Researchers from the University of Granada and the Institut d’Investigació Sanitària Pere Virgili (Tarragona) have identified that the levels of a small molecule, succinate, found in plasma could help identify those young people at high risk of cardiovascular disease
The study offers fresh insights in the field of cardiovascular risk biomarkers among the young, and could be key for the development of new therapies to combat obesity and diabetes
A study conducted by researchers from the University of Granada (UGR), in collaboration with researchers from the Institut d’Investigació Sanitària Pere Virgili (IISPV), Tarragona, has identified that the level of circulating succinate-a small molecule identifiable in plasma-could be used for the early identification of individuals with a higher risk of developing cardiovascular disease. The work has been published in the journal Cardiovascular Diabetology, whichspecialises in the study of diabetes and cardiovascular disorders.
Cardiovascular disease is the leading cause of death in the world. Globally, it is estimated that each year about 18 million die people as a result of cardiovascular diseases. In Spain alone, about 120,000 deaths are attributed to it annually. One of the most alarming statistics is that the incidence of cardiovascular disease is increasing among the youngest sectors of the population. Hence, there is an imperative need to implement new tools to identify those individuals with a higher risk of developing this disease in the future.
Succinate is traditionally known for its role as an energy-producing molecule in the Krebs cycle (via the metabolic pathway-that is, a series of chemical reactions that are part of the cellular respiration of all cells that use oxygen). However, it has recently been shown that succinate is also a key molecule in the regulation of the metabolism that plays a role in signalling and communication processes outside the cell, similar to that of hormones and other cytokines.
In a previous study led by Dr. Sonia Fernández-Veledo-head of the IISPV’s DIAMET Research Group on Diabetes and Metabolic Diseases and of the ‘CIBER of Diabetes and Associated Metabolic Diseases’ (CIBERDEM)-it was observed that the circulating succinate levels were elevated in individuals with cardiometabolic and inflammatory diseases, such as obesity and type-2 diabetes.
This group also demonstrated that succinate levels were linked to a greater abundance of bacteria in the gut microbiota that produce this molecule as a product of their metabolism. Other studies have found that succinate activates brown adipose tissue, a type of fat that is associated with better cardiovascular health. For all these reasons, the involvement of succinate in metabolism and its relationship with health and disease have resulted in an exponential increase in scholarly interest in this molecule.
Cardiovascular risk in young adults
In the study led by the UGR, circulating succinate levels in plasma were measured in a total of 100 young people aged 18-25 years. Their body composition, nutritional intake patterns, brown adipose tissue volume, and general activity levels were analysed, along with the composition of their intestinal microbiota. In addition, their levels of circulating oxylipins (molecules derived from omega-3 and omega-6 fatty acids) were measured, as these play a very important role in anti- and pro-inflammatory processes, respectively.
The study detected no link between succinate levels and the individual’s activity level, the volume of brown adipose tissue, or the composition of their gut microbiota. However, succinate levels were positively associated with cardiometabolic risk-markers such as increased visceral adipose tissue, diastolic blood pressure, levels of triglyceride and levels of C-reactive protein-an important inflammatory marker.
Individuals presenting higher levels of succinate also had higher levels of omega-6 oxylipins in the blood, which are associated with the pathophysiology of obesity and poorer cardiovascular health.
Clinical implications of the study
The study shows that succinate is a biomarker linked to cardiovascular risk factors in young adults. At the clinical level, measuring succinate levels could serve as a tool for early identification of young individuals who carry a higher risk of developing cardiovascular disease in the future.
The researchers note that additional studies are needed to confirm that circulating succinate levels truly reflect the cardiovascular status of individuals, and to validate its usefulness as a potential marker of cardiovascular risk among young-adult populations. The study of succinate therefore constitutes a promising line of research for the development of new treatments in the fight against obesity, diabetes, and cardiovascular disease.
Osuna-Prieto FJ, Martinez-Tellez B, Ortiz-Alvarez L, Di X, Jurado-Fasoli L, Xu H, Ceperuelo-Mallafré V, Núñez-Roa C, Kohler I, Segura-Carretero A, García-Lario JV, Gil A, Aguilera CM, Llamas-Elvira JM, Rensen PCN, Vendrell J, Ruiz JR, and Fernández-Veledo S. (2021), ‘Elevated plasma succinate levels are linked to higher cardiovascular disease risk factors in young adults’, Cardiovasc Diabetol. 20(1):151.
doi: 10.1186/s12933-021-01333-3. PMID: 34315463; PMCID: PMC8314524.
Metabolic interactions of succinate with peripheral tissues and organs. Succinate can be produced in the mitochondria or by bacteria in the gut microbiota. When it reaches the blood, succinate exerts its endocrine actions in very diverse peripheral tissues and organs, such as the pancreas, adipose tissue, kidneys, muscle, or the immune system.
UGR researchers Borja Martínez and Francisco Javier Osuna