Coumestrol is a phytoestrogen widely known for its anti-diabetic, anti-oxidant, and anti-inflammatory properties. Thus, it gets a lot of attention as a potential agent in the nutritional therapy of diseases such as obesity and type 2 diabetes. In our study, we evaluated whether coumestrol affects insulin resistance development via the sphingolipid signaling pathway in primary rat hepatocytes. The cells were isolated from the male Wistar rat’s liver with the use of collagenase perfusion. Next, we incubated the cells with the presence or absence of palmitic acid and/or coumestrol. Additionally, some groups were incubated with insulin. The sphingolipid concentrations were assessed by HPLC whereas the expression of all the proteins was evaluated by Western blot. Coumestrol markedly reduced the accumulation of sphingolipids, namely, ceramide and sphinganine through noticeable inhibition of the ceramide de novo synthesis pathway in insulin-resistant hepatocytes. Moreover, coumestrol augmented the expression of fatty acid transport proteins, especially FATP5 and FAT/CD36, which also were responsible for excessive sphingolipid accumulation. Furthermore, coumestrol altered the sphingolipid salvage pathway, which was observed as the excessive deposition of the sphingosine-1-phosphate and sphingosine. Our study clearly showed that coumestrol ameliorated hepatic insulin resistance in primary rat hepatocytes. Thus, we believe that our study may contribute to the discovery of novel preventive and therapeutic methods for metabolic disorders.

Endometrial cancer (EC) is one of the most frequent female malignancies. Because of a characteristic symptom, vaginal bleeding, EC is often diagnosed in an early stage. Despite that, some EC cases present an atypical course with rapid progression and poor prognosis. There have been multiple studies conducted on molecular profiling of EC in order to improve diagnostics and introduce personalized treatment. Chemokines—a protein family that contributes to inflammatory processes that may promote carcinogenesis—constitute an area of interest. Some chemokines and their receptors present alterations in expression in tumor microenvironment. CXCL12, which binds the receptors CXCR4 and CXCR7, is known for its impact on neoplastic cell proliferation, neovascularization and promotion of epidermal–mesenchymal transition. The CCL2–CCR2 axis additionally plays a pivotal role in EC with mutations in the LKB1 gene and activates tumor-associated macrophages. CCL20 and CCR6 are influenced by the RANK/RANKL pathway and alter the function of lymphocytes and dendritic cells. Another axis, CXCL10–CXCR3, affects the function of NK-cells and, interestingly, presents different roles in various types of tumors. This review article consists of analysis of studies that included the roles of the aforementioned chemokines in EC pathogenesis. Alterations in chemokine expression are described, and possible applications of drugs targeting chemokines are reviewed.

Ovarian cancer is the seventh most common cancer in women. It is characterized by a high mortality rate because of its aggressiveness and advanced stage at the time of diagnosis. It is a nonhomogenous group of neoplasms and, of which the molecular basics are still being investigated. Nowadays, the golden standard in the treatment is debulking cytoreductive surgery combined with platinum-based chemotherapy. We have presented the interactions and the resulting perspectives between fatty acid transporters, glucose transporters and ovarian cancer cells. Studies have shown the association between a lipid-rich environment and cancer progression, which suggests the use of correspondent transporter inhibitors as promising chemotherapeutic agents. This review summarizes preclinical and clinical studies highlighting the role of fatty acid transport proteins and glucose transporters in development, growth, metastasizing and its potential use in targeted therapies of ovarian cancer.

Rapidly increasing worldwide prevalence of obesity and related pathologies encompassing coronary heart disease, hypertension, metabolic syndrome, or type 2 diabetes constitute serious threats to global health and are associated with a significantly elevated risk of premature death. Considering the enormous burden of these pathologies, novel therapeutic and preventive patterns are indispensable. Dysregulation of one of the most complex biological systems in the human body namely, the endocannabinoid system (ECS) may result in metabolic imbalance and development of insulin resistance, type 2 diabetes, or non-alcoholic fatty liver disease. Furthermore, many studies showed that physical exercises, depending on their type, intensity, and frequency, exert various alterations within the ECS. Emerging evidence suggests that targeting the ECS via physical activity may produce robust beneficial effects on the course of metabolic pathologies. However, the data showing a direct correlation between the ECS and physical activity in the aspect of metabolic health are very scarce. Therefore, the aim of this review was to provide the most up-to-date state of knowledge about the interplay between the ECS activity and physical exercises in the novel therapeutic and preventive approach toward metabolic pathologies. We believe that this paper, at least in part, will fulfill the existing gap in knowledge and encourage researchers to further explore this very complex yet interesting link between the ECS, its action in physical activity, and subsequent positive outcomes for metabolic health.

Vitamin K2 (VK2) is one of the two types of vitamin K present most in the human diet. VK2 seems to have a beneficial effect on inflammation related to type 2 diabetes mellitus. The aim of this study was to evaluate the influence of VK2 on lipid precursors of inflammation in lipid-overloaded human liver hepatocellular carcinoma cells. Cells were incubated with VK2 and/or palmitic acid (PA). The concentrations of lipid fractions and their fatty acid compositions were measured by gas-liquid chromatography. The expression of proteins involved in the inflammatory process was detected using western blotting. The concentration of triacylglycerols (TAGs), activities of the n-3 pathway in TAGs, and lipooxygenase 15 expression were significantly elevated in cells incubated with PA and VK2. In the same group, a marked elevation in diacylglycerol (DAG) 20:4 was observed. VK2 supplementation lowered the expression of tumour necrosis factor-alpha and interleukin-6 compared to that in the PA group. The data indicate that VK2 redirects fatty acid metabolism into the deposition of a safe TAG fraction by increasing the concentration of anti-inflammatory n-3 polyunsaturated fatty acids in this fraction. Moreover, VK2 stimulates the synthesis of anti-inflammatory factors and has anti-inflammatory effects by reducing DAG 20:4.

Metabolic-Associated Fatty Liver Disease (MAFLD) is a major cause of liver diseases globally and its prevalence is expected to grow in the coming decades. The main cause of MAFLD development is changed in the composition of the extracellular matrix (ECM). Increased production of matrix molecules and inflammatory processes lead to progressive fibrosis, cirrhosis, and ultimately liver failure. In addition, increased accumulation of sphingolipids accompanied by increased expression of pro-inflammatory cytokines in the ECM is closely related to lipogenesis, MAFLD development, and its progression to fibrosis. In our work, we will summarize all information regarding the role of sphingolipids e.g., ceramide and S1P in MAFLD development. These sphingolipids seem to have the most significant effect on macrophages and, consequently, HSCs which trigger the entire cascade of overproduction matrix molecules, especially type I and III collagen, proteoglycans, elastin, and also tissue inhibitors of metalloproteinases, which as a result cause the development of liver fibrosis.