Background A number of computational tools for metabolism prediction have been developed over the last 20 years to predict the structures of small molecules undergoing biological transformation or environmental degradation. These tools were largely developed to facilitate absorption, distribution, metabolism, excretion, and toxicity (ADMET) studies, although there is now a growing interest in using such tools to facilitate metabolomics and exposomics studies. However, their use and widespread adoption is still hampered by several factors, including their limited scope, breath of coverage, availability, and performance. Results To address these limitations, we have developed BioTransformer, a freely available software package for accurate, rapid, and comprehensive in silico metabolism prediction and compound identification. BioTransformer combines a machine learning approach with a knowledge-based approach to predict small molecule metabolism in human tissues (e.g. liver tissue), the human gut as well as the environment (soil and water microbiota), via its metabolism prediction tool. A comprehensive evaluation of BioTransformer showed that it was able to outperform two state-of-the-art commercially available tools (Meteor Nexus and ADMET Predictor), with precision and recall values up to 7 times better than those obtained for Meteor Nexus or ADMET Predictor on the same sets of pharmaceuticals, pesticides, phytochemicals or endobiotics under similar or identical constraints. Furthermore BioTransformer was able to reproduce 100% of the transformations and metabolites predicted by the EAWAG pathway prediction system. Using mass spectrometry data obtained from a rat experimental study with epicatechin supplementation, BioTransformer was also able to correctly identify 39 previously reported epicatechin metabolites via its metabolism identification tool, and suggest 28 potential metabolites, 17 of which matched nine monoisotopic masses for which no evidence of a previous report could be found. Conclusion BioTransformer can be used as an open access command-line tool, or a software library. It is freely available at https://bitbucket.org/djoumbou/biotransformerjar/ . Moreover, it is also freely available as an open access RESTful application at www.biotransformer.ca , which allows users to manually or programmatically submit queries, and retrieve metabolism predictions or compound identification data. Electronic supplementary material The online version of this article (10.1186/s13321-018-0324-5) contains supplementary material, which is available to authorized users.

-The aim of this study was to investigate whether treatment with tributyrin (Tb; a butyrate prodrug) results in protection against diet-induced obesity and associated insulin resistance. C57BL/6 male mice fed a standard chow or high-fat diet were treated with Tb (2 g/kg body wt, 10 wk) and evaluated for glucose homeostasis, plasma lipid profile, and inflammatory status. Tb protected mice against obesity and obesityassociated insulin resistance and dyslipidemia without food consumption being affected. Tb attenuated the production of TNF␣ and IL-1␤ by peritoneal macrophages and their expression in adipose tissue. Furthermore, in the adipose tissue, Tb reduced the expression of MCP-1 and infiltration by leukocytes and restored the production of adiponectin. These effects were associated with a partial reversion of hepatic steatosis, reduction in liver and skeletal muscle content of phosphorylated JNK, and an improvement in muscle insulin-stimulated glucose uptake and Akt signaling. Although part of the beneficial effects of Tb are likely to be secondary to the reduction in body weight, we also found direct protective actions of butyrate reducing TNF␣ production after LPS injection and in vitro by LPS-or palmitic acid-stimulated macrophages and attenuating lipolysis in vitro and in vivo. The results, reported herein, suggest that Tb may be useful for the treatment and prevention of obesity-related metabolic disorders.butyrate; macrophages; diabetes; cytokines; white adipose tissue THE CHRONIC LOW-GRADE INFLAMMATION associated with obesity plays a central role as a link between excessive fat accumulation and the development of pathologies (20). In obesity, adipose tissue is markedly infiltrated by proinflammatory macrophages and other leukocytes that secrete proinflammatory cytokines and chemokines (20,41,50). The overproduction of these inflammatory mediators together with changes in adipokine production and nonesterified fatty acid (NEFA) levels leads to the development of insulin resistance. In addition to adipose tissue, several organs, including the liver (1) and hypothalamus (28), develop a proinflammatory profile in response to the excessive nutrient supply. This systemic inflammatory state is associated with the activation of intracellular signaling pathways such as JUN NH 2 -terminal kinase (JNK) and IB kinase-␤ (IKK␤) that in turn phosphorylate serine residues in the insulin receptor substrate, inhibiting tyrosine phosphorylation and the interaction with phosphatidylinositol-3 kinase (19,21).In accord with an important role of inflammation in the development of obesity-associated diseases, whole body deletion of intracellular kinases activated upon inflammation, namely JNK (18) and IKK␤ (1), and pharmacological treatment with anti-inflammatory agents such as -3 fatty acids and salsalate, a salicylate derivate, were demonstrated to protect mice from the deleterious effects of high-fat feeding and obesity on insulin sensitivity (16,32).Butyrate is a short-chain fatty acid (SCFA) produced during fermentation o...

The aim of this study was to assess the effect of leucine supplementation on elements of the ubiquitin-proteasome system (UPS) in rat skeletal muscle during immobilization. This effect was evaluated by submitting the animals to a leucine supplementation protocol during hindlimb immobilization, after which different parameters were determined, including: muscle mass; cross-sectional area (CSA); gene expression of E3 ligases/deubiquitinating enzymes; content of ubiquitinated proteins; and rate of protein synthesis. Our results show that leucine supplementation attenuates soleus muscle mass loss driven by immobilization. In addition, the marked decrease in the CSA in soleus muscle type I fibers, but not type II fibers, induced by immobilization was minimized by leucine feeding. Interestingly, leucine supplementation severely minimized the early transient increase in E3 ligase [muscle ring finger 1 (MuRF1) and muscle atrophy F-box (MAFbx)/atrogin-1] gene expression observed during immobilization. The reduced peak of E3 ligase gene expression was paralleled by a decreased content of ubiquitinated proteins during leucine feeding. The protein synthesis rate decreased by immobilization and was not affected by leucine supplementation. Our results strongly suggest that leucine supplementation attenuates muscle wasting induced by immobilization via minimizing gene expression of E3 ligases, which consequently could downregulate UPS-driven protein degradation. It is notable that leucine supplementation does not restore decreased protein synthesis driven by immobilization.