Although a role for endoglin in ECM regulation had been previously suggested this conclusion was obtained the insulin-mediated suppression

In agreement, the non-nutritive sweetener D-tagatose has previously been found to elevate propionate levels in the lower large intestine of pigs. From a dietary perspective, small amounts of APM as well as its decomposition products may reach the colon, influencing the gut microbiota. APM is quickly hydrolyzed in the intestine into methanol, phenylalanine, and aspartate, as previously mentioned. The systemic concentrations of these metabolites are thought to remain unchanged post consumption based on studies underlying the statement that APM is considered safe at “current levels of exposure”, as stated by the European Food Safety Authority. In agreement, our serum metabolomics analysis showed no difference in APM breakdown products between treatments, evidence of the small dose of APM ingested, and that the compound was rapidly metabolized and excreted by rats. Of these components, not all are absorbed in the small intestine, hence some make their way to the colon where they can be fermented by the gut microbiota. The presence of such compounds could potentially explain the alterations in the gut microbiota seen in the APM animals. Of note, none of these dipeptides were detectable by the metabolomics method employed in this study. In summary, results of this study show APM to mitigate many of the negative effects associated with HF feeding including lower body mass, adiposity, caloric consumption and fasting insulin levels. In spite of this, APM resulted in hyperglycemia and an impaired ability to respond to insulin, which could be due to enhanced gluconeogenesis fueled by production of the SCFA propionate by the gut microbiota. This mechanism warrants future investigation and may explain the increased risk of metabolic disease states with regular APM consumption observed in population-based studies. In previous studies, we have observed that endoglin expression was increased in different experimental models of renal fibrosis. Furthermore, endoglin haploinsufficiency does not seem to affect the fibrosis induced in the UUO model. As the expression of the different membrane endoglin isoforms was not assessed in those experiments, and it has been Remdesivir AbMole reported that L- and S-Endoglin show distinct modulatory effects on TGF-b signaling, the contribution of endoglin and its isoforms to renal fibrosis remains unclear. In this study, our aim has been to evaluate if the overexpression of L-Endoglin, the predominant endoglin isoform, modulates renal fibrosis after UUO. Our results are in agreement with several authors that have shown a profibrotic role of endoglin in different fibrotic contexts such as kidney after irradiation and heart after thoracic aorta constriction.

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