Hypoxia occurs in the splanchnic region during exercise associated with sympathetic activity. In the elderly, vascular insufficiency and low vascular endothelial growth factor (VEGF) expression are observed. Compared to young people, sympathetic signals of older individuals are blunted and more resistant to splanchnic blood flow alterations during exercise. VEGF induces vasodilation responses and hence may retain blood in the splanchnic vascular bed. We hypothesized that regular mild-intensity exercise triggers weak VEGF expression in the digestive tract of the elderly. The effects of exercise on the levels of VEGF, superoxide dismutase (SOD), glutathione peroxidase (GPx), malondialdehyde (MDA) and total antioxidant capacity (T-AOC) in the stomach, jejunum, ileum and colon tissues were evaluated. With exercise, the VEGF levels in the stomach and colon increased. Although the SOD, GPx, and MDA levels decreased in the stomach, they increased in the colon. T-AOC increased in the stomach and there was no change in the jejunum, ileum and colon. The hypoperfusion during exercise was not equal in all regions of the gastrointestinal tract in the aged subjects. Hypoxia and other exercise-related mechanisms could have led to this VEGF induction. The stomach, jejunum, and ileum might have developed resistance to ischemia. The induction of VEGF may be beneficial in aging-associated impaired gastrointestinal homeostasis and neovascularization.

Background/Objectives: Metabolic dysfunction-associated steatotic liver disease (MASLD) is becoming more common among adolescents, but non-invasive biomarkers for early detection are still limited. Liver-expressed antimicrobial peptide-2 (LEAP-2), a ghrelin receptor antagonist, has been connected to obesity and liver fat buildup in adults, but pediatric data are limited. This study investigates the hypothesis that higher levels of LEAP-2 are associated with hepatic steatosis and the role of LEAP-2 serum levels in the earlier and easier diagnosis of MASLD in children. Methods: In this cross-sectional study, 51 adolescents aged 12–18 were divided into three groups: one with MASLD and obesity (MASLD-Ob) (confirmed hepatosteatosis by imaging studies such as magnetic resonance or ultrasound, along with at least one cardiometabolic criterion and a body mass index (BMI) > 2 SD) (n = 19), another with obesity without any liver pathology or MASLD (BMI > 2 SD) (n = 14), and healthy controls (n = 18). The controlled attenuation parameter (CAP) was measured using FibroScan^® Mini + 430 (Echosens SA, Créteil, France), and serum ghrelin and LEAP-2 levels were determined via ELISA. Correlations between LEAP-2, ghrelin, CAP, BMI z-score, and metabolic parameters were analyzed. Results: LEAP-2 and ghrelin levels among the three groups were similar (p = 0.148, p = 0.515). A positive correlation was observed between LEAP-2 levels and CAP values in the obese group (both the MASLD-Ob and obesity groups) (r = 0.379, p = 0.030). When a cutoff of 240 dB/m was used, the median LEAP-2 level in cases above this value was 2.20 ng/mL, compared to 1.37 ng/mL in cases below it (p = 0.021), which was significantly different. When analyzing the obese group (both the MASLD-Ob and obese groups) a statistically significant correlation was found between serum LEAP-2 levels and CAP, AST, GGT, and total bilirubin values (r = 0.379, p = 0.030; r = 0.369, p = 0.035; r = 0.369, p = 0.035; r = 0.357, p = 0.049, respectively). Conclusions: Interventional imaging methods and biomarkers for diagnosing and monitoring hepatosteatosis have become well-established in the literature. However, since these tests are not available at all centers and can be costly, there is an increasing search for other easily accessible diagnostic and follow-up parameters. LEAP-2 could be a promising non-invasive biomarker for pediatric MASLD, especially when used alongside CAP measurements. The application of this biomarker in pediatric MASLD provides valuable data to help identify and monitor the condition in adolescents. We believe our study offers strong evidence to support further research and the development of drug treatments for MASLD that aim to reduce plasma LEAP-2.