Transcript

 

Derek Smith:

Hello and welcome to Baylor Connections, a conversation series with the people shaping our future. Each week we go in depth with Baylor leaders, professors and more discussing important topics in higher education, research and student life. I'm Derek Smith and our guest today is Dr. Ramon Lavado. Dr. Lavado is an Environmental Toxicologist and Assistant Professor of Environmental Science at Baylor. He recently coauthored an article in the Journal Toxicology of Applied Pharmacology highlighting the impacts of exposure to chemical compounds found in many consumer products. It's research that has applications for a lot of people, anyone who's a consumer. It's received a great deal of attention and we're pleased to have him on the program with us today. Dr. Ramon Lavado, welcome to Baylor Connections. Thanks so much for joining us today.

Ramon Lavado:

Thank you. Thank you for having me here and giving me the opportunity to talk a little bit about the research that we do a Baylor.

Derek Smith:

Well, Dr. Lavado, we'll spend the next 20 minutes or so unpacking what I just briefly highlighted, but to get us started could you give us a little bit more of an overview of the study and the findings that we're going to unpack?

Ramon Lavado:

Yeah, sure. So our study, it's specifically relating metabolic disease to environmental chemical exposure to certain compounds. So let me give you a little bit of background. It is well known that metabolic diseases linked to lipid dysregulation, like obesity, pose a significant threat to human health. For many years the paradigm for those kinds of conditions, like obesity, has been a simple function of energy intake versus energy expended. That is excessive fat consumption, excessive energy intake and lack of physical activity. However, scientists are currently identifying specific biomarkers, bio molecules that under the influence of different environmental factors appear to be involved in the onset of those kinds of diseases. We found that the exposure to certain chemical compounds that can be found in common used things, in pesticides, fungicides, in flame retardant used in, for example, food containers, plastic films, they are able to induce lipid accumulation in human cells. And it's pretty important since this study is among the few that report changes in cells and these specific lipids as a result of that exposure to those compounds.

Derek Smith:

You mentioned obesity is one example of lipid related diseases. What are a broader definition of lipid related diseases and what are other examples?

Ramon Lavado:

Yeah, so lipid related diseases, which are also known as lipid metabolism disorders, are alterations in the use and the storage of fat in the body. Lipids are fat or fat like sources. And if you have one of these disorders, you may not have enough enzymes to break them down, okay? Or those enzymes may not work properly and your body can't convert the fats into energy resulting in a harmful increase of lipids stored in your body. So over time that can damage your cells and tissues, especially in the brain, in the peripheral nervous system, in the liver, in the spleen. Many of these disorders can be very serious or sometimes even fatal. In fact, according to Mayo Clinic, obesity is defined as a complex disease involving an excessive or an excess of body fat. In our study we focus in liver tissue. The most common lipid related disease in that tissue is called NAFLD. That stands for nonalcoholic fatty liver disease and that's strongly related to obesity.

Derek Smith:

We are visiting on Baylor Connections today with Dr. Ramon Lavado, Assistant Professor of Environmental Science at Baylor. You mentioned a few examples of consumer products and where you find some of these chemicals that you're studying and their impact on obesity and other diseases. What should we know about those chemicals? How should we as consumers think about them and the things in which we find them?

Ramon Lavado:

Yes. In our study we use seven chemicals that can be found in those consumer products. So two pharmaceuticals, but we use them as a positive and negative control, those pharmaceuticals, we know what they do. We know the effects on lipid accumulation. So we don't take those into account. We use two chemicals used in plastics, two chemicals used as a polymer coating like nonstick cooking surfaces and one pesticide. So it's a broad variety of consumer products. We found that one of the plastic compounds, one that is commonly used in plastic films and one of the compounds used in coatings, nonstick surface coatings, that's really commonly... I think that if you go to your kitchen you will find that all your pans have those compounds, those are perfluorinated compounds. Those compounds contribute strongly to lipid accumulation in human liver cells.

Derek Smith:

As we look, Dr. Lavado, at this research, it might be helpful to know a little bit of background as we think about chemicals. How has usage of chemicals expanded over the years and the number of chemicals we might find that these products grown?

Ramon Lavado:

That's an interesting question. So the use of chemicals in human consumer products, is a clear example of exponential use. As of the year 2000 there were an estimated 100,000 commercially available chemicals around the world. And two decades later, by 2020, the amount has more than tripled. So it's approximately 350,000 chemicals being on a label and being used.

Derek Smith:

So it shows all the more the importance of this study. So just to highlight again as we talk more about the project itself, what were some of the specific questions that you were seeking to answer as you began?

