Glucose and lipopolysaccharide differentially regulate fibroblast growth factor 21 in healthy male human volunteers - A prospective cross-over trial.

Fibroblast growth factor 21 (FGF21) affects the regulation of metabolism. Additionally, anti-inflammatory properties are attributed to FGF21, and studies in animals and humans show conflicting results. This study aimed to investigate how FGF21 is affected by glucose and lipopolysaccharide (LPS) in humans. Therefore, FGF21 was measured eight times at different time points within 48 h in this prospective cross-over trial after glucose and LPS on two different study days. The study included ten healthy, non-smoking male subjects aged 18-40. Repeated measures analysis of variance and paired t-test as post hoc analysis were applied. The administration of glucose and LPS resulted in a significant difference in regulating FGF21 (p < 0.001). After glucose administration, FGF21 declined sharply at 360 min, with a subsequent steep increase that exceeded baseline levels. LPS induced a drop in FGF21 after 180 min, while the baseline concentrations were not reached. After 180 min and 24 h, a statistically significant difference was demonstrated after adjusting the Bonferroni-Holm method. So, our results support the hypothesis that glucose and LPS differentially affect the human expression of FGF21 over 48 h.

Effect of repeated bolus and continuous glucose infusion on a panel of circulating biomarkers in healthy volunteers.

HYPOTHESIS: Glycaemic variability (GV) refers to fluctuations in the blood glucose level and may contribute to complications in patients suffering from Diabetes. Several studies show negative effects of GV on the cardiovascular system, however there is still a lack of conclusive evidence. Using an explorative cardiovascular panel, it is possible to simultaneously measure the effects on proteins relevant for cardiovascular processes. The aim of this study was to investigate the effects of rapid glucose excursions on cardiovascular and metabolic parameters in healthy individuals. METHODS: An explorative single-blinded cross-over study was performed in ten healthy men. Subjects received 3 times 20 grams of glucose i.v. over 5 minutes or 60 grams of glucose continuously over 3 hours. Blood was taken for repeated measurements of the cardiovascular panel over the following 6 hours and again after 24 and 48 hours. RESULTS: We observed a significant elevation of 7 cardiovascular biomarkers (BMP6, SLAMF7, LOX-1, ADAMTS13, IL-1RA, IL-4RA, PTX3) at t = 360min after rapid glucose infusion compared to a continuous glucose infusion. CONCLUSIONS: Intraday GV seems to have acute effects on cardiovascular proteins in healthy test persons. Rapid glucose administration compared to continuous administration showed significant changes in BMP6, SLAMF7, ADAMTS13, IL1RA, PTX3, IL-4RA and LOX-1. CLINICAL TRIAL REGISTRATION: NCT04488848.

L-carnitine exerts a nutrigenomic effect via direct modulation of nuclear receptor signaling in adipocytes, hepatocytes and SKMC, demonstrating its nutritional impact.

L-carnitine is an indispensable metabolite facilitating the transport of fatty acids into the mitochondrial matrix and has been previously postulated to exert a nutrigenomic effect. However, the underlying molecular mechanisms remain mostly unclear. We hypothesized that L-carnitine interacts with nuclear receptors involved in metabolic regulation, thereby modulating downstream targets of cellular metabolism. Therefore, we investigated the effect of L-carnitine supplementation on protein activity, mRNA expression, and binding affinities of nuclear receptors as well as mRNA expression of downstream targets in skeletal muscle cells, hepatocytes, and differentiated adipocytes. L-carnitine supplementation to hepatocytes increased the protein activity of multiple nuclear receptors (RAR, RXR, VDR, PPAR, HNF4, ER, LXR). Diverging effects on the mRNA expression of PPAR-α, PPAR-δ, PPAR-γ, RAR-ß, LXR-α, and RXR-α were observed in adipocytes, hepatocytes, and skeletal muscle cells. mRNA levels of PPAR-α, a key regulator of lipolysis and ß-oxidation, were significantly upregulated, emphasizing a role of L-carnitine as a promoter of lipid catabolism. L-carnitine administration to hepatocytes modulated the transcription of key nuclear receptor target genes, including ALDH1A1, a promoter of adipogenesis, and OGT, a contributor to insulin resistance. Electrophoretic mobility shift assays proved L-carnitine to increase binding affinities of nuclear receptors to their promoter target sequences, suggesting a molecular mechanism for the observed transcriptional modulation. Overall, these findings indicate that L-carnitine modulates the activity and expression of nuclear receptors, thereby promoting lipolytic gene expression and decreasing transcription of target genes linked to adipogenesis and insulin resistance.

Clinical characterization of hospitalized COVID-19 patients during the second wave of pandemic in the district of Rohrbach, Upper Austria : A single center retrospective study.

During the peak of the second wave of the coronavirus disease 2019 (COVID-19) pandemic in November 2020, the district of Rohrbach, Upper Austria, was reported to have had the highest 7­day incidence of severe acute respiratory syndrome coronavirus­2 (SARS-CoV-2) positive cases worldwide. In this study, we present the clinical characteristics of COVID-19 cases during the second wave of the pandemic in patients admitted to the only primary care hospital in the district of Rohrbach between October 2020 and February 2021. In total, 260 patients were hospitalized with a mean age of 72 years and a mortality rate of 14.6% and 13 patients (5%) were transferred to the intensive care unit (ICU). Critically ill patients (22.7%) were of older age and often lived in retirement and nursing facilities as compared to mild or moderately ill patients. Patients with a severe disease course showed significantly longer hospitalization, a worse peripheral oxygen saturation on admission and significantly higher levels of C­reactive protein (CRP), procalcitonin (PCT), lactate dehydrogenase (LDH), troponin I and D­dimer as compared to mild or moderate COVID-19 cases. These laboratory parameters might help to identify COVID-19 patients with a severe disease course. In conclusion, we could show that older, frail individuals are the most vulnerable group affected by COVID-19. Whether this trend in hospitalized patients continues with the persistence of the pandemic, the emergence of novel virus mutations, and the availability of several different vaccines is presently unclear and remains to be determined.