ECSS Paris 2023: CP-MH30
INTRODUCTION: Polycystic ovary syndrome (PCOS) is an endocrinopathy associated with vascular dysfunction and insulin resistance, resulting in an elevated cardiovascular disease risk. Exogenous ketone supplementation can decrease blood glucose concentration and has been suggested to improve vascular function via improvements in blood flow in individuals predisposed to cardiovascular disease, but has yet to be assessed in females with PCOS. Therefore, we tested the hypothesis that acute ketone monoester (KME) ingestion would improve glucose-stimulated increases in blood flow in healthy lean females with PCOS. METHODS: Ten otherwise healthy females with PCOS (age: 27 ± 5 yr, body mass index: 23.8 ± 2.7 kg/m2, physical activity: 229 ± 111 min/week), participated in a randomized, double-blind, placebo controlled, acute crossover intervention study. In the overnight post-absorptive state, participants consumed the KME (R)-3-hydroxybutyl (R)-3-hydroxybutyrate (0.45 ml/kg body mass) or a taste-matched non-caloric placebo 30 minutes prior to completing a 2-hour 75g oral glucose tolerance test (OGTT). Venous blood samples to assess beta-hydroxybutyrate (β-OHB) concentrations were collected at baseline, at 30-min after KME intake and concurrent with OGTT ingestion (time point 0), and at 15, 30, 60, 90, and 120-min post-OGTT. Blood pressure (measured via finger photoplethysmography calibrated to manual sphygmomanometry) was continuously recorded throughout the OGTT. Leg blood flow (LBF; duplex ultrasound, superficial femoral artery) and femoral vascular conductance (FVC; LBF/mean arterial pressure) were assessed at baseline and at 0, 15, 30, 60, 90, 120-min post-OGTT. RESULTS: In the placebo trial, blood β-OHB concentration, LBF, and FVC remained unchanged throughout the OGTT (main effects of time all P>0.05). In contrast, KME intake significantly elevated blood β-OHB concentration, reaching 3.1 ± 0.8 mM within 30 minutes and remained elevated throughout the OGTT (main effect of time P<0.01). Additionally, KME ingestion led to a sustained increase in both LBF and FVC across all OGTT timepoints (main effects of time all P<0.01). Notably, peak OGTT-induced increases in LBF (+171 ± 50 vs. +27 ± 14 mL/min, P<0.01) and FVC (+1.9 ± 0.7 vs. +0.5 ± 0.3 mL/min/mmHg, P<0.01) were greater in the KME compared to placebo trial. CONCLUSION: These findings suggest that acute KME ingestion enhances glucose-stimulated vascular function in lean females with PCOS. Notably, this lean, physically active phenotype of PCOS is frequently overlooked in both research and clinical interventions, despite evidence suggesting it may represent the most severe form of the disorder. Given the heightened cardiovascular disease risk in this cohort, KME supplements may offer a potential therapeutic strategy in the managements and prevention of cardiometabolic disease risk in females with PCOS.
Read CV Danielle BerbrierECSS Paris 2023: CP-MH30
INTRODUCTION: Crohns disease (CD) is an inflammatory bowel disease affecting over 2 million people in Europe, significantly impacting patients quality of life. In a preliminary study conducted in our laboratory, an in vitro screening of 17 probiotic strains and 3 plant extracts led to the identification of a promising combination capable of reducing the adhesion of Adherent-Invasive Escherichia coli (AIEC), a pathobiont bacteria involved in CD, to intestinal epithelial cells and mitigating inflammation. Building on these findings, the present study aimed to evaluate, in a mouse model of CD, the potential of a formulation combining two Lacticaseibacillus strains and walnut leaf extract, together with the protective effects of spontaneous physical activity (PA), known to reduce systemic and tissue inflammation. METHODS: Male C57BL/6 mice were initially assigned to either a normal diet (control) or a high-fat diet (HFD) for 11 weeks to induce obesity. Following this period, HFD-fed mice were further divided into four subgroups: two groups had access to spontaneous PA (individually housed with running wheels) for an additional 11 weeks while the other two groups remained sedentary (with locked wheels), each condition receiving either the formulation or not. Mice received oral gavage of the formulation or placebo once daily, 5 days a week, for 5 weeks from the 7th week of PA. During the final two weeks before sacrifice, colitis was induced by adding 1% DSS to the drinking water, with or without an additional challenge with AIEC bacteria to mimic CD, resulting in the formation of eight distinct subgroups. RESULTS: After the first 11 weeks, HFD-fed mice exhibited significantly higher body mass gain (p < 0.0001) than control. During the second phase, despite consuming significantly more energy (p < 0.0001), physically active mice gained less mass than their sedentary counterparts (p = 0.0027). A negative correlation (r = -0.4704, p = 0.01) was observed between total distance covered and weight gain. The combination of probiotics and plant extracts had no significant effect on body mass or PA levels. Neither PA, the formulation, nor their combination had a significant effect on post-mortem muscle mass (soleus, gastrocnemius, or tibialis anterior) or adipose tissue mass (epididymal or mesenteric). On the day of sacrifice, the Disease Activity Index score, measuring colitis severity, and fecal lipocalin-2 levels, an indicator of intestinal inflammation, remained unaffected across conditions. CONCLUSION: The formulation, spontaneous PA, or their combination failed to show effectiveness in the primary prevention of acute intestinal inflammation induced by DSS or DSS + AIEC. Further analyses of serum and tissue inflammation, dysbiosis markers, intestinal permeability, and microbiota composition will complement these data for a better understanding of these findings.
Read CV Fanny De ClercqECSS Paris 2023: CP-MH30
INTRODUCTION: Hyaluronan (HA) is a non-sulfated glycosaminoglycan widely utilized in medical and pharmaceutical applications, particularly in muscle tissue repair. Recent studies highlight its crucial role in muscle regeneration, demonstrating that HA activates muscle stem cells by promoting JMJD3-driven hyaluronic acid synthesis, facilitating adaptation to inflammation and initiating the repair process (1). METHODS: In this study, we investigated the potential of HA in rescuing myoblasts exposed to oxidative and inflammatory stress using C2C12 murine muscle cells. We first performed a wound healing assay to assess cell monolayer repair at baseline (t0) and after 24 hours (t1), in the presence or absence of an HA blend (2–1000 KDa, 1 mg/ml, Regenflex T&M, Regenyal Laboratories SRL), with or without pro-inflammatory agents (IL-1β, TNF-α, LPS) and oxidative stressors (H2O2), known to impair proliferation. RESULTS: Results revealed that HA significantly improved reparative mechanisms even in the presence of inflammatory and oxidative stimuli. Additionally, we evaluated the myogenic potential of C2C12 cells treated with HA by analyzing the expression of key myogenic markers, including MyoD, Mrf4, myogenin, and IGF-1, under the same stress conditions. Preliminary findings indicate that HA exerts a strong pro-proliferative effect, enhancing wound healing within 24 hours post-injury. Moreover, HA treatment upregulated myogenic biomarkers, suggesting a positive impact on differentiation pathways. CONCLUSION: These results support the potential use of this HA formulation as a promising therapeutic strategy for muscle tissue regeneration
Read CV Fabio FerriniECSS Paris 2023: CP-MH30