Search Results (6)

Obesity is a complex disease highly related to diet and lifestyle and is associated with low amount of thermogenic adipocytes. Therapeutics that regulate brown adipocyte recruitment and activity represent interesting strategies to fight overweight and associated comorbidities. Recent studies suggest a role for several fatty acids and their metabolites, called lipokines, in the control of thermogenesis. The purpose of this work was to analyze the role of several lipokines in the control of brown/brite adipocyte formation. We used a validated human adipocyte model, human multipotent adipose-derived stem cell model (hMADS). In the absence of rosiglitazone, hMADS cells differentiate into white adipocytes, but convert into brite adipocytes upon rosiglitazone or prostacyclin 2 (PGI2) treatment. Gene expression was quantified using RT-qPCR and protein levels were assessed by Western blotting. We show here that lipokines such as 12,13-diHOME, 12-HEPE, 15dPGJ2 and 15dPGJ3 were not able to induce browning of white hMADS adipocytes. However, both fatty acid esters of hydroxy fatty acids (FAHFAs), 9-PAHPA and 9-PAHSA potentiated brown key marker UCP1 mRNA levels. Interestingly, CTA2, the stable analog of thromboxane A2 (TXA2), but not its inactive metabolite TXB2, inhibited the rosiglitazone and PGI2-induced browning of hMADS adipocytes. These results pinpoint TXA2 as a lipokine inhibiting brown adipocyte formation that is antagonized by PGI2. Our data open new horizons in the development of potential therapies based on the control of thromboxane A2/prostacyclin balance to combat obesity and associated metabolic disorders. Full article

Diabetes mellitus is a group of metabolic diseases characterized by hyperglycemia resulting from a defect in the production or function of insulin, secreted by β cells of the pancreatic islets. Pancreatic islets are spherical cell aggregates (100–200 μm) which consist of several cell types. What is most important for improving research in the field of diabetes is the development of a model that reflects in vivo conditions. Here, we present a study based on the Islet-on-a-chip system, which was designed to create fully functional pseudo-islets (three-dimensional aggregates of α and β cells). This PDMS/PDMS Islet-on-a-chip system consists of two elliptical cell-culture chambers. In each of the chambers, there are 15 round microtraps (280 μm × 280 μm), each of them composed of seven circular micropillars, which force cell aggregation by limiting the growth surface. We designed this device to facilitate the screening of potential therapeutic agents, so here, we examined the effect of the newly discovered compound named 5-PAHSA on the developed model. Due to the appropriate design of the microfluidic system, it was possible to simultaneously culture, observe, and analyze the cell proliferation, viability, and hormone expression after incubation using selected concentrations of 5-PAHSA. It was noticed that after incubation with 5-PAHSA, the degree of proliferation increased in relation to both the control and the previous day of incubation. After analysis of the fluorescence intensity levels, the highest expression of insulin was observed after 48h of incubation with 100 μm of 5-PAHSA. These observations were confirmed by analyzing the amounts of secreted insulin under low (LG, 2.5 mM) and high (HG, 16.5 mM) glucose conditions using the ELISA test. Based on these results, it can be concluded that 5-PAHSA has potential properties for use as a therapeutic agent in diabetes, and the developed microsystem can be used for rapid drug screening. Full article

Nowadays, diabetes mellitus is one of the most common chronic diseases in the world. Current research on the treatment of diabetes combines many fields of science, such as biotechnology, transplantology or engineering. Therefore, it is necessary to develop new therapeutic strategies and preventive methods. A newly discovered class of lipids—Palmitic Acid Hydroxy Stearic Acid (PAHSA) has recently been proposed as an agent with potential therapeutic properties. In this research, we used an islet-on-a-chip microfluidic 3D model of pancreatic islets (pseudoislets) to study two isomers of PAHSA: 5-PAHSA and 9-PAHSA as potential regulators of proliferation, viability, insulin and glucagon expression, and glucose-stimulated insulin and glucagon secretion. Due to the use of the Lab-on-a-chip systems and flow conditions, we were able to reflect conditions similar to in vivo. In addition, we significantly shortened the time of pseudoislet production, and we were able to carry out cell culture, microscopic analysis and measurements using a multi-well plate reader at the same time on one device. In this report we showed that under microfluidic conditions PAHSA, especially 5-PAHSA, has a positive effect on pseudoislet proliferation, increase in cell number and mass, and glucose-stimulated insulin secretion, which may qualify it as a compound with potential therapeutic properties. Full article

FSHD is caused by loss of silencing of the DUX4 gene, but the DUX4 protein has not yet been directly detected immunohistologically in affected muscle, raising the possibility that DUX4 expression may occur at time points prior to obtaining adult biopsies for analysis, with consequent perturbations of muscle being responsible for disease progression. To test the extent to which muscle can regenerate following DUX4-mediated degeneration, we employed an animal model with reversible DUX4 expression, the iDUX4pA;HSA mouse. We find that muscle histology does recover substantially after DUX4 expression is switched off, with the extent of recovery correlating inversely with the duration of prior DUX4 expression. However, despite fairly normal muscle histology, and recovery of most cytological parameters, the fibroadipogenic progenitor compartment, which is significantly elevated during bouts of fiber-specific DUX4 expression, does not return to basal levels, even many weeks after a single burst of DUX4 expression. We find that muscle that has recovered from a DUX4 burst acquires a propensity for severe fibrosis, which can be revealed by subsequent cardiotoxin injuries. These results suggest that a past history of DUX4 expression leads to maintained pro-fibrotic alterations in the cellular physiology of muscle, with potential implications for therapeutic approaches. Full article

Nonalcoholic fatty liver disease (NAFLD) is quickly becoming the most common liver disease worldwide. Within the NAFLD spectrum, patients with nonalcoholic steatohepatitis (NASH) are at the highest risk of developing cirrhosis and disease progression to hepatocellular carcinoma. To date, therapeutic options for NASH patients have been ineffective, and therefore, new options are urgently needed. Hence, a model system to develop new therapeutic interventions is needed. Here, we introduce two new in vitro models of steatosis induction in HepG2 cells and primary murine hepatocytes. We used a recently discovered novel class of bioactive anti-inflammatory lipids called branched fatty acid esters of hydroxyl fatty acids. Among these bioactive lipids, palmitic-acid-9-hydroxy-stearic-acid (9-PAHSA) is the most promising as a representative nondrug therapy based on dietary supplements or nutritional modifications. In this study, we show a therapeutic effect of 9-PAHSA on lipotoxicity in steatotic primary hepatocytes and HepG2 cells. This could be shown be increased viability and decreased steatosis