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Lipid Metabolism and Biomarkers in Neural and Cardiometabolic Health

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A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Endocrinology and Metabolism".

Deadline for manuscript submissions: closed (20 December 2025) | Viewed by 12384

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Dr. Elena Vianello

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Department of Biomedical Sciences for Health, Università degli Studi di Milano, Milan, Italy
Interests: inflammation; inflammatory disorders; biomarkers; molecular mechanism of inflammation; molecular signaling
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Lipid species are a part of bioorganic compounds that play a crucial role in heart and neural health.

Due to their role in maintaining physiological activities like organ energy balance, membrane integrity, enzyme functions, nerve pulse transmission, or muscle contraction, different studies are now focused on the bioactive lipid compound characterization and profiling in health and disease states. Lipid dysregulation has emerged as a common feature of major cardiac and neural degenerative diseases.

Often, lipid deregulation can promote mechanical stress on the heart resulting in arterial hypertension and hypertrophic molecular signalling associated with the release of cytokines and chemokines involved in compensatory mechanisms leading to heart remodelling. Furthermore, some cytokines and chemokines associated with cardiac disorders are closely related to neural health and stability. The Special Issue aims to reveal the molecular mechanisms associated with the deregulation of bioactive lipids and cytokines and chemokines release in normal and pathological conditions associated with cardiac and neural stability. The study of novel interaction of lipids on heart and neural pathophysiology may become a good basis for potential treatments or prevention strategies in cardiac and neural health.

Dr. Elena Vianello
Guest Editor

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Keywords

lipid species
cardiovascular health
neural health
inflammation
cardiac biomarkers
neural biomarkers

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Published Papers (6 papers)

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Research

Jump to: Review, Other

23 pages, 468 KB

Open AccessArticle

Correlation of Lp(a), ApoB and oxLDL with Endothelial Damage Reading in Patients with Different Degrees of Coronary Atherosclerosis

by Agnė Liuizė (Abramavičiūtė), Jolanta Laukaitienė, Renata Paukštaitienė, Viltė Marija Gintauskienė and Aušra Mongirdienė

Int. J. Mol. Sci. 2026, 27(3), 1160; https://doi.org/10.3390/ijms27031160 - 23 Jan 2026

Viewed by 772

Abstract

This pilot hypothesis-generating study evaluated whether lipid-related biomarkers (Lp(a), ApoB, and oxLDL), endothelial injury markers (endocan, vimentin), and extracellular matrix glycoproteins (TSP-1, TSP-2) reflect the severity of coronary artery disease (CAD) in patients with stable angina pectoris. 93 patients underwent invasive coronary angiography/coronary CT angiography. CAD severity was evaluated using Gensini, SIS, SSS, and CAD-RADS scores. CAD was confirmed in 76.3% (n = 71). OxLDL correlated with Gensini (r = 0.455; p = 0.006), atherosclerotic segments (r = 0.469; p = 0.005), arteries (r = 0.479; p = 0.004), revascularization indication (r = 0.318; p = 0.003), circumflex artery stenosis (r = 0.323; p = 0.005). OxLDL also correlated with vimentin (r = 0.459; p < 0.001). Vimentin correlated with Gensini (r = 0.480; p = 0.005), SIS (r = 0.349; p = 0.003), SSS (r = 0.320; p = 0.008), CAD-RADS (r = 0.331; p = 0.005), atherosclerotic segments (r = 0.515; p = 0.003), arteries (r = 0.384; p = 0.030), revascularization indication (r = 0.324; p = 0.003). Endocan, TSP-1, and TSP-2 showed no significant associations. These exploratory findings suggest that oxLDL and vimentin may be associated with CAD severity; however, confirmation in larger, prospective cohorts is required. Full article

(This article belongs to the Special Issue Lipid Metabolism and Biomarkers in Neural and Cardiometabolic Health)

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18 pages, 1817 KB

Open AccessArticle

Hypoxic Training with Calorie Restriction Improves Lipid Profile and Body Composition in Men with Obesity-Related Hypercholesterolemia: A Controlled Intervention Study

by Emil Jędrzejewski, Miłosz Czuba, Adam Niemaszyk, Kamila Płoszczyca, Katarzyna Kaczmarczyk, Józef Langfort and Robert Gajda

Int. J. Mol. Sci. 2025, 26(22), 11048; https://doi.org/10.3390/ijms262211048 - 14 Nov 2025

