Results from a new mouse study suggest that elenolic acid, a natural compound found in olives, may lower blood sugar levels and promote weight loss. The research could pave the way for the development of safe, inexpensive natural products to manage obesity and type 2 diabetes in humans.
The researchers found that after just one week, obese diabetic mice given oral elenolic acid lost significantly more weight and had improved blood sugar (glucose) regulation compared with pretreatment and control mice that did not receive elenolic acid. The blood sugar-lowering effect was comparable to that of the injectable diabetes drug liraglutide and better than that of metformin, one of the most common oral medications for type 2 diabetes.
“Lifestyle modifications and public health measures have had limited impact on the rise of obesity, one of the biggest risk factors for type 2 diabetes. Currently available obesity medications are ineffective at maintaining weight loss, expensive and carry potential long-term safety risks. Our goal was to develop a safer, cheaper and more convenient multi-targeted drug that could prevent metabolic disorders and the development of type 2 diabetes.”
Dr. Liu Dongmin Professor, Department of Human Nutrition, Food and Exercise Sciences, Virginia Tech
Hana Al-Khalidi, PhD, a research scientist in Liu's lab at Virginia Tech, will present her findings at NUTRITION 2024, the American Academy of Nutrition's flagship annual meeting, taking place June 29-July 2 in Chicago.
Liu's research team focuses on discovering bioactive compounds from natural products for diabetes management. Previously, they had looked for specific molecular targets for natural compounds in parts of the body that help actively regulate metabolism, such as the pancreas, muscle, adipose tissue and liver. However, natural products usually have low bioavailability, so they decided to instead explore whether they could indirectly regulate metabolic function by targeting metabolic hormone secretion in the gut.
In this new study, the researchers began by identifying natural compounds that act on L-cells containing two metabolic hormones secreted during eating. Called GLP-1 and PYY, these hormones work together to promote satiety and prevent overeating, as well as control blood sugar levels and metabolism. The screening process revealed that elenolic acid, found in mature olives and extra virgin olive oil, can trigger the secretion of these hormones in the intestine. The researchers were able to produce elenolic acid by breaking down its precursor, oleuropein, which is cheaper than extracting it directly from olives.
Testing the compound in obese mice with diabetes revealed that mice given oral elenolic acid had significantly improved metabolic health compared to obese control mice: after 4-5 weeks of treatment, the mice's obesity was reduced by 10.7%, and their blood glucose levels and insulin sensitivity were comparable to those of healthy lean mice.
Elenolic acid significantly reduced food intake and promoted weight loss, which was associated with increased circulating levels of PYY and GLP-1 and downregulation of hypothalamic agouti-related peptide, which is known to increase food intake and weight gain when overexpressed.
“Overall, our study revealed that olive elenolic acid has promising effects on hormone secretion and metabolic health, especially in obesity and diabetes conditions,” Liu said. “The compound appears to directly promote metabolic hormone secretion in the gut by mimicking the physiological conditions of a diet, which may help regulate energy balance and metabolic health.”
According to the researchers, the concentrations of elenolic acid in olive oil and olives are very low, so the benefits seen in this study are unlikely to come from olive products alone.
The research team is currently working to analyze how the compound is absorbed, distributed, metabolized, and excreted in the body to understand its metabolic effects, which may also provide safety insights for future clinical trials.
Alkhalidy will present the research at the “Bioactive Compounds in Health and Disease” oral presentation at McCormick Place on Saturday, June 29, from 3:12 to 3:25 p.m. CDT.Abstract; Presentation details).