Environmental Factor, August 2011, National Institute of Environmental Health Sciences
Using nutrition to alter host susceptibility to environmental toxicants
In response to a question by NIEHS/NTP Director Linda Birnbaum, Ph.D., about whether early life PCB exposure would predispose for development of diabetes and cardiovascular diseases, Hennig said, “There is lots of interest in looking at this, and experiments are underway.” (Photo courtesy of Steve McCaw)
Heather Henry, Ph.D., program administrator for the NIEHS SRP, was host of Hennig's seminar. She listened intently to his argument that nutrition interventions can pave the way for developing primary prevention strategies of diseases associated with many environmental toxic insults. (Photo courtesy of Steve McCaw)
NIEHS SRP founder and Director Bill Suk, Ph.D., joined Hennig following the presentation. As Suk commented at an earlier workshop at UK in January 2011, “It's clear that nutrition can be a potential modulator of diseases that have been associated with exposure to environmental stressors, and this interplay will have important implications in risk assessment.” (Photo courtesy of Steve McCaw)
As part of the Superfund Research Program (SRP) Distinguished Lecturer Series, nutritional toxicologist Bernhard Hennig, Ph.D.(http://cvrc.med.uky.edu/users/bhennig) , of the University of Kentucky (UK), discussed ways to attenuate vascular endothelial cell dysfunction induced by exposure to polychlorinated biphenyls (PCBs) during a seminar July 14 at NIEHS. Hennig offered a compelling argument for using nutritional modulation of environmental insults in vasculature-related diseases and educating people about ways to improve their nutritional status.
"Nutritional interventions may provide the most sensible means to develop primary prevention strategies for diseases associated with many environmental toxic insults,” Hennig maintained, including such major public health concerns as atherosclerosis and type 2 diabetes.
Building on this nutritional paradigm, Hennig advocates for what he calls “a mindful nutrition,” including healthy diet and a regular exercise routine, as key to countering the effects of genetic predisposition to disease and exposure to environmental pollutants. Although people can't control their genetic makeup and aren't always aware of toxicants in their environments, Hennig said, “We can control our lifestyles.”
Hennig is the director of the SRP-funded Nutrition and Superfund Chemical Toxicity (NSCT) program(http://www.uky.edu/Research/Superfund/) at UK, which manages biomedical and environmental engineering projects that interact with the research translation core for community outreach and education. The program's community engagement activities include translating nutrition research to public with registered dietitians - promoting a healthy diet of more fruits, vegetables, fiber, and low-fat foods to boost immune system, as well as more physical activity.
PCBs and atherosclerosis - What are the mechanisms?
As Hennig explained, research at the NSCT program showed that PCBs induce adipocyte differentiation and expression of proinflammatory cytokines in adipocytes. In addition, in experiments with mice, PCBs promote glucose and insulin intolerance associated with dysregulation of cytokine messages and protein levels. Only recently, however, have researchers established that PCB exposure also contributes to vascular diseases, showing that persistent organic pollutants, such as PCBs, can lead to cardiovascular toxicity and atherosclerosis.
Arylhydrocarbon receptor (AhR) and its subsequent activation by AhR ligands, such as coplanar PCBs, mediate gene expression in the nucleus that generates reactive oxygen species (ROS) and thereby induces expression of proinflammatory cytokines, including interleukins (IL), nuclear factor kappa-light-chain-enhancer of activated B cells (NF-kB), and vascular cell adhesion protein (VCAM). In doing so, AhR ligands are atherogenic and disrupt barrier functions of endothelial cells by increasing transendothelial flux in blood vessels.
Hennig also explained that caveolin-1 (cav-1) was found to be a culprit in exacerbating PCB-induced inflammatory responses. PCB exposure leads to upregulation of cav-1 protein expression. Cav-1 binds AhR in co-immunoprecipitation assay, and PCB exposure magnifies this interaction.
Nutrition as a preventive measure against environmental chemical toxicity
Hennig's laboratory showed that omega-3 polyunsaturated fatty acids block PCB-mediated oxidative stress, and downregulate inflammation in both cell culture studies and in animal models. In contrast, omega-6 fatty acids, found in many edible fats, such as corn or safflower oils, amplify PCB-induced inflammation and, even by themselves, induce lower-grade inflammation. In addition, flavonoids, such as quercetin polyphenols, block PCB induction of cav-1 protein expression.
Hennig explained that it's difficult to specify the optimal amount of omega-3 intake, but he suggested that a close to 1 to 1 ratio of omega-6 to omega-3 is very good. “The [typical] American diet is composed of about a 10 to 1 ratio of omega-6 to omega-3,” said Hennig.
Hennig also noted that he is exploring the potential of cav-1 as a biomarker for diagnosis of atherosclerosis induced by environmental pollutants. He said the use of tissues or body fluids for this screen is currently under investigation.
(Emily Zhou, Ph.D., is a Research Fellow in the NIEHS Laboratory of Signal Transduction Inositol Signaling Group.)
Community awareness and education
Hennig and his NSCT program staff work together to pinpoint the science behind the interplay among environmental toxins, nutrition, and disease. They are also dedicated to raising the public awareness of their research results in their communities. Their projects are nicely integrated with their Community Outreach and Research Translation Cores, which have reached out to numerous communities, including ones near PCB-contaminated Superfund sites in Paducah and Harlan County, Ky., to educate residents about the importance of diet for overall health and protection against the harmful effects of exposure to pollutants. NSCT, Hennig said, also collaborates with the state's Cooperative Extension Service, which is also based at the university.