Treatment of obesity: study on the protective mechanisms of omega-3 fatty acids

Obesity is a major public health issue today. According to the WHO (World Health Organization), at least 2.8 million people die every year because of their overweight or obesity. The number of obese children and adolescents has increased tenfold in the last 4 years.

Obesity is frequently associated with metabolic disorders, such as insulin resistance, type 2 diabetes, and nonalcoholic liver disease, which are important risk factors for cardiovascular disease.

Supported by the Carrefour Foundation and carried by the Dr. Wilfried Le Goff (INSERM UMR_S1166 – IHU ICAN), the research project entitled “Study of the protective mechanisms of omega-3 fatty acids in obesity” aims to provide a better understanding of the beneficial effects of omega-3 polyunsaturated fatty acids on obesity. It will thus make it possible to propose new therapeutic approaches to combat the development of insulin resistance and type 2 diabetes.

The role of unsaturated fats in preventing obesity

Poor nutrition is an important risk factor in the development of obesity, diabetes and cardiovascular disease. The WHO recommends limiting energy intake from fat consumption by reducing consumption of saturated fats in favor of unsaturated fats.

Although the beneficial role of unsaturated fats in preventing metabolic disorders associated with obesity is widely accepted, the underlying mechanisms are less clear.

These are mainly based on the protective effects associated with omega-3 polyunsaturated fatty acids (PUFAs), particularly against the development of insulin resistance, type 2 diabetes and cardiovascular disease.

From a mechanistic point of view, omega-3 PUFAs would notably reduce inflammation of adipose tissue, the fatty acid storage organ, which is at the origin of the development of insulin resistance and type 2 diabetes during obesity. However, the precise mechanisms are not known.

The study of the protective mechanisms of omega-3 fatty acids

The work of Dr. W. Le Goff’s team (INSERM UMR_S1166 – IHU ICAN) has identified an enzyme that modulates the omega-3 PUFA content of macrophages, the key cells that control inflammation in adipose tissue. Preliminary results indicate that expression of this enzyme mobilizes omega-3 PUFAs from macrophage membranes to reduce inflammation.

This current research project therefore aims to determine whether the beneficial action of omega-3 PUFAs on the development of insulin resistance and type 2 diabetes during obesity requires the anti-inflammatory action of this enzyme in adipose tissue macrophages.

The project will provide a better understanding of the beneficial effects of omega-3 PUFAs in obesity and will allow us to propose new therapeutic approaches to combat the development of insulin resistance and type 2 diabetes.

Within the IHU ICAN, the ICAN Omics platform will perform lipidomic analysis and the ICAN BioCell Flow Cytometry platform will perform cell sorting.

They support this research program

The support of the Carrefour Foundation will contribute to the financing of a researcher’s position on a doctoral contract, the isolation of macrophages from adipose tissue of obese patients by cell sorting and their transcriptomic analysis.

This research program is also funded by the French-speaking Diabetes Society, the Sorbonne University Alliance (Emergence Program) and the French National Research Agency (ANR).

The support of the Crossroads Foundation will be essential for this research program studying the contribution of membrane lipid remodeling in adipose tissue macrophages to the anti-inflammatory role of Omega-3 PUFAs. This work, which will be carried out by a doctoral researcher from our team, will lead to major advances in the understanding of the protective mechanisms of omega-3 PUFAs in obesity.

Wilfried Le Goff – Team leader of Cellular Lipid Metabolism in Cardiovascular Diseases – UMR 1166 / IHU ICAN