January 11, 2013
NIH Podcast Episode #0177
Balintfy: Welcome to episode 177 of the new NIH Research Radio. The new NIH Research Radio is your source for weekly news and information about the ongoing medical research at the National Institutes of Health – NIH . . . Turning Discovery Into Health®. I'm your host Joe Balintfy, and coming up in this episode our news summary at the end of the program includes items on
- newly discovered genetic factors for Bechet’s disease
- a gene that impacts the clearance of hepatitis C, and
- new details on the early stages of muscle formation and regeneration
But first, our feature story: understanding metabolism.
Balintfy: If you tuned into episode 175 of NIH Research Radio, you heard about my experience participating in a clinical trial, which included 23 hours in a metabolic chamber – basically an air-tight room that measured how much energy I burned. At the same time I was in one room for the Narcolepsy study I participated in, there were volunteers in an adjacent chamber helping researchers understand how temperatures affect our metabolism. The principal investigator for that study is Dr. Kong Chen. I’m talking with Dr. Chen today about metabolism and first, I want to ask, what’s a good way to define metabolism and our metabolic system?
Chen: The general sense of metabolism is how many calories you burn at what rate so that’s also called energy metabolism. But sometimes people use metabolism quite generally like the metabolism of drugs, you know, how quickly a drug is cleared out of your system but that’s drug metabolism. So sometimes those two terms get mixed up and the metabolic system if you will is essentially the term defines for example the whole body as a metabolic system uses calorie or a specific system like the liver uses a certain fuel. So that’s where it differentiates.
Balintfy: So you’re studying the metabolism and how it can be controlled, right? Can you tell me a little bit about what you’re studying?
Chen: Yes. So what we’re trying to understand is how the metabolism, individual’s metabolism is regulated. We know quite well that typically your metabolic rate or your metabolism is associated with your body size and specifically is associated with your body composition. So that’s to say that if you have more organ mass or muscle mass and/or muscle mass you typically have a higher metabolism versus someone that’s smaller, have less of lean mass, that has a less or a slower metabolism, that’s typically but there’s individual variabilities to that. So for example, you and I may have the same amount of muscle mass, same amount of at mass, but you could have a little bit higher metabolism than I do. Now for that we don’t understand to the entire range why that is so.
Then another phenomenon that we’re very interested in is that is not static. Meaning that at a normal temperature for example the temperature we’re in probably around 23 degrees C or 72, 73, that our metabolism are very similar and very comfortable. But change that temperature to 65 or 68 degrees Fahrenheit then our metabolism could be dramatically different. Meaning that we regulate our metabolism slightly different and then what determines that and how to control that is what we’re interested in.
Balintfy: And you’re also interested in the implications of that if the metabolism is working differently in colder or hotter temperatures, right?
Chen: Absolutely. So we know that humans are not static. We are designed to be dynamic. We’re designed to be adaptive to what an environment throws at us. Of course now, most of the room temperature, car temperature, shop temperature wherever you go pretty much unless you’re outside, you’re pretty well regulated and in a tight range thanks to our advancement in air conditioning, heat, and whatnot. But perhaps that’s contributing to some of our problems in terms of obesity. We don’t know the cause and effect of that, but it certainly has a trend to that. Because we know that our body has sort of set point if you will of comfortable temperature, what we call thermal neutral zone and that’s right around the range that we feel comfortable and it’s likely the fact that we control the temperature in that range. Whereas below that range, we have a higher metabolic rate needed to balance out the heat loss and above that zone, also our metabolic rates are also higher because to compensate for the sweating and everything else. So we constantly push ourselves into a very low metabolic range, consciously or unconsciously. So that may have implication to how we control our body weight.
Balintfy: So temperature is one way that that metabolic rate and perhaps body weight can be altered. What other ways does a person’s metabolic rate change Dr. Chen?
Chen: Very good question. So if you look at a metabolic rate in general, 24 hours or there are some major factors, one is a resting component. You know, if you can subdivide that rest into sleeping, that’s your lowest metabolic rate, okay. Rest is defined as early in the morning, awake, fasted, lying supine, not doing much. Okay. So that people are found to be slightly higher than sleeping and the difference between the two, between the resting and sleeping, some people call that arousal okay. And so the resting metabolic rate as a standard measurement, people can do it in a short term using a metabolic hood and that encompasses about 60%-70% of your total energy expenditure.
The other 30 or so percentage, highly depend on two factors. One, how much do you eat. So it turns out it’s not very well understood but there is a small component between 8%-12% of your metabolic rate during the day is used for digesting food, transporting the food stored. Some people call the thermal effect food, some people call it diet induced thermogenesis. Nevertheless, that’s a component that’s obligatory that obviously you need.
Then there’s a component called sort of adaptive thermogenesis and that’s a general sense for anything that regulate your basic movement, maintain your posture or some things, spontaneous movement like I’m moving my hand as I’m talking to you and just maintain your basic function. Above and beyond that is volunteer control for example exercise, movement, catch a bus, that type of movement related energy expenditure and that component is the most variable. It can vary from very little if you’re not doing much that day or if you go off for a long run that can double the amount or triple. So for example athletes being measured for Tour de France for example, they can burn up to 10,000 calories per day while they’re riding, but on a rest day they use very little amount of energy. So that gives you a human dynamic range.
Balintfy: So there’s a different metabolic rate for when I sleep or when I just rest, when I digest food, when I move around a little, and when I exercise. And you mentioned, our metabolic rate also changes when we get out of that comfort zone of about 23 Celsius or 73 Fahrenheit. Now what can I do with that information? Is there something in what you’re studying that I can take home? If I lower the temperature of my thermostat at home or in my office, am I going to burn more calories, is that going to help me burn off the holiday meals and deserts I recently ate? Basically, what are the practicalities that you see coming out of this research?
Chen: That’s the golden question. Obviously, as a scientist, we like to understand how our body work and how our bodies are different from each other therefore we can sort of define a window of potential interventions. That’s sort of the basic research we do. In the other sense of course, we want to provide information to the subject participants how they can use that. For example, a lot of our subject who comes in are very curious how many calories people burn. You know, as the society, we’re very interested in knowing how many calories we’re taking in and why can’t I lose weight or why can’t I gain weight. The reverse question is also true sometimes.
So when we explain the basic sense of energy balance is in and out and then people want to know well how many calories do I really use, how many calories do I need for certain circumstances for example at rest or at sleep. Can I increase the metabolism and so for all we know right now there are not too many medications that can increase their metabolism. A lot of the anti-obesity drugs are for controlling eating, control appetite but part of the problem is that that by and large affects the central nervous system and therefore some of the really bad side effects is extended from this central effect of these drugs. Wouldn’t it be nice if we can target something that is peripheral and increase metabolism without influencing diet? Now that’s a big question but that’s what we’re going after.
Balintfy: How do you study that? How do you measure metabolism?
Chen: So to measure metabolism, you can do one of two ways. It used to be the way you have to measure heat so that’s called direct calorimetry. So you can put someone in the room, if you can close that room with metal walls so all the heat dissipated by the human body gets absorbed into the metal wall and you can then circulate the metal wall outside with water, you can measure the temperature change of the water. Now that method is rarely used nowadays. It still is in one or two labs for measuring specific heat related issues like heat stress and whatnot.
What we do is called indirect calorimetry. So we measure the oxygen intake and CO2 production. So for the same person in a small room, we circulate the room with fresh air and then we measure the oxygen and CO2 content of that air before it goes in and after it comes out. The difference is what the subject breathes. So from that, we can calculate exactly how many calories in that minute or two is essentially being expended. Because that traces back to the fuel you use which is carbohydrate and/or fat and it’s a little bit of protein. So we are very good at measuring tiny traces of oxygen and CO2.
Balintfy: A person that’s going to their primary care physician probably isn’t going to get their metabolism measured though, are they?
Chen: Not very likely.
Balintfy: If they were curious enough to know about that, is there an opportunity for them to participate in the clinical trial?
Chen: Absolutely. Absolutely. There are only a few metabolic facilities around the country that does this detailed measurement of metabolic rate and these are essentially called metabolic chambers. There are easier way to measure resting metabolic rate and this is done classically using a plastic hood, put it over your head for 30 minutes or so but that can only be done in short periods and typically at rest. We do that standardly for clinical patients but for research purposes, this metabolic room can continuously measure for over a period of time and for hours into two or three days. So the advantage of the latter is that you can find out the dynamic change between different conditions, for example different temperatures or different meal conditions or different exercise conditions, continuously.
Balintfy: You said there aren’t very many places that have metabolic facilities. How many do we have here at the NIH?
Chen: So we have three metabolic rooms and we call them suites and they are the biggest metabolic chambers if you will because that’s the technical term and there are only a few sites that have multiple rooms. So we can actually increase our throughput of these studies and do it simultaneously. So there are about 12 centers around the country have metabolic rooms and only four of them have multiple rooms. So we’re lucky to have three rooms that are operating at the same time.
Balintfy: So they can be used for a variety of study, I was in a narcolepsy study.
Chen: That’s true. A lot of them do other type of research. So for example, there are rooms that are being used to specifically set up for sleep studies and there are other set up to do clinical to do clinical trials one of them you probably don’t want to put on the radio. They’re doing deep brain stimulations and how they affect metabolism but that’s a different story.
Balintfy: Ok so back to the basic metabolism questions Dr. Chen. Can you explain more about how different people might have a different metabolic rate? You mentioned that Tour de France cyclist who can burn 10,000 calories while they’re riding. I would have thought an athlete like that would have a different metabolic rate no matter what they’re doing.
Chen: So that is a good hypothesis but so far, we’ve found, we’ve studied many people – in my career, I’ve probably measured over a thousand people from very elite athletes, we’re talking about some basketball players in the collegial level that women have 5% to 6% body fat, which is lower body fat than most male athletes just sort of conventional athletes, and to very obese people – when you actually put them all in the same chart and compare their resting metabolic rate at a thermal neutral condition versus their body composition, they fairly fall closely on the same line. Meaning that they may be very different in terms of body size, body shape, fitness level, but when you calculate into the fact the body composition difference, their metabolism at rest are quite similar. Now, their efficiency maybe very different.
Balintfy: And what about a connection between metabolism and obesity, is there one?
Chen: There is some connection between metabolism and obesity, but the direction of that is not what typically people understand. So a classic misunderstanding or myth if you will is that people who are obese have lower metabolism. In fact, what I was trying to explain that people typically if they are bigger, they actually have higher metabolism because obese people actually have higher lean body mass as well in fact. So by absolute values, they have a higher metabolism than someone that’s smaller. But if you put them on the same chart in terms of gradually increasing body size, their metabolism gradually change to be higher as well. So the sort of myth of obese people have a lower metabolism is generally not true.
Now in my experience, we have measured people who are outside the normal range. There are a few people that are lower metabolic rate for their body size and there are some lean people and there are some obese people for that. I mean that maybe genetically determined.
Balintfy: And is there a way to know which came first? Is it because they have a lower metabolism that they have that body type or is it because they have that body type that they have that metabolism?
Chen: That is a very good question and there are some longitudinal studies have shown both effect. So there’s a classic study done in Pima Indians that have shown that people who are outside their normal range particularly with the people with a lower metabolism for their body size had gained more weight years later. But that study was very difficult to replicate in other populations. So it’s typically thought that it’s the lower – the higher metabolism is secondary to weight gain or obesity rather than other way around.
Balintfy: How did this Pima Indian study work and can you explain more about what it has shown?
Chen: The Pima Indian study has been a historically very important study. The Pima Indians are the ones that are being studied by our colleagues at NIDDK in the Phoenix branch. The Gila River Pima Indians they live just outside Phoenix area and I need to check my dates but I think starting in 1960s, it was observed that they have a tremendous amount of high incidence of both obesity and diabetes. So NIDDK set up a remote site to specifically study the genetic and environment of this group and some of our esteemed colleagues are still doing that following these people from the very beginning when they were born. In fact now they’re studying pregnancy and follow their infants along. It’s been shown both genetic and environment reasons have high propensity for gaining weight and also develop into type 2 diabetes early.
A really nice work, line of work have shown the comparison between the Pima Indians how live in the Phoenix area versus their related cousins or close family members live in Mexico under the very traditional living, which they plant their crops, eat off their fields and their rates of obesity and diabetes have really been low so suggesting a strong environmental influence not just only genetic.
Balintfy: Dr. Chen, back to your research on temperature and metabolism, what else would you highlight?
Chen: Yeah. So the other thing that you know going a little bit deeper on our research topic is in fact it is surprisingly to us that how our body regulate metabolism in a wide temperature range, there’s very little data that we know of. The only data with multiple temperature points with the metabolism that we’re aware of is back in the 1930s and 1950s and that was studying the direct calorimetry rooms by two very famous scientists and they’ve done experiments on themselves.
We certainly don’t have any data on obese and considering our society now 67% of overweight and obese population and we don’t know if that extra layer of insulation changed the basic physiology of how our body regulate temperature and how our body regulate metabolism. So one of our major goal for this study is to actually not only study normal lean healthy young males, your typical normal studies is inclusive of, but we’re actually going to look into how obesity confound our physiology. So we’re going to be comparing obese males to lean males of the same race and ethnicity then we’re going to study aging, how aging itself affects our metabolism and control our body temperature. In fact that’s been sort of suggested as we get older, we have a different cold tolerance. Is that really changing our metabolism per se? We don’t know.
How women are different than men and how women in different menstrual cycles maybe are different in terms of their physiology and metabolic physiology. So that’s all in the area that we’re trying to look at and ethnicity. Is African-American different than Caucasians in terms of this kind of relationship.
Balintfy: It looks like a lot of study ahead.
Chen: Yes. Exciting. But our next stage is we study – our first stage is we have looked at lean, healthy males, young males and now this next stage, we’re really trying to fill out our gaps in many of this area. Our next question is really to look at obese individuals.
Balintfy: Thanks to Dr. Kang Chen at the NIH’s National Institute of Diabetes and Digestive and Kidney Diseases. For more information on his research, visit www.niddk.nih.gov. And to see about participating in a clinical trail, visit www.clinicaltrails.gov or ClinicalResearchTrials.nih.gov. And coming up, those news stories about Bechet’s disease, hepatitis C, and muscle formation and regeneration. That’s next on NIH Research Radio.
(BREAK FOR PUBLIC SERVICE ANNOUNCEMENT)
Balintfy: Now for some recent news headlines from NIH, here’s Craig Fritz.
Fritz: Researchers have identified four new regions on the human genome associated with Behcet's disease, a painful and potentially dangerous condition found predominantly in people with ancestors along the Silk Road, an ancient trading route linking the Far East with Europe. Behcet’s disease is triggered by complex genetic and environmental factors, and causes inflammation of blood vessels in various parts of the body. Common symptoms include painful mouth and genital sores, and eye inflammation that can lead to blindness. In some cases, it can be life-threatening, affecting blood vessels in the brain, lungs, and other vital organs. The current study makes a case for a connection between Behcet’s disease and disorders such as psoriasis and inflammatory bowel disease, and raises hope that some of the treatments that have been found effective in those illnesses will have some utility in Behcet’s disease.
NIH scientists have discovered a gene that interferes with the clearance of hepatitis C virus from the body. They also identified an inherited variant within this gene that predicts how people respond to treatment for hepatitis C infection. Chronic infection with hepatitis C virus is a cause of liver cirrhosis and liver cancer. Up to 80 percent of people who are acutely infected with hepatitis C fail to clear the virus and develop chronic hepatitis C infection. Researchers believe this gene discovery offers a new target for therapies aimed at hepatitis C and other diseases.
Researchers at NIH have uncovered details of the early stages of muscle formation and regeneration. They identified proteins that allow muscle cells in mice to form from the fusion of early stage cells. The findings have implications for understanding how to repair and rehabilitate muscle tissue and to understanding other processes involving cell fusion, such as when a sperm fertilizes an egg, when viruses infect cells, or when specialized cells dissolve and assimilate bone tissue in order to repair and maintain bones.
For this NIH news update – I’m Craig Fritz
Balintfy: You can get more information on these news items at www.nih.gov/news.
Balintfy: And that’s it for this episode of the new NIH Research Radio. Please join us again next Friday, January 18 when our next edition will be available. Coming up in that episode…
If we can understand sort of the details of infant’s visual exploration, we can identify the situations that might be most beneficial for learning.
Balintfy: If you have any questions or comments about this program, or have a story suggestion for a future episode, please let me know. Send an email to NIHRadio@mail.nih.gov. Also, please consider following NIH Radio via Twitter @NIHRadio, or on Facebook. Until next week, I'm your host, Joe Balintfy. Thanks for listening.
Announcer: NIH Research Radio is a presentation of the NIH Radio News Service, part of the News Media Branch, Office of Communications and Public Liaison in the Office of the Director at the National Institutes of Health in Bethesda, Maryland, an agency of the US Department of Health and Human Services.
About This Podcast
Spokesperson: Dr. Kong Chen
Topic: metabolism, metabolic, metabolic rate, resting metabolism, energy, calories, body, muscle, fat, obese, obesity, weight, temperature, gene, genetic, Bechet, Bechet’s disease, hepatitis, hepatitis C, muscle, muscle mass, muscle formation, muscle regeneration