Viewed by 1737

Abstract

Obesity and overweight conditions, frequently accompanied by hypercholesterolemia, are major risk factors for cardiovascular disease. Lifestyle interventions remain the cornerstone of non-pharmacological treatment; however, their effectiveness in improving lipid profiles is limited. Intermittent hypoxic training (IHT) has recently emerged as a potential strategy to enhance metabolic outcomes. This study aimed to evaluate the effects of a 4-week intensive IHT program combined with a calorie-restricted diet on lipid profile and body composition in men with overweight or obesity and secondary hypercholesterolemia. Twenty physically inactive men (35.3 ± 5.4 years) were randomly assigned to either a hypoxic group (H, n = 10) or a normoxic control group (C, n = 10). Both groups followed the same training protocol and diet, differing only in environmental training conditions. Body composition, resting metabolic rate, and blood lipid parameters (total cholesterol, TC; high-density lipoprotein cholesterol, HDL-C; low-density lipoprotein cholesterol, LDL-C; non-high-density lipoprotein cholesterol, non-HDL-C; Triglycerides, TG) were assessed before and after the intervention. Compared with the C group, participants in the H group achieved significantly greater reductions in body mass (−5.4% vs. −2.6%, p < 0.05) and fat mass (−14.7% vs. −7%, p < 0.01). IHT also induced marked decreases in TC (−22.6%, p < 0.001), LDL-C (−25.8%, p < 0.001), non-HDL-C (−26.5%, p < 0.001), and TG (−31.4%, p < 0.01), along with a significant improvement in the atherogenic index of plasma (AIP, −24.4%, p < 0.05). In contrast, the C group showed only non-significant downward trends. No significant changes in HDL-C were observed in either group. These findings suggest that IHT combined with dietary restriction produces more favorable changes in lipid profile and body composition than normoxic training. IHT may therefore represent a promising adjunct to conventional lifestyle-based interventions in the management of obesity-related hypercholesterolemia. Full article

(This article belongs to the Special Issue Lipid Metabolism and Biomarkers in Neural and Cardiometabolic Health)

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21 pages, 4842 KB

Open AccessArticle

St. John’s Wort Extract Ze 117 and Escitalopram Alter Plasma and Hippocampal Lipidome in a Rat Model of Chronic-Stress-Induced Depression

by Hendrik Bussmann, Swen Bremer, Anne Marie Hernier, Jürgen Drewe, Hanns Häberlein, Sebastian Franken, Virginie Freytag, Georg Boonen and Veronika Butterweck

Int. J. Mol. Sci. 2024, 25(23), 12667; https://doi.org/10.3390/ijms252312667 - 26 Nov 2024

Cited by 4 | Viewed by 2865

Abstract

Chronic stress is a key factor in the development of depression. It leads to hyperactivation of the hypothalamic–pituitary–adrenal (HPA) axis, which in turn increases the formation of glucocorticoids (GCs). Chronically elevated GC levels disrupt neuroplasticity and affect brain lipid metabolism, which may, ultimately, contribute to the development of depression. This study aimed to investigate the effects of the antidepressants St. John’s Wort extract and escitalopram on lipid metabolism in vivo. Therefore, repeated corticosterone injections were used to induce depression-like behavior in rats. Male Sprague–Dawley rats were stressed with corticosterone injections (40 mg/kg, s.c.) over 22 consecutive days and were concomitantly treated with varying doses of the St. John’s wort extract Ze 117 (30, 90 or 180 mg/kg, p.o.) or escitalopram (10 mg/kg, p.o.) and behavioral changes were evaluated using a modified forced swim test. The results indicate that repeated corticosterone injections significantly decreased the latency to first immobility. Furthermore, co-treatment of corticosterone with Ze 117 increased latency to first immobility significantly compared to rats treated with corticosterone alone. To further investigate the biochemical effects of corticosterone-induced stress, as well as the possible counter-regulation by antidepressants, the lipidomes of the plasma and hippocampus samples were analyzed by shotgun mass spectrometry. Corticosterone-induced stress significantly altered key lipid metabolites in the plasma but not in the hippocampal samples. In the hippocampus, however, specific glycerophospholipids such as lysophosphatidylethanolamines (LPEs) increased with escitalopram treatment and with Ze 117, both showing significant correlations with behavioral parameters. In summary, our study shows significant behavioral- and lipidome-altering processes with Ze 117 and escitalopram in rat plasma and hippocampal samples, thereby providing new targets and biomarker ideas for clinical diagnosis and antidepressant intervention. Full article

