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Purpose: Preculturing isolated islets with Mesenchymal Stromal Cells (MSCs) improves their functional survival in vitro and subsequent transplantation outcomes in vivo. The MSC secretory product Annexin A1 (ANXA1) is a key modulator of MSC-mediated improvements in islet function. The current study aims to determine the influence of MSCs and defined MSC secretory products, including ANXA1, on the inflammatory crosstalk between isolated islets and Endothelial Cells (ECs), using in vitro models of the clinically-preferred intraportal islet transplantation niche., Methods: Islets were cultured alone, with MSCs, or with MSC secretory products and exposed to pro-inflammatory cytokines. Islet gene expression of C-C Motif Chemokine Ligand 2 (CCL2), C-X-C Motif Chemokine Ligand (CXCL)-10 (CXCL10) and CXCL1 were assessed by RT-qPCR. EC activation was induced with 100 U/ml TNF for 24 h. Islet-EC co-cultures were used to determine the influence of MSCs, or MSC secretory products on the inflammatory crosstalk between isolated islets and ECs. VCAM-1 and ICAM-1 expression were assessed at the mRNA and protein level in ECs, using RT-qPCR and immunofluorescence., Results: MSCs reduce pro-inflammatory cytokine-induced islet CCL2, CXCL10, and CXCL1 gene expression, which is partially mimicked by ANXA1. MSCs and ANXA1 have a similar capacity to reduce TNF-induced EC activation. Isolated islets exacerbate TNF-induced EC activation. Preculturing islets with MSCs reduces islet-exacerbated EC activation. ANXA1 reduces islet-exacerbated EC activation, when present during the islet preculture and islet-EC co-culture period., Conclusion: MSC-derived secretory factors, including ANXA1, may be used in islet transplantation protocols to target donor islet and host EC inflammation at the intraportal niche., (© 2024. The Author(s).)

Context: It is unclear how white adipose tissue (WAT) inflammatory signaling proteins respond during the early stages of overnutrition., Objective: To investigate the effect of short-term, high-fat overfeeding on fasting abdominal subcutaneous WAT total content and phosphorylation of proteins involved in nuclear factor-κB (NF-κB) inflammatory signaling, systemic metabolic and inflammatory biomarkers., Design: Individuals consumed a high-fat (65% total energy from total fat), high-energy (50% above estimated energy requirements) diet for 7 days., Results: Fifteen participants (aged 27 ± 1 years; body mass index 24.4 ± 0.6 kg/m2) completed the study. Body mass increased following high-fat overfeeding (+1.2 ± 0.2 kg; P < 0.0001). However, total content and phosphorylation of proteins involved in NF-κB inflammatory signaling were unchanged following the intervention. Fasting serum glucose (+0.2 ± 0.0 mmol/L), total cholesterol (+0.4 ± 0.1 mmol/L), low-density lipoprotein cholesterol (+0.3 ± 0.1 mmol/L), high-density lipoprotein cholesterol (+0.2 ± 0.0 mmol/L), and lipopolysaccharide-binding protein (LBP; +4.7 ± 2.1 µg/mL) increased, whereas triacylglycerol concentrations (-0.2 ± 0.1 mmol/L) decreased following overfeeding (all P < 0.05). Systemic biomarkers (insulin, soluble cluster of differentiation 14 [CD14], C-reactive protein, interleukin-6, tumor necrosis factor-α and monocyte chemoattractant protein-1) and the proportion and concentration of circulating CD14+ monocytes were unaffected by overfeeding., Conclusion: Acute lipid oversupply did not impact on total content or phosphorylation of proteins involved in WAT NF-κB inflammatory signaling, despite modest weight gain and metabolic alterations. Systemic LBP, which is implicated in the progression of low-grade inflammation during the development of obesity, increased in response to a 7-day high-fat overfeeding period., (© Endocrine Society 2020. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Obese individuals exhibit a diminished muscle protein synthesis response to nutrient stimulation when compared with their lean counterparts. However, the effect of obesity on exercise-stimulated muscle protein synthesis remains unknown. Nine lean (23.5 ± 0.6 kg/m 2 ) and 8 obese (33.6 ± 1.2 kg/m 2 ) physically active young adults participated in a study that determined muscle protein synthesis and intracellular signaling at rest and following an acute bout of resistance exercise. Mixed muscle protein synthesis was determined by combining stable isotope tracer ([ 13 C 6 ]phenylalanine) infusion with serial biopsies of the vastus lateralis. A unilateral leg resistance exercise model was adopted so that resting and postexercise measurements of muscle protein synthesis could be obtained simultaneously. Obesity was associated with higher basal levels of serum insulin (P < 0.05), plasma triacylglycerol (P < 0.01), plasma cholesterol (P < 0.01), and plasma CRP (P < 0.01), as well as increased insulin resistance determined by HOMA-IR (P < 0.05). However, resting and postexercise rates of muscle protein synthesis were not significantly different between lean and obese participants (P = 0.644). Furthermore, resistance exercise stimulated muscle protein synthesis (~50% increase) in both groups (P < 0.001), with no difference between lean and obese (P = 0.809). Temporal increases in the phosphorylation of intracellular signaling proteins (AKT/4EBP1/p70S6K) were observed within the exercised leg (P < 0.05), with no differences between lean and obese. These findings suggest a normal anabolic response to muscle loading in obese young adults., (© 2018 The Authors. Physiological Reports published by Wiley Periodicals, Inc. on behalf of The Physiological Society and the American Physiological Society.)

A diet rich in vegetables is known to provide cardioprotection. However, it is unclear how the consumption of different vegetables might interact to influence vascular health. This study tested the hypothesis that nitrate-rich vegetable consumption would lower systolic blood pressure but that this effect would be abolished when nitrate-rich and thiocyanate-rich vegetables are co-ingested. On four separate occasions, and in a randomized cross-over design, eleven healthy males reported to the laboratory and consumed a 750 mL vegetable smoothie that was either: low in nitrate (∼0.3 mmol) and thiocyanate (∼5 μmol), low in nitrate and high in thiocyanate (∼72 μmol), high in nitrate (∼4 mmol) and low in thiocyanate and high in nitrate and thiocyanate. Blood pressure as well as plasma and salivary [thiocyanate], [nitrate] and [nitrite] were assessed before and 3 h after smoothie consumption. Plasma [nitrate] and [nitrite] and salivary [nitrate] were not different after consuming the two high-nitrate smoothies, but salivary [nitrite] was higher after consuming the high-nitrate low-thiocyanate smoothie (1183 ± 625 μM) compared to the high-nitrate high-thiocyanate smoothie (941 ± 532 μM; P < .001). Systolic blood pressure was only lowered after consuming the high-nitrate low-thiocyanate smoothie (-3 ± 5 mmHg; P < .05). The acute consumption of vegetables high in nitrate and low in thiocyanate lowered systolic blood pressure. However, when the same dose of nitrate-rich vegetables was co-ingested with thiocyanate-rich vegetables the increase in salivary [nitrite] was smaller and systolic blood pressure was not lowered. These findings might have implications for optimising dietary guidelines aimed at improving cardiovascular health., (Copyright © 2018. Published by Elsevier Inc.)