DIABETES: The revolutionary discovery of therapeutic lipids

Therefore, the prevalence of diabetes is increasing along with that of obesity, resulting in 1.5 million deaths worldwide every year, according to the World Health Organization (WHO). Type 1 diabetes is a chronic condition in which the insulin-producing cells in the pancreas are damaged and stop producing insulin. Therefore, the disease develops when the body becomes resistant or desensitized to insulin.

These 2 forms of the disease lead to high blood sugar levels which, over time, can cause serious damage to the heart, blood vessels, eyes, kidneys and nerves if not properly controlled by a doctor. Although there are now several classes of drugs and many types of devices used to self-monitor blood glucose, many patients have difficulty maintaining this control and the risk of complications remains high.

This key enzyme could be crucial for millions of diabetics

BIDMC endocrinologists have indeed identified a key enzyme in the synthesis of a new class of lipids called FAHFAs (Fatty Acid (FA) Esters of Hydroxy-Fas), which are produced in human tissue and which have positive effects on insulin sensitivity, glycemic control and other metabolic parameters in humans and mice.

The prospect of a brand new treatment for diabetes Type 2, but also type 1: The principle would be to safely replace insulin-producing beta cells in the pancreas in people with type 1 diabetes and to protect these cells from attacks by the immune system, explains first author Dr. Barbara B. Kahn, Vice President of Medical Research at BIDMC: “We show that these FAHFA lipids protect beta cells from immune attack and metabolic stress. By increasing FAHFA levels, we can reduce the severity of type 1 and type 2 diabetes

a real scientific breakthrough,

because it allows us to understand how these lipids are made in mammalian tissues.”

Lipids called FAHFA: Back in 2014, the same team discovered this class of lipids called FAHFA (or hydroxy fatty acid esters). The new study confirms:

  • FAHFA levels are related to insulin sensitivity;
  • Also in obese and diabetic mice, FAHFAs improve glycemic control, reverse type 2 diabetes and reduce pro-inflammatory immune responses;
  • these lipids also protect the human insulin-producing cells, pancreatic islet beta cells, from attack by immune cells and cellular stress;
  • Finally, serum and adipose tissue levels of these lipids are low in people at risk for, or who have, type 2 diabetes.

The ATGL enzyme (adipose triglyceride lipase), plays a key role in the synthesis of these FAHFA lipids. Experiments performed on mice and human and mouse cells indicate that ATGL is the major biosynthetic enzyme of FAHFA in adipose tissue. Further research is needed to determine whether ATGL is also the main biosynthetic enzyme in other tissues and whether other enzymes are involved in the synthesis of these beneficial lipids.

It is clear that these new data open the way to new therapeutic strategies against diabetes, targeting the ATGL enzyme or directly targeting the FAHFAs. Since people who are both obese and insulin-resistant have lower levels of ATGL in white adipose tissue than lean people or people who are obese but insulin-sensitive, scientists suspect that ATGL downregulates FAHFA levels.

Finally, this discovery could also contribute to a new prophylaxis: increasing FAHFA levels in people at risk for type 1 diabetes to prevent the disease.

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