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Latest Lipid Discovery Helps Regulate Blood Sugar Levels

Publicado em 02 outubro 2019

Por Agência FAPESP

A team of researchers based in Brazil, the United States, and Germany have discovered a new kind of lipid known as 12-HEPE. 12-HEPE is a liquid produced in response to cold by brown adipose tissue in the human body. The revolutionary new study showed that it helps reduce blood sugar. The results of the team’s experiments with mice carve a way for new treatments for diabetes.

Luiz Osório Leiria, a researcher at the University of Campinas’s Biology Institute (IB-UNICAMP) in São Paulo State, Brazil, led the team. The team also noted that a drug used to treat urinary dysfunction increases the amount of 12-HEPE released into the bloodstream in human patients.

What is adipose tissue?

White adipose tissue is one of the two types of adipose tissues in mammals, including humans. These tissues store excess energy as fat. The other type is called brown adipose tissue. The brown adipose tissue. This tissue converts energy from food into heat and contributes to thermal regulations. This tissue produces several types of lipids in response to cold. One of these lipids is the recently discovered 12-HEPE, whose function was unknown until the team discovered that blood sugar was reduced efficiently in obese mice models treated with 12-HEPE than in untreated mice after they were injected with a concentrated glucose solution.

According to the research paper, the beneficial effects of 12-HEPE on glucose tolerance in obese mice was due to its promotion of glucose uptake into both skeletal muscle and brown adipose tissue. The study conducted on patients showed a possible physiological role for 12-HEPE. The volunteers of the study were divided into three groups, lean, overweight and obese. A detailed analysis of blood samples showed that the lean group had a higher level of 12-HEPE in their blood as compared to the overweight group and much higher than the obese group.

The research was conducted as part of his postdoctoral fellowship at the same university’s School of Medical Sciences (FCM-UNICAMP) during a research internship at Dr. Yu-Hua Tseng Lab at Joslin Diabetes Center, an independent institution affiliated with Harvard Medical School in the US, with support from São Paulo Research Foundation—FAPESP and the American Diabetes Association.

The reason might be that the proportion of brown fat mass is comparatively lower in obese individuals than in lean individuals. Also, the lack of brown fat in obese individuals may account for their obesity and even for the increased risk of diabetes. The discovery lays a new pathway for the development of new drugs to fight diabetes and possible new treatments with already existing drugs.

Proof-of-concept

In the study, another group of healthy lean volunteers received doses of mirabegron. Mirabegron is a drug which is normally prescribed as a medication for treating a urinary syndrome known as overactive bladder, but it can also activate brown adipose tissue. The control group was given only a placebo. The patients who received the drug had an increased plasma level of 12-HEPE. This indicates that the drug could be prescribed as a treatment for diabetes later in the future.

According to the lead author of the study, mirabegron has several effects, some of which are undesirable. It activates the release of various other lipids and does not specifically target glucose reduction. An omega-3 lipid such as 12-HEPE would have a far more toxicological profile. The team is currently conducting tests to estimate the effects of relatively low doses of the drug on blood sugar levels.