Researchers from the University of Granada (UGR) and the Institut d'Investigació Sanitària Pere Virgili (IISPV) in Tarragona have identified that blood levels of a small molecule, succinate, could help identify young individuals at high risk of cardiovascular disease. The study offers novel insights into the field of cardiovascular risk biomarkers in the young population and could be key to the development of new therapies against 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) in Tarragona, has identified that circulating levels of a small molecule identifiable in blood, succinate, could be used to identify early individuals at increased risk of developing cardiovascular disease. The work has been published in the journal Cardiovascular Diabetology, specializing in the study of diabetes and cardiovascular disorders.
Cardiovascular disease is the leading cause of death in the world. Globally, it is estimated that nearly 18 million people die each year as a result of cardiovascular disease. In Spain, around 120,000 deaths are attributed to cardiovascular disease each year. One of the most alarming facts is that the incidence of cardiovascular disease is increasing among the younger sectors of the population. For this reason, there is an urgent need to implement new tools to identify those individuals at greatest risk of developing cardiovascular disease in the future.
Why succinate?
Succinate is traditionally known for its role as an energy-producing molecule in the Krebs cycle (metabolic pathway, i.e. a succession of chemical reactions that are part of cellular respiration in all cells that use oxygen). However, it has recently been shown that succinate is also a key molecule in the regulation of metabolism, participating in signaling and communication processes outside the cell, in a similar way to hormones and other cytokines.
In a previous study led by Dr. Sonia Fernández-Veledo, head of the DIAMET group (diabetes and metabolic diseases research group) of the Institut d'Investigació Sanitària Pere Virgili (IISPV) and of the CIBER of Diabetes and Associated Metabolic Diseases (CIBERDEM).), circulating levels of succianthin were found to be elevated in individuals with cardiometabolic and inflammatory diseases, such as obesity and type 2 diabetes.
This group also showed that succinate levels were associated with a higher abundance of gut microbiota bacteria that produce this molecule as a product of their metabolism. Other research has found that succinate is an activator of brown fat, a type of fat that is associated with improved cardiovascular health. Therefore, the involvement of succinate in metabolism and its relationship to health and disease has resulted in an exponential increase in interest in this molecule.
Cardiovascular risk in young adults
In the study led by the UGR, circulating blood levels of succinate were measured in a total of 100 young individuals aged 18-25 years. Their body composition, nutritional intake patterns, brown adipose tissue volume and activity, as well as the composition of their intestinal microbiota were analyzed. In addition, blood levels of oxylipins, molecules derived from omega-3 and omega-6 fatty acids, which play an important role in anti- and pro-inflammatory processes, respectively, were measured.
The results of the study found no association between succinate levels and brown adipose tissue activity or volume, or with gut microbiota composition. However, succinate levels were positively associated with cardiometabolic risk markers such as increased visceral adipose tissue, diastolic blood pressure, triglyceride levels and C-reactive protein, an important marker of inflammation.
In addition, individuals with higher succinate levels also had higher blood levels of omega-6 oxylipins, which are associated with the pathophysiology of obesity and poorer cardiovascular health.
Clinical implications of the study
The study demonstrates that succinate is a biomarker associated with cardiovascular risk factors in young adults. At the clinical level, measuring succinate levels could serve as a tool for early identification of young individuals at increased risk of developing cardiovascular disease.
The researchers point out that further studies are needed to confirm that circulating levels of succinate truly reflect the cardiovascular status of individuals, and to validate its usefulness as a potential marker of cardiovascular risk in young adult populations. Thus, the study of succinate consolidates as a promising line of research for the development of new treatments against obesity, diabetes and cardiovascular disease.
Bibliographic reference:
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, Fernández-Veledo S. Elevated plasma succinate levels are linked to higher cardiovascular disease risk factors in young adults. Cardiovasc Diabetol. 2021 Jul 27;20(1):151. doi: 10.1186/s1293333-021-01333-3. PMID: 34315463; PMCID: PMC8314524.
Images attached:
Metabolic interactions of succinate with peripheral tissues and organs. Succinate can be produced in the mitochondria or by bacteria of the intestinal 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.
Contact us:
Jonatan Ruiz Ruiz
Department of Physical and Sports Education of the UGR
E-mail: ruizj@ugr.es
Francisco Javier Osuna Prieto
Department of Analytical Chemistry of the UGR
E-mail: fjosunaprieto@ugr.es
