A magic pill for controlling obesity is a dream that many have. Researchers exploring human metabolism at the University of California, San Francisco, have uncovered a handful of chemical compounds that regulate fat storage in worms, offering a new tool for understanding obesity and finding future treatments for diseases associated with obesity. Such compounds may allow chemical control of obesity. As described in a paper published this month in the journal Nature Chemical Biology, the team took armies of microscopic worms called C. elegans and exposed them to thousands of different chemical compounds. Giving these compounds to the worms, they discovered, basically made them skinnier or fatter without affecting how they eat, grow, or reproduce.
Obesity is a medical condition in which excess body fat has accumulated to the extent that it may have an adverse effect on health, leading to reduced life expectancy and/or increased health problems.
Obesity increases the likelihood of various diseases, particularly heart disease, type 2 diabetes, breathing difficulties during sleep, certain types of cancer, and osteoarthritis. Obesity is most commonly caused by a combination of excessive dietary calories, lack of physical activity, and genetic susceptibility, although a few cases are caused primarily by genes, endocrine disorders, medications or psychiatric illness. Evidence to support the view that some obese people eat little yet gain weight due to a slow metabolism is limited; on average obese people have a greater energy expenditure than their thin counterparts due to the energy required to maintain an increased body mass.
Dieting and physical exercise are the mainstays of treatment for obesity. Moreover, it is important to improve diet quality by reducing the consumption of energy-dense foods such as those high in fat and sugars, and by increasing the intake of dietary fiber.
To supplement this, or in case of failure, anti-obesity drugs may be taken to reduce appetite or inhibit fat absorption. In severe cases, surgery is performed to reduce stomach volume and/or bowel length, leading to earlier satiation and reduced ability to absorb nutrients from food.
The new discovery gives scientists new ways to investigate metabolism and could eventually lead to the development of new drugs to regulate excessive fat accumulation.
The work also demonstrates the value of worm screening as a way of finding new targets for human diseases, according to the UCSF scientists, whose work was spearheaded by postdoctoral fellow George Lemieux, PhD, in the laboratory of Professor Zena Werb, PhD, vice chair of the Department of Anatomy at UCSF.
The UCSF team’s interest in how worms deal with fat began with a more fundamental interest in human metabolism. Worms make molecules of fat for the same reasons humans do — they are useful for storing energy and are a basic building block for body tissues. Many of the genes and mechanisms worms use to regulate fat accumulation have similar systems in humans, and not all of them are completely understood.
Starting with 3,200 different chemical compounds and 3,200 pools of tiny worms, the UCSF team used a red dye that sticks to fat molecules to pinpoint under the microscope which of the chemicals made the worms fatter (more red) or skinnier (less red). They identified a few dozen, and performing additional tests, narrowed in on about 10 compounds they believe regulate fat metabolism. Those compounds not only altered fat storage in the worms but in insect and human cells grown in test tubes, leading Lemieux to comment that they may be useful for understanding metabolism in other organisms.
The real strength of the work may be in that it demonstrates the value of the new worm screen over existing screening tools for identifying the genes, proteins and other molecular players involved in human health.
A large part of drug discovery involves identifying these players and designing ways to treat diseases that emerge when they don’t work correctly. But identifying the targets is only the beginning. Designing a effective drug takes many years of testing and evaluation. What works well on a test tube or lab scale may not work at all when applied to the body.
The value of the worm screen is that it allows scientists to select potential compounds for further study.
For further information: http://www.universityofcalifornia.edu/news/article/25204