Ramon Lavado:

Yeah, so I worked for years studying the interaction of chemical compounds with the endocrine system in humans and wildlife. The endocrine system is well known to play an essential role in regulating the metabolism and body weight. I found some studies that propose existence of endocrine disrupting chemicals. Those are compounds that they act like hormones with the potential to influence obesity, making them relevant to the obesity epidemic that we are getting worldwide. Those compounds were named obesogens. That's pretty interesting name. Previous studies have provided the strong evidence for the presence of those compounds in humans and animals. Those compounds were suggested to directly alter the function of metabolic organs controlling lipid homeostasis. So based on those studies, our study was designed under the hypothesis that the direct exposure of environmental obesogens will modify the lipids of liver cell by increasing total lipid accumulation and that's what we saw, not to all of the compounds. We should mention that half of them were presenting that, but that's a pretty impressive result. Even half of those compounds at environmental relevant doses were producing that effect.

Derek Smith:

How did you go about conducting that research? What did that look like if we were to have looked over your shoulder in the laboratory?

Ramon Lavado:

Yes, my laboratory, we use well-established techniques in molecular toxicology. We investigate in this study the proportion of different lipid related to diseases like obesity. And we do lipid profiles. We do a lot of chemistry, biology and in the mix between them, so a lot of mass spectrometry. We try to identify individual lipids and the changes that they happens in the human cells. That's pretty interesting. Also we use some visual techniques to see the cells. So I'm kind of old school molecular toxicologist and if I see only numbers and I don't see an effect in the cell, I'm kind of doubting. I want to see the cell alive and how my compound is modifying some kind of part of the cell. That's what we do with fluorosis microscopy. So those are the main techniques that we do in the lab.

Derek Smith:

How should we as individuals without maybe without the science background that obviously you have, how should we envision the cellular and metabolic effect that chemicals can have on our health? Is there an analogy or just a way that you would help the rest of us envision that?

Ramon Lavado:

Yes. I think that the significant increase that we saw of soft fatty acid, specifically diglycerides and triglycerides, those are the most common ones that when you go and get a blood test, those are the ones that they look for. You shouldn't get over certain levels and lower levels. So that's what we saw going up in the cells. In fact, medical studies, they pointed out that the hallmark for conditions like fatty liver disease is accumulation of those specific fatty acids. The chemicals that they can induce lipogenesis and contribute to fatty acid accumulation can be described, and it will be described as direct causes of lipid related diseases. And that's a direct proof of those diseases.

Derek Smith:

This is Baylor Connections. We are visiting with Dr. Ramon Lavado, Environmental Toxicologist and Assistant Professor of Environmental Science at Baylor. We're talking about an article he recently coauthored in the Journal Toxicology of Applied Pharmacology about the impacts of exposure to chemical compounds found in many consumer products. And Dr. Lavado, your study found that exposure to these compounds early in life was particularly meaningful. What impact did you find that early exposure to them had?

Ramon Lavado:

Yeah. Like any other chemical exposure, the earlier in life that exposure happens more harmful effects may happen in the adults. Those kinds of obesogens, they can act directly on cells by increasing the differentiation of adipocytes from STEM cells. That's important process in human growth. They can alter the number of those cells that store fat. They can modify and increase triglycerides and diglycerides storage in those cells, so they can modify the structure of those cells. In environmental toxicology, a key research breakthrough happened almost 30 years ago with a discovery and that sounds very impressive now, to believe in now, but we didn't know that before. So we discovered that children are far more sensitive than adults to toxic chemicals in the environment. This finally led to the recognition that chemical exposures early life are significant and preventable causes of diseases in children and adults. So in the cases of obesogens, this is not an exception. So early exposure to obesogens may alter seriously adult health and lipid metabolism and create and be the basis of some lipid related diseases.

Derek Smith:

So is it fair to say that it can help children be more likely to become obese as a child, but can also have more of a propensity to those other lipid related diseases as they get older as well?

Ramon Lavado:

Yes, that's one indication. And maybe that's another factor. As you know, obesity it's a disease that the causes are different factors. So the exposure to chemical compounds earlier in life, it's another factor that will contribute to those kind of obesity and lipid related diseases late in life.

Derek Smith:

We are talking with Dr. Ramon Lavado. And Dr. Lavado, as you discovered, as you did your research and did studies on the lipids in the cells, what work did you have to do to determine where they came from and to determine that, more specifically, they came from chemical compounds and not from other areas?

Ramon Lavado:

Yeah, so a lot of proportion of previous studies, they've been conducted in no human models. So they limiting their applicability to human biology. So we use a cell culture model system. We use liver cells that they were exposed to different compounds. So the cells are maintained in culturally media that has appropriate sources of energy and compounds, which regulate the cell cycle and divisions. And the media has sugars, amino acids, and lipids, so the lipids are already present there. So what those compounds are modifying is how the cells are using them or storing them, depending on the metabolism of those cells. In our case, the compounds, what they do, the effect that they have it's modifying the metabolism of those lipids, that they are present there in those in vitro system. In the cell culture systems we add lipids, of course, that they are there. In the human body they already present in the plasma. We got them from the food. So that's how they get the lipids.

