Obesity-Induced Metabolic Dysregulation and Cardiovascular Impact

Obesity is characterised by excessive adipose tissue expansion and altered metabolic homeostasis, which collectively precipitate a cascade of deleterious effects on cardiovascular health. Central to this pathology is insulin resistance, driven by ectopic lipid accumulation in non-adipose organs and by adipose tissue dysfunction, which includes dysregulated secretion of adipokines and pro-inflammatory cytokines. These perturbations foster chronic low-grade inflammation, oxidative stress and activation of the renin–angiotensin–aldosterone system, all of which contribute to endothelial dysfunction, vascular remodelling and heightened arterial stiffness. The imbalance between reactive oxygen species production and endogenous antioxidant defences further exacerbates vascular injury and promotes atherosclerotic plaque formation. Simultaneously, increased cardiac workload, altered substrate utilisation and myocardial fibrosis undermine cardiac contractility and predispose to heart failure. Given the global rise in obesity prevalence, elucidating the intricate interplay between metabolic derailment and cardiovascular sequelae is critical for the development of effective preventive and therapeutic strategies.

Research from Nature Portfolio

Analyses of a large prospective cohort have quantified the extent to which blood pressure, serum cholesterol and fasting glucose mediate the impact of general and central adiposity on incident cardiovascular disease. Blood pressure emerged as the predominant mediator, accounting for more than half of the obesity-related risk in both sexes, with combined metabolic mediators explaining up to two-thirds of excess risk. This work underscores the importance of early detection and rigorous management of hypertension and dyslipidaemia in individuals with elevated body mass index or waist circumference. In parallel, investigations into mitochondrial-targeted therapeutics have demonstrated that the peptide SS-31 attenuates oxidative stress and inflammatory signalling in leukocytes from patients with type 2 diabetes, restoring SIRT1 levels and improving endothelial interactions. These findings support the potential of mitochondria-directed antioxidants to mitigate cardiovascular risk in metabolically compromised populations.

Obesity-Induced Metabolic Dysregulation and Cardiovascular Impact publication trend

The graph below shows the total number of articles in obesity-induced metabolic dysregulation and cardiovascular impact across all publications each year (not limited to Nature Index journals).

Technical terms

Adipokine: Bioactive peptide or protein secreted by adipose tissue that modulates insulin sensitivity, inflammation and vascular function.

Insulin resistance: A diminished cellular response to insulin, leading to impaired glucose uptake and compensatory hyperinsulinaemia.

Ectopic lipid accumulation: Deposition of triglycerides within non-adipose tissues, such as liver, muscle or myocardium, disrupting cellular metabolism.

Reactive oxygen species (ROS): Chemically reactive molecules containing oxygen that, in excess, cause oxidative damage to lipids, proteins and DNA.

Endothelial dysfunction: Impaired endothelium-dependent vasodilation and barrier function, often the first sign of vascular disease.

References

1. Cardiovascular responses to experimental weight gain in humans: a feasibility study. Journal of Hypertension (2024).
2. Hemostasis, endothelial stress, inflammation, and the metabolic syndrome. Seminars in Immunopathology (2017).
3. Molecular Mechanisms of Obesity-Linked Cardiac Dysfunction: An Up-Date on Current Knowledge. Cells (2021).
4. The mitochondrial antioxidant SS-31 increases SIRT1 levels and ameliorates inflammation, oxidative stress and leukocyte-endothelium interactions in type 2 diabetes. Scientific Reports (2018).
5. Contribution of obesity and cardiometabolic risk factors in developing cardiovascular disease: a population-based cohort study. Scientific Reports (2022).