon. Of note, omega-3 eicosapentaenoic acid does not exert any effect on NF-kB DNA binding. In subsequent experiments, prostaglandin E2 consistently showed the ability to activate NF-kB in U937 promonocytic cells, as well as in J774 macrophages. NF-kB activation by arachidonate, together with the lack of effect by eicosapentaenoic acid, suggests a way to modulate the expression of certain genes by means of a suitable dietary n-6/n-3 fatty acid ratio.


Cell. 2001 Jan 12;104(1):33-42.

Bcl10 is a positive regulator of antigen receptor-induced activation of NF-kappaB and neural tube closure.

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BcL10, a  caspase recruitment domain (CARD)-containing protein identified from the t(1;14)(p22;q32) breakpoint in mucosa-associated lymphoid tissue (MALT) lymphomas, has been shown to induce apoptosis and activate NF-kappaB in vitro. We show that one-third of bcl10-/- embryos developed exencephaly, leading to embryonic lethality. Surprisingly, bcl10-/- cells retained susceptibility to various apoptotic stimuli in vivo and in vitro. However, surviving bcl10-/- mice were severely immunodeficient and bcl10-/- lymphocytes are defective in antigen receptor or PMA/Ionomycin-induced activation. Early tyrosine phosphorylation, MAPK and AP-1 activation, and Ca2+ signaling were normal in mutant lymphocytes, but antigen receptor-induced NF-kappaB activation was absent. Thus, Bcl10 functions as a positive regulator of lymphocyte proliferation that specifically connects antigen receptor signaling in B and T cells to NF-kappaB activation.

And of course cell proliferation promotes growth of carcinoma cells.



PMCID: PMC3375919

Bcl10 Links Saturated Fat Overnutrition with Hepatocellular NF-κB Activation and Insulin Resistance


 Excess serum free fatty acids (FFAs) are fundamental to the pathogenesis of insulin resistance. With high fat feeding, FFAs activate NF-κB in target tissues, initiating negative cross-talk with insulin signaling. However, the mechanisms underlying FFA-dependent NF-κB activation remain unclear. Here we demonstrate that the saturated FA, palmitate, requires Bcl10 for NF-κB activation in hepatocytes. Uptake of palmitate, metabolism to diacylglycerol, and subsequent activation of PKC appear to mechanistically link palmitate with Bcl10, known as a central component of a signaling complex that, along with CARMA3 and MALT1, activates NF-κB downstream of selected cell surface receptors. Consequently, Bcl10-deficient mice are protected from hepatic NF-κB activation and insulin resistance following brief high fat diet, suggesting that Bcl10 plays a major role in the metabolic consequences of acute overnutrition. Surprisingly, while CARMA3 also participates in the palmitate response, MALT1 is completely dispensable, thereby revealing an apparent non-classical role for Bcl10 in NF-κB signaling.


Genes Nutr. 2009 Sep; 4(3): 215–222.
Published online 2009 Aug 26. doi: 10.1007/s12263-009-0133-6
PMCID: PMC2745749

Diet-induced obesity increases NF-kB signaling in reporter mice
Harald Carlsen,corresponding author1 Fred Haugen,1 Susanne Zadelaar,2 Robert Kleemann,2 Teake Kooistra,2 Christian A. Drevon,1 and Rune Blomhoff1


The nuclear factor (NF)-kB is a primary regulator of inflammatory responses and may be linked to pathology associated with obesity. We investigated the progression of NF-kB activity during a 12-week feeding period on a high-fat diet (HFD) or a low-fat diet (LFD) using NF-?B luciferase reporter mice. In vivo imaging of luciferase activity showed that NF-kB activity was higher in the HFD mice compared with LFD-fed mice. Thorax region of HFD females displayed fourfold higher activity compared with LFD females, while no such increase was evident in males. In male HFD mice, abdominal NF-kB activity was increased twofold compared with the LFD males, while females had unchanged NF-kB activity in the abdomen by HFD. HFD males, but not females, exhibited evident glucose intolerance during the study.

In conclusion, HFD increased NF-kB activity in both female and male mice. However, HFD differentially increased activity in males and females. The moderate increase in abdomen of male mice may be linked to glucose intolerance.

Diabetes 2015;64:2015–2027 | DOI: 10.2337/db14-0093

Central Inhibition of IKKb/NF-kB Signaling Attenuates High-Fat Diet–Induced Obesity and Glucose Intolerance

Jonas Benzler,1 Goutham K. Ganjam,2 Dominik Pretz,1 Rebecca Oelkrug,1 Christiane E. Koch,1 Karen Legler,1 Sigrid Stöhr,1 Carsten Culmsee,2 Lynda M. Williams,3 and Alexander Tups1,4

Metabolic inflammation in the central nervous system might be causative for the development of over nutrition induced metabolic syndrome and related disorders, such as obesity, leptin and insulin resistance, and type 2 diabetes. Here we investigated whether nutritive and genetic inhibition of the central IkB kinase b (IKKb)/nuclear factor-kB (NF-kB) pathway in diet-induced obese (DIO) and leptin-deficient mice improves these metabolic impairments. A known prominent inhibitor of IKKb/NF-kB signaling is the dietary flavonoid butein. We initially determined that oral, intraperitoneal, and intracerebroventricular administration of this flavonoid improved glucose tolerance and hypothalamic insulin signaling. The dosedependent glucose-lowering capacity was profound regardless of whether obesity was caused by leptin deficiency or high-fat diet (HFD). To confirm the apparent
central role of IKKb/NF-kB signaling in the control of glucose and energy homeostasis, we genetically inhibited this pathway in neurons of the arcuate nucleus, one key center for control of energy homeostasis, via specific adeno-associated virus serotype 2–mediated overexpression of IkBa, which inhibits NF-kB nuclear translocation. This treatment attenuated HFD-induced body weight gain, body fat mass accumulation, increased energy expenditure, and reduced arcuate suppressor of cytokine signaling 3 expression, indicative for enhanced leptin signaling. These results reinforce a specific role of central proinflammatory IKKb/NF-kB signaling in the development and potential treatment of DIO-induced comorbidities.