(This article belongs to the Special Issue Lipid Metabolism and Biomarkers in Neural and Cardiometabolic Health)

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Review

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23 pages, 1464 KB

Open AccessReview

Biomarkers of Cardiac Metabolic Flexibility in Health, HFrEF and HFpEF

by Hyeong Rok Yun, Manish Kumar Singh, Sunhee Han, Jyotsna S. Ranbhise, Joohun Ha, Sung Soo Kim and Insug Kang

Int. J. Mol. Sci. 2026, 27(2), 879; https://doi.org/10.3390/ijms27020879 - 15 Jan 2026

Cited by 2 | Viewed by 1347

Abstract

Cardiac metabolic flexibility is a key determinant of myocardial energetic resilience. In heart failure with reduced ejection fraction (HFrEF), intrinsic mitochondrial dysfunction and lipotoxicity compromise oxidative capacity. In contrast, heart failure with preserved ejection fraction (HFpEF) is orchestrated primarily by systemic comorbidities and coronary microvascular dysfunction, which decouple glycolysis from glucose oxidation. This review integrates these distinct pathophysiologies into a comprehensive biomarker framework. Beyond core hemodynamic markers, we detail indices of metabolic flux (ketones, acylcarnitines, branched-chain amino acids), endothelial injury, and fibrosis. We further prose a shift from static, isolated measurements to dynamic functional profiling using standardized challenges (e.g., mixed-meal or exercise tests) to quantify metabolic suppression and recovery kinetics. This structured hierarchy enables phenotype-tailored risk stratification and guides mechanism-based precision therapies in the era of personalized medicine. Full article

(This article belongs to the Special Issue Lipid Metabolism and Biomarkers in Neural and Cardiometabolic Health)

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44 pages, 2369 KB

Open AccessReview

Brain–Bone Axis in Physiological and Pathological Conditions

by Luca Massaccesi, Massimiliano Marco Corsi Romanelli and Emanuela Galliera

Int. J. Mol. Sci. 2025, 26(19), 9822; https://doi.org/10.3390/ijms26199822 - 9 Oct 2025

Cited by 6 | Viewed by 3246

Abstract

The brain–bone axis has garnered increasing attention over the years, leading to numerous studies that have unraveled the intricate bidirectional communication between the central nervous system (CNS) and skeletal metabolism. This review explores this profound relationship, examining the complex mechanisms that regulate it, the key players involved, and the clinical implications of its dysfunction in various pathological situations affecting the CNS and skeletal system. Ultimately, it emphasizes the potential of ongoing research to develop diagnostic tools, therapeutic interventions, and preventive strategies aimed at enhancing skeletal and neurological health. Full article

(This article belongs to the Special Issue Lipid Metabolism and Biomarkers in Neural and Cardiometabolic Health)

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Other

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11 pages, 1809 KB

Open AccessBrief Report

Fatty Acid Profile in the Liver of Mice with Early- and Late-Onset Forms of Huntington’s Disease

by Magdalena Gregorczyk, Adriana Mika, Tomasz Śledziński, Marta Tomczyk and Iwona Rybakowska

Int. J. Mol. Sci. 2025, 26(15), 7304; https://doi.org/10.3390/ijms26157304 - 28 Jul 2025

Viewed by 1250

Abstract

Huntington’s disease (HD) is characterized by progressive neurodegeneration, but increasing evidence points to multisystemic involvement, including early hepatic steatosis in pediatric HD. Therefore, it is important to consider systemic alterations, particularly in liver lipid metabolism. In this study, we analyzed fatty acid (FA) profiles in two symptomatic HD mouse models: 2-month-old R6/2 mice representing early-onset HD and 22-month-old Hdh^Q150/Q150 (Hdh) mice representing late-onset HD, along with age-matched wild-type (WT) controls. FA composition in liver tissue was assessed by gas chromatography–mass spectrometry (GC–MS). In R6/2 mice, we observed increased levels of total iso-branched chain, monounsaturated, and n-6 polyunsaturated FAs compared to WT. In contrast, only a few FA species showed reduced concentrations in Hdh mice. Overall, our results indicate that R6/2 mice exhibit more pronounced alterations in hepatic FA profiles than Hdh mice, suggesting that early-onset HD may be associated with more severe peripheral metabolic dysregulation. Full article

(This article belongs to the Special Issue Lipid Metabolism and Biomarkers in Neural and Cardiometabolic Health)

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