Diabetes: what is the relationship between obesity and blood fats with the generation of diseases

Researchers from the University of Leeds, together with colleagues from other academic centres such as Cambridge, Bonn, Bari, Imperial College and specialists from AstraZeneca, were able to detect that patients with metabolic diseases have high levels of fats in the blood. A situation causes stress on muscle cells and causes damage to their structure and performance.

They also detected that these stressed cells emit a signal that can be transmitted to other cells. Alerts, often called ceramides, can have a short-term protective benefit because they are part of a mechanism designed to reduce stress within the cell. But in metabolic diseases, which are long-term conditions, alerts can kill cells, make symptoms more severe, and worsen the disease. This information was published in the specialized journal Nature Communications.

According to the data expressed by the research, the endoplasmic reticulum (ER) is a cellular organelle with a key role both in protein synthesis and folding, and in lipid biosynthesis. Disruption of its function causes stress and protein accumulation. Its uncontrolled accumulation can lead to cell death.

ER stress has been linked to a wide range of conditions, including aging, certain cancers, and metabolic diseases, such as dyslipidemia (an excessive increase in cholesterol and/or triglycerides), obesity, and type 2 diabetes. Metabolic diseases, including the latter two, are characterized by high plasma concentrations of saturated fatty acids, in particular palmitate. These lipid species are thought to induce metabolic dysfunction in insulin-sensitive tissues, such as liver, adipose tissue, and skeletal muscle, through effects called lipotoxicity.

In the past, other research has already confirmed that elevated levels of fat in the blood damage tissues and organs, contributing to the development of cardiovascular and metabolic diseases, including type 2 diabetes. The situation may be due to obesity, whose rates have almost tripled worldwide since 1975, according to data from the World Health Organization (WHO).

In 2016, there were more than 650 million adults over 18 years of age who were obese. Lee Roberts, Professor of Molecular Physiology and Metabolism at the Faculty of Medicine, Leeds Faculty and one of the authors of the latest study said: “Although this research is at an early stage, our discovery could underpin the premise of recent therapies or therapeutic approaches to prevent the event of cardiovascular disease and metabolic diseases such as diabetes in people with high levels of fat in the blood with weight problems”.

For the development of its research, the team reproduced in the laboratory the levels of fat in the blood seen in people with metabolic diseases by exposing skeletal muscle cells to a fatty acid known as palmitate. When that happened, the cells started transmitting the ceramide signal. At the time when these cells combined with others that had not been previously exposed to fat, the researchers discovered that they were communicating with each other, carrying the signal in packages called extracellular vesicles. The experiment was reproduced in human volunteers with metabolic diseases and gave similar results.

The findings show a very special focus on how cells respond to stress, with important consequences for our understanding of certain metabolic diseases, such as obesity. “This analysis gives us a novel perspective on how stress develops within the cells of people with weight problems and provides new avenues to contemplate when trying to develop new remedies for metabolic diseases,” Roberts completed.

He concluded: “With obesity as a growing epidemic, the burden of stress-related diseases, such as type 2 diabetes, requires new treatments. We hope that the results of our research will open up a new avenue of research to help address this growing concern.”

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