Good fat is in a war with bad fat. And the key is to keep your body's metabolic balance from shifting due to a missing protein called p62. But is p62 missing from your body? What's new in the study of normal fat metabolism? Scientists found that when good 'brown' fat is fighting bad 'white' fat, it may cause the human body's metabolic balance to shift.
When a protein called p62 is missing, the enzyme p38 is less active in brown fat and an enzyme called ERK is more active in white fat, making p62 a master regular in normal fat metabolism. Sanford-Burnham Professors Jorge Moscat, Ph.D., and Maria Diaz-Meco, Ph.D. co-authored a study on p62's role in fat metabolism.
The researchers showed that protein p62 balances metabolism in fat tissue. Does the study present a target for anti-obesity therapies such as more drugs to be developed? Or does it open doors to find the real, root causes of what balances or unbalances fat metabolism in people and animals such as eating diets that tend to unbalance a body's fat metabolism for those predisposed? For example, lifestyle and eating habits are taking a heavy toll on the rural Chinese diet now that coffee has become more popular instead of green tea and Western fast foods have gained in popularity. See, China's Growing Obesity Problem | Photos - ABC News.
For example, in China more vegetables mean frying them in oil in a wok, and more fat in the diet. Vegetables aren't eaten raw in salads or even steamed in most cases. See, Are Vegetables and Exercise Causing Childhood Obesity in China? Besides sedentary behavior such as sitting at computers all day or playing video games and watching TV, kids introduced to more vegetables are eating them deep fried in fat or stirred in oil. Two most common methods of preparing vegetables is deep-frying and stir-frying in China as well as in areas of the USA. Kids are not getting more raw kale salads topped with chopped vegetables such as cilantro, carrots, and tomatoes or even chopped raw apples.
In China, as in other countries, more educated parents, who are likely also richer, may be able to afford fast food, which is cheap in America but not so much in developing countries. Also, overweight children may be underreporting their intake of unhealthy food and may misperceive the quality of the exercise they do, according to the article, Are Vegetables and Exercise Causing Childhood Obesity in China?
But in a new study in the USA, on what may cause obesity and what therapies may help in the future, researchers found that the protein p62 blocks the action of an enzyme called ERK while activating another enzyme called p38. When p62 is missing, the enzyme p38 is less active in brown fat, while the enzyme ERK is more active in white fat. As a result, the protein called p62 is “a master regulator” in normal fat metabolism. What you want in your body is to make sure you are not missing a master regular of fat metabolism so your bad white fat doesn't overtake your good brown fat that burns calories.
At least that's what happened with mice in a new study, which also happens to be a theory about about what causes the body to store more fat and burn less energy in obesity. The important role played turns out to be a protein called p62. If the protein p62 is missing, you have a turn for the worse when it comes to keeping metabolism normal and in balance for an individual--or at least for the mice in the study. According to the new study from the Sanford-Burnham Medical Research Institute which is published in the December 21, 2012 issue of the Journal of Clinical Investigation, when this protein called p62 is missing in fat, the body's metabolic balance shifts.
What happens is that the human body inhibits "good" brown fat, while favoring "bad" white fat. These findings indicate that p62 might make a promising target for new therapies aimed at obesity. Most studies are done with a goal of not only finding what happens next and how, but with the result of developing new therapies for a solution to the problem. But as a study, readers need to take in mind that the researchers at Sanford-Burnham Medical Research Institute have a new theory. And the study of their theory has been funded by the This study was funded by the National Institutes of Health, the National Institute of Allergy and Infectious Diseases grant DK088107, and the National Cancer Institute grants CA132847 and CA134530. You can read the abstract of the original study, See, "p62 Links β-adrenergic input to mitochondrial function and thermogenesis" - Journal of Clinical Investigation.
The secret is a protein called p62
Sanford-Burnham Professors Jorge Moscat, Ph.D., and Maria Diaz-Meco, Ph.D. co-authored a study on p62's role in fat metabolism
Sanford-Burnham researchers show that protein p62 balances metabolism in fat tissue—making it an attractive target for anti-obesity therapies, according to the January 4, 2012 news release, "Shifting the balance between good fat and bad fat."
In many cases, obesity is caused by more than just overeating and a lack of exercise. Something in the body goes haywire, causing it to store more fat and burn less energy. But what is it? Sanford-Burnham researchers have a new theory—a protein called p62. According to a study the team published December 21 in the Journal of Clinical Investigation, when p62 is missing in fat tissue, the body’s metabolic balance shifts—inhibiting “good” brown fat, while favoring “bad” white fat. These findings indicate that p62 might make a promising target for new therapies aimed at curbing obesity.
“Without p62 you’re making lots of fat but not burning energy, and the body thinks it needs to store energy,” said Jorge Moscat, Ph.D., Sanford-Burnham professor. “It’s a double whammy,” according to the January 4, 2012 news release by Bruce Lieberman, "Shifting the balance between good fat and bad fat." Moscat led the study with collaborators at Helmholtz Zentrum München in Germany and the University of Cincinnati.
p62 and obesity
Moscat’s team had previously produced mice that completely lack the p62 protein everywhere in their bodies. As a result, the animals were obese. They also had metabolic syndrome. In other words, as compared to mice with p62, mice lacking p62 weighed more, expended less energy, had diabetes and had a hyper-inflammatory response that’s characteristic of obesity.
While those results showed that the lack of p62 leads to obesity, “we didn’t know which tissue was responsible for these effects, because p62 was missing in all of them,” Moscat explained in the news release. Now the question for some researchers is whether that muscle tissue, where energy is expended, controls obesity?
Brown fat burns calories and white fat is unwanted body fat that builds up
Some scientists think that the liver is a key player, or that the brain’s appetite control center is most responsible for obesity. So far, the different theories need to be tested. On the other hand, there's there are white fat and brown fat. White fat is the type we think of as unwanted body fat. Brown fat, on the other hand, is beneficial because it burns calories. Many researchers now believe that brown fat somehow malfunctions in obesity, but the details are unclear.
In their latest study, Moscat and colleagues set out to pinpoint the specific tissue responsible for obesity when p62 is missing. They made several different mouse models, each missing p62 in just one specific organ system, such as the central nervous system, the liver, or muscle. In every case, the mice were normal. They weren’t obese like the mice lacking p62 everywhere, according to the news release by Bruce Lieberman, "Shifting the balance between good fat and bad fat."
p62 shifts the balance between white fat and brown fat
Researchers in this study 'designed' a mouse model lacking p62 only in the obese mice fat tissues. When the scientists observed the obese mice, the rodents were similar to the mice who were missing p62 in all their tissues. Upon further study, the researchers found that p62 blocks the action of an enzyme called ERK while activating another enzyme called p38. When p62 is missing, the enzyme p38 is less active in brown fat, while ERK is more active in white fat. As a result, Moscat said, p62 is “a master regulator” in normal fat metabolism.
Fat tissue is easier to reach than the brain when it comes down to drug therapies. After all, the studies usually are funded with a goal of developing more drugs to be used as therapy to solve issues when something in the body becomes unbalanced. Should scientists instead be looking for root causes to remedy in ways that don't always involve drug therapies? But that's where the fund money is coming from, to find new drug therapies for an issue, most people surmise. The question is whether scientists will design new therapies, new strategies, or new drugs or whether a change in nutrition or lifestyle will help those whose balance between white fat and brown fat gets unbalanced due to something in the body, in the genes, in the environment, in the food, or in the lifestyle.
According to Moscat, the discovery of p62’s role in brown fat tissue is encouraging, because fat tissue is much more accessible than other parts of the body—the brain, for example—for potential drug therapies. “This makes it easier to think about new strategies to control obesity,” he explained in the news release.
If the goal is to control obesity, scientists should also look at the root causes of obesity such as a drastic change in the way people eat and what they eat and how the food has changed over the centuries due to environmental and chemical changes in the soil and seeds, the way food is cooked, the way food is heated, or what people put on the food to extend taste.
New methods for preventing or treating obesity, a major epidemic in the United States, are urgently needed. Drug therapies designed to minimize the intake of food have had limited success and also produce considerable side effects.
People on diets know that in many cases diets don't work unless the diet and exercise plan is tailored to the genetic and metabolic signature and expression of the individual. It's about how the body responds metabolically and why it does so at the root cause rather than only at the symptom level. For further information, also check out the site, GMDI - Genetic Metabolic Dietitians International.
Resources
Careers in genetic and metabolic nutrition
Emory Genetics Metabolic Nutrition Program -- ACTSI
NCBI Book online text, "Nutritional and Metabolic Diseases
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