Sometimes I wish I were Michael Phelps: It would be really nice to be required to eat at least 7000-8000 calories per day so as not to lose weight.
For those who aren't record-breaking, calorie-torching machines - also known as the rest of society - obesity is a growing problem (no pun intended).
Approximately one-third of all adults in the U.S. are considered obese, which means to have a body mass index greater than 30 kilograms per square meter. Obesity has been linked to increased rates of type 2 diabetes, cardiovascular disease, osteoarthritis and certain types of cancers.
In response to this epidemic, researchers at the Hopkins School of Medicine and the School of Public Health have discovered how two compounds work together to prevent weight gain in mice that were fed a high-fat diet.
The first compound, a synthetic fatty acid known as CDDO-Im, works by activating the second compound, Nrf2. Nrf2 regulates the expression of genes by determining whether or not certain portions of DNA are read and translated in the nucleus.
Previous studies have shown that CDDO-Im prevents the accumulation of lipid droplets through a mechanism that is dependent on Nrf2, and that it also inhibits the production of fatty acid-generating proteins.
However, though these results have been shown in a petri dish, the Hopkins researchers wished to test whether CDDO-Im was capable of functioning as an anti-obesity drug in mice that were fed a high-fat diet, and if it were, to find the mechanism behind it.
To test the first hypothesis, the scientists compared the weight gain in two groups of mice. One group was genetically normal, and the other had the gene that codes for Nrf2 disrupted. When mice on a normal diet were treated with CDDO-Im, there was a slight decrease in weight gain in the Nrf2-disrupted mice.
However, when the Nrf2-disrupted mice were fed with a high-fat diet, CDDO-Im did not inhibit weight gain at all, and the mice became obese.
To determine the mechanism behind CDDO-Im, researchers also investigated the energy expenditures of mice on the drug, and found that it caused mice to consume greater amounts of oxygen and expend more energy, contributing to the prevention of weight gain.
Interestingly, the mice with Nrf2-disrupted genes had lower body mass before being given a high fat diet and treated with CDDO-Im, compared to those with normal copies of the gene.
However, after being fed high-fat diets, the Nrf2-disrupted mice experienced significant weight gain. This suggests that normal Nrf2 levels may lead to weight gain when fed a high-fat diet but not when treated with CDDO-Im.
By demonstrating this correlation between obesity and Nrf2, Nrf2 could become a molecular target for potential treatments in obesity management.
