Prediabetes is a condition affecting more than 35% of the population. In some forms, excessive carbohydrate intake (primarily refined sugar) plays a prominent role. Prediabetes is a symptomless, mostly unrecognized disease which increases cardiovascular risk. In our work, we examined the effect of a fructose-enriched diet on cardiac function and lipidome as well as proteome of cardiac muscle. Male Wistar rats were divided into two groups. The control group received a normal diet while the fructose-fed group received 60% fructose-supplemented chow for 24 weeks. Fasting blood glucose measurement and oral glucose tolerance test (OGTT) showed slightly but significantly elevated values due to fructose feeding indicating development of a prediabetic condition. Both echocardiography and isolated working heart perfusion performed at the end of the feeding protocol demonstrated diastolic cardiac dysfunction in the fructose-fed group. Mass spectrometry-based, high-performance lipidomic and proteomic analyses were executed from cardiac tissue. The lipidomic analysis revealed complex rearrangement of the whole lipidome with special emphasis on defects in cardiolipin remodeling. The proteomic analysis showed significant changes in 75 cardiac proteins due to fructose feeding including mitochondria-, apoptosis-, and oxidative stress-related proteins. Nevertheless, just very weak or no signs of apoptosis induction and oxidative stress were detected in the hearts of fructose-fed rats. Our results suggest that fructose feeding induces marked alterations in the cardiac lipidome, especially in cardiolipin remodeling, which leads to mitochondrial dysfunction and impaired cardiac function. However, at the same time, several adaptive responses are induced at the proteome level in order to maintain a homeostatic balance. These findings demonstrate that even very early stages of prediabetes can impair cardiac function and can result in significant changes in the lipidome and proteome of the heart prior to the development of excessive oxidative stress and cell damage.

BackgroundThere is a spectacular rise in the global prevalence of type 2 diabetes mellitus (T2DM) due to the worldwide obesity epidemic. However, a significant proportion of T2DM patients are non-obese and they also have an increased risk of cardiovascular diseases. As the Goto-Kakizaki (GK) rat is a well-known model of non-obese T2DM, the goal of this study was to investigate the effect of non-obese T2DM on cardiac alterations of the transcriptome in GK rats.MethodsFasting blood glucose, serum insulin and cholesterol levels were measured at 7, 11, and 15 weeks of age in male GK and control rats. Oral glucose tolerance test and pancreatic insulin level measurements were performed at 11 weeks of age. At week 15, total RNA was isolated from the myocardium and assayed by rat oligonucleotide microarray for 41,012 genes, and then expression of selected genes was confirmed by qRT-PCR. Gene ontology and protein–protein network analyses were performed to demonstrate potentially characteristic gene alterations and key genes in non-obese T2DM.ResultsFasting blood glucose, serum insulin and cholesterol levels were significantly increased, glucose tolerance and insulin sensitivity were significantly impaired in GK rats as compared to controls. In hearts of GK rats, 204 genes showed significant up-regulation and 303 genes showed down-regulation as compared to controls according to microarray analysis. Genes with significantly altered expression in the heart due to non-obese T2DM includes functional clusters of metabolism (e.g. Cyp2e1, Akr1b10), signal transduction (e.g. Dpp4, Stat3), receptors and ion channels (e.g. Sln, Chrng), membrane and structural proteins (e.g. Tnni1, Mylk2, Col8a1, Adam33), cell growth and differentiation (e.g. Gpc3, Jund), immune response (e.g. C3, C4a), and others (e.g. Lrp8, Msln, Klkc1, Epn3). Gene ontology analysis revealed several significantly enriched functional inter-relationships between genes influenced by non-obese T2DM. Protein–protein interaction analysis demonstrated that Stat is a potential key gene influenced by non-obese T2DM.ConclusionsNon-obese T2DM alters cardiac gene expression profile. The altered genes may be involved in the development of cardiac pathologies and could be potential therapeutic targets in non-obese T2DM.Electronic supplementary materialThe online version of this article (doi:10.1186/s12933-016-0424-3) contains supplementary material, which is available to authorized users.

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Background and goals: Nowadays sedentary lifestyle and carbohydrate-and lipid-rich diet are huge problems worldwide. These habits can lead to the development of many pathological conditions, primarily obesity and diabetes mellitus (DM). DM is in fact a group of metabolic disorders and the main cause of the pathological changes here is hyperglycemia. This elevated blood glucose level can damage several organs, such as the heart, blood vessels, kidneys and eyes. Since cardiovascular diseases (CVD) are responsible for a significantly high proportion of death cases in the world, our research was focusing on the cardiac effects of DM. Although I.

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