Obesity has long been a global epidemic with an estimated 2.8 million people dying each year from associated complications. In addition to watching one's diet and exercise, advancements in science have created opportunities to treat obesity with medicine. However, none has ever been shown to be effective. From bariatric surgery to the latest diet super-pill, obesity remains a global health issue.
Research efforts to treat obesity have recently focused on the hormone leptin, discovered 20 years ago to be associated with feeling full after a meal. In healthy individuals, leptin has the ability to suppress food intake and reduce body mass. In obese individuals, there tends to be no effect. This is due to leptin resistance. Leptin resistance put up a barrier to leptin treatment in obese people that has yet to be taken down...until now.
A study from Harvard Medical School has recently shown that there is promise for treating leptin resistance, and thus obesity, using a small molecule that can increase leptin sensitivity. The molecule is an extract from the Thunder God Vine, an herb long used in traditional Chinese medicine to treat a variety of ailments.
Umut Ozcan, the leader of the study, along with his team, focused on finding small molecules that could increase leptin sensitivity using in silico screening. Once determining that the extract from the Thunder god vine was a winner, the team tested the extract, called Celastrol, on lean and obese mice. They focused on food intake, body mass, and leptin levels in lean mice, diet-induce obese mice, and genetically obese mice that are completely lacking in leptin. Their findings are giving new hope to drug companies waiting for the next big thing in diet pills.
As published recently in Cell, Ozcan discovered that Celastrol suppresses food intake, blocks the reduction of energy expenditure, and can lead to a 45% weight loss in obese mice. Celastrol successfully increased leptin sensitivity in the lean and obese mice, while having no effect on genetically obese mice, as expected. "We have been heavily focusing on this line of research in my laboratory and hope that this approach will help us to understand the mechanisms in nature that are leading to the development of obesity," Ozcan says. "In the end, my main goal is to see this research leading to a novel and powerful treatment for obesity in humans."
These results are good news to those looking for obesity treatment, and create a strong case to shift research to studying leptin sensitivity over leptin resistance. The initial outcome looks positive, and the extract seems to be harmless in mice and even showed additional positive effects after use, such as decreased cholesterol and improved liver function. There is, however, more work to be done. Even though Celastrol is a natural compound derived from the roots of the thunder god vine, there needs to be more testing on whether the plant is indeed safe to use in therapeutics. Little is known about potential toxins in the plant and toxic effect studies will be an important follow-up.
Sources: Cell, WHO, WebMD, phys.org