Derek Smith:

Talking with Dr. Ramon Lavado. And Dr. Lavado, as we think about what you found in this study, what are some practical ways we can apply this knowledge? First, I want to ask you as the scientific community, how you apply it and then more specifically how we as consumers can apply it. So I'll ask you first, what are some ways that the scientific community can apply this knowledge?

Ramon Lavado:

Yeah, that's pretty interesting question for Environmental Toxicology. That's always our fight when he try to connect real exposure in the real world with effects. That's always going to be our weak point and it's hard to show that. In our case an important [inaudible 00:16:40] finding was that those effects were observed in cells exposed to chemical concentration that are often seen in the environment under which people are exposed constantly. We didn't expose the cells to humongous concentration of compounds. We exposed them to concentrations that you can find in the environment, in the water, in the fresh water, or even in food. So these results, they address understanding needs in the field of human health and toxicology by identifying key lipids and other metabolites that are altered as a result of exposure to environmental pollutants. I think I'm going to answer that question. The second question, they were [inaudible 00:17:27] like for scientific community for the regular public. So we are making this kind of research really relevant and our priority for regulatory toxicology programs and comprehensive chemical risk assessments with more human relevance.

Derek Smith:

Talking to Dr. Ramon Lavado. And now that you've found these, I think you just mentioned some, but I'll ask you again, what are some of the further questions that you want to pursue now that you have these findings? What other questions arise for investigation?

Ramon Lavado:

Yes, so I think that the next questions are easy. The first one will be to investigate the lipid accumulation in exposed cells using all the human models, like adipocytes, those are the cells that they accumulate fat, the endothelial and the skeletal muscle cells. The specific questions would be, are we going to be able to see the same effect on other cell types? If we see the same effect in endothelial cells, those are the cells of the blood vessels, is that contributing to cardiovascular diseases? And as a second main question, we'd love to investigate the mechanism of action of those compounds. What kind of receptors do they bind? What kind of metabolic pathways are they modifying? We see the effect in the cellular way, but we want to know how do they do that? So the answers to those kinds of questions may give us some therapeutic approaches for those kinds of lipid related diseases.

Derek Smith:

Dr. Lavado, on this work you had a number of students involved, people who researched, coauthored with you. What can you tell us about the way students were involved in the study and the important role they play? What's that like for you to engage them in that research?

Ramon Lavado:

Mm-hmm (affirmative). Yeah, so my group now, it's a small group. We have three grad students. I graduated one master student, so we were four, there were four. They are great. They did all the research, all the physical research, physical cell growing, and they improved methods on how to grow the cells, how to expose them. They do most of it. I just supervise. We had the idea in common. The main idea probably is coming from one of my projects and then they improve it. So it's great to work with the students. They are amazing. I think that 90% of the work of a lab is owned by the grad students. And undergrad students, of course, are always helping them.

Derek Smith:

Are there other research projects that you're working on that you are looking forward to in the weeks and months ahead?

Ramon Lavado:

Yes, my group is focusing on animal [tentatives 00:20:39] in Environmental Toxicology. That it the use of in vitro cell systems to evaluate toxicity. The classical toxicity studies are done by using the whole animal, whole fish, whole rats. In our case, we try to move away of the animal use. So we use cells. We have a few projects using fish cell lines, using even birth cell lines to avoid the use of the whole animals with different compounds. We are using human cells in this case to study those kinds of obesogen compounds. And we may move a little bit into using those kinds of in vitro systems to help human health. And now that we are in the coronavirus crisis, we are going to try to help to use those system to develop our vaccines or to develop new antivirals. So that's a different group of projects that we are working on.

Derek Smith:

Well, that's very exciting and you've already had an impact on human health through this study and we really appreciate you taking the time to share it. Dr. Lavado, thanks so much for joining us on the program today and good luck as you continue to share this research with different audiences and groups.

Ramon Lavado:

Again, thank you for having me. This year has been really interesting and unique. So thank you for having me here and giving me the opportunity to talk about my results. Thank you.

Derek Smith:

Absolutely, and a great example that the work goes on for so many of the other problems that we face. Baylor researchers continuing that research, even in the face of this broader coronavirus epidemic that we're facing. Thanks so much. Dr. Ramon Lavado, Assistant Professor of Environmental Science at Baylor, our guest today. I'm Derek Smith. A reminder that you can hear this and other programs online at baylor.edu/connections. Thanks for joining us here on Baylor Connections.