Journal Article

Impaired nitric oxide‐dependent endothelial function in young male individuals with obesity before the onset of symptoms and complications

Baldassarre, Giovanni, Caroli, Diana, Suraj‐Prazmowska, Joanna, Chlopicki, Stefan, Sartorio, Alessandro, Majerczak, Joanna, De Micheli, Roberta, Favaretto, Thomas, Grassi, Bruno, Zuccarelli, Lucrezia, Bondesan, Adele, Kurpinska, Anna, Tringali, Gabriella, Zoladz, Jerzy A.

2025

Overview

Endothelial dysfunction drives obesity‐related complications. Doppler ultrasound measurement of blood flow during 1‐min passive leg movements (PLM) is a valuable non‐invasive tool for assessing endothelial function and nitric oxide (NO)‐mediated vasodilation. The objectives of this work were t o identify endothelial dysfunction biomarkers in young individuals with obesity (OB) using the PLM test; to evaluate the effects of a rehabilitation programme on these biomarkers; and to explore associations between PLM data, oxidative metabolism and blood biomarkers of microvascular impairment. Fifteen male OB (age 17 ± 4 years; body mass 121.4 ± 24.1 kg; body mass index 39.3 ± 7.5 kg m −2 ) were tested before (PRE) and after (POST) a 3‐week multidisciplinary body mass reduction programme. Fifteen age‐matched normal‐weight males (CTRL) underwent PRE measurements. Participants performed an incremental exercise, a PLM test and underwent blood biomarker analysis. Peak oxygen uptake and ventilatory thresholds (mL kg −1  min −1 ) were ∼40% lower in OB versus CTRL ( P  < 0.001) and improved by ∼8% in OB POST versus PRE ( P  < 0.05). Plasma nitrite concentration was lower in OB (0.18 ± 0.09 µmol L −1 ) versus CTRL (0.51 ± 0.49; P  = 0.02). Baseline blood flow, normalized for appendicular muscle mass, was similar between the two groups, whereas peak blood flow, Δpeak (difference between peak and baseline) and the area under the blood flow versus time curve were significantly lower in OB PRE, with improvements in OB POST. Several blood biomarkers of endothelial barrier function and permeability differed in OB versus CTRL. The blunted PLM‐induced hyperaemic response and lower plasma nitrite levels indicate impaired endothelial function in young individuals with obesity, occurring before the onset of cardiovascular and metabolic complications. What is the central question of this study? Can passive leg movement (PLM)‐induced hyperaemia and related biomarkers detect early endothelial dysfunction in young individuals with obesity, and are these parameters modifiable by a short‐term rehabilitation programme? What is the main finding and its importance? Young males with obesity exhibit impaired PLM‐induced hyperaemia and reduced plasma nitrite levels, indicating early endothelial dysfunction. A 3‐week multidisciplinary intervention partially improved vascular responses and oxidative metabolism. These findings support the use of PLM as a non‐invasive tool for early detection and monitoring of endothelial dysfunction, before cardiovascular or metabolic complications arise.