A team of endocrinologists from the Beth Israel Deaconess Medical Center (BIDMC) has identified a key enzyme in the synthesis of a new class of lipids (or fats), called lipids FAHFAwhich are produced in human tissues and have beneficial effects on insulin sensitivity, blood glucose and control and other parameters related to metabolism in humans and mice.
About 422 million individuals worldwide are diagnosed with diabetes and 1.5 million deaths are directly attributed to diabetes each year, according to the World Health Organization.. Type 1 diabetes is a chronic condition in which the insulin-producing cells in the pancreas have been damaged and no longer produce insulin; Type 2 diabetes occurs when the body becomes resistant or insensitive to insulin.
Both versions of the disease cause elevated blood glucose levels, or blood sugar, which over time can lead to severe damage to the heart, blood vessels, eyes, kidneys, and nerves if not controlled by treatment. Life-saving drugs and devices have been developed for patients with diabetes, but many people continue to struggle with poor blood sugar control, which puts them at high risk for complications.
The results of the Research conducted by endocrinologists from Beth Israel Deaconess Medical Center (BIDMC) were published in the scientific journal Nature.
FAHFA lipids and diabetes: this is how they work
“The long-term goal is to safely replace the pancreatic beta cells that produce insulin in people with type 1 diabetes, but that would require a way to protect those cells from immune system attacks.“, he has declared Barbara B. Kahnwho is Vice President of Research Strategy at the Department of Medicine of the BIDMC.
“We have shown that these FAHFA lipids protect beta cells from immune attack and metabolic stress. If we could increase FAHFA levels, we think this could be beneficial for both type 1 and type 2 diabetes. Our new discovery is a breakthrough because, for the first time, we know how these lipids are produced in mammalian tissues“, Continued Barbara B. Kahn.
In 2014, the research team coordinated by Kahn in collaboration with Alan SaghatelianProfessor al Salk Institute, discovered the previously unknown class of lipids FAHFA (which stands for fatty acid esters of hydroxyl fatty acids). In humans, FAHFA levels are linked to insulin sensitivity. FAHFA lipids improve blood glucose control in diabetic mice and reduce proinflammatory immune responses, which results in a lower incidence of type 1 diabetes in mice.
FAHFA lipids also protect insulin-producing cells in the human body, known as pancreatic islet beta cells, from attack by immune cells and cellular stress.. Conversely, the levels of these lipids are low in the serum and adipose tissue of individuals at risk or already diagnosed with type 2 diabetes.
In the new research, the team of endocrinologists led by Dr. Kahn in collaboration with Saghatelian found that an enzyme called adipose triglyceride lipase, or ATGL, plays a key role in FAHFA lipid synthesis. The experiments, conducted in mice and human and mouse cells, led by first author Rucha Patel, a BIDMC researcher, and second author, Anna Santoro, an instructor at BIDMC, revealed that ATGL is the main enzyme. biosynthetic for FAHFAs in fat tissues. Further studies will need to investigate whether ATGL is also the main biosynthetic enzyme in other tissues and whether additional enzymes help synthesize beneficial lipids.
The discovery could ultimately pave the way for the development of new therapeutic treatments for people diagnosed with diabetes. Because humans who are both obese and insulin resistant have lower levels of ATGL in white adipose tissue than lean people or people who are both obese and insulin sensitive, the research team speculated that ATGL may contribute to the reduction of FAHFA lipids in insulin resistant people and hence the risk or severity of type 2 diabetes.
“Ideally, the new findings could be used to increase FAHFA levels in people at risk for type 2 diabetes to prevent it, or to improve blood sugar control in people who already have type 2 diabetes.Said Kahn, who is also the Minot Professor of Medicine at Harvard Medical School and member of the National Academy of Sciences.
“Additionally, these new findings could be used to increase FAHFA levels in people at risk for type 1 diabetes to prevent it, as we did in mice. Understanding the regulation of ATGL could lead to disease-mediated strategies to increase these beneficial lipids in metabolism and immune systems.”, Concluded the expert.
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