Background In 1957, Francis Crick drew a linear diagram on a blackboard. This diagram is often called the “central dogma.” Subsequently, the relationships between different steps of the “central dogma” have been shown to be considerably complex, mostly because of the emerging world of small molecules. It is noteworthy that metabolites can be generated from the diet through gut microbiome metabolism, serve as substrates for epigenetic modifications, destabilize DNA quadruplexes, and follow Lamarckian inheritance. Small molecules were once considered the missing link in the “central dogma”; however, recently they have acquired a central role, and their general perception as downstream products has become reductionist. Metabolomics is a large-scale analysis of metabolites, and this emerging field has been shown to be the closest omics associated with the phenotype and concomitantly, the basis for all omics. Aim of review Herein, we propose a broad updated perspective for the flux of information diagram centered in metabolomics, including the influence of other factors, such as epigenomics, diet, nutrition, and the gut- microbiome. Key scientific concepts of review Metabolites are the beginning and the end of the flux of information.

Metabolomics is the last frontier of modern molecular biology, and the state-of-the-art technique for studying metabolism. Mass spectrometry and nuclear magnetic resonance spectroscopy are the main analytical approaches in metabolomics. Cellular metabolism plays a pivotal role during cell resting and activation. Immune cells exhibit remarkable metabolic plasticity, fundamental to support their adaptation to inflammatory environments and functional requirements. Cancer is a metabolic and inflammatory disease. A metabolic shift is crucial for oncogenesis, tumor cell survival, invasion, metastasis, and the associated inflammatory process. The tumor microenvironment is mainly orchestrated by immune-inflammatory cells and essential for the neoplastic process. Inflammatory cells from tumor stroma adapt to different metabolic pathways during tumor progression, and this metabolic reprogramming affects macrophages, neutrophils, T cells, and others. Targeting the metabolism of tumor and immune cells may lead to important therapeutic implications in cancer. Thus, understanding the metabolic changes that drive the interactions between tumor and stromal cells is a promising avenue advances in cancer diagnostics and therapies, leading to more accurate guidance. In this review, we discuss the most recent metabolomics approaches in cancer studies on the tumor-associated inflammatory microenvironment.

In obesity, high levels of TNF-α in the bone marrow microenvironment induces the bone marrow-mesenchymal stem cells (BM-MSCs) towards a pro-adipogenic phenotype. Here, we investigated the effect of obesity on the migratory potential of BM-MSCs and their fate towards the adipose tissues. BM-MSCs were isolated from male C57Bl/06 mice with high-fat diet-induced obesity. The migratory potential of the BM-MSCs, their presence in the subcutaneous (SAT) and the visceral adipose tissues (VAT), and the possible mechanisms involved were investigated. Obesity did not affect MSC content in the bone marrow but increased the frequency of MSCs in blood, SAT, and VAT. In these animals, the SAT adipocytes presented a larger area, without any changes in adipokine production or the SDF-1α gene expression. In contrast, in VAT, obesity increased leptin and IL-10 levels but did not modify the size of the adipocytes. The BM-MSCs from obese animals presented increased spontaneous migratory activity. Despite the augmented expression of CXCR4, these cells exhibited decreased migratory response toward SDF-1α, compared to that of BM-MSCs from lean mice. The PI3K-AKT pathway activation seems to mediate the migration of BM-MSCs from lean mice, but not from obese mice. Additionally, we observed an increase in the spontaneous migration of BM-MSCs from lean mice when they were co-cultured with BM-HCs from obese animals, suggesting a paracrine effect. We concluded that obesity increased the migratory potential of the BM-MSCs and induced their accumulation in VAT, which may represent an adaptive mechanism in response to chronic nutrient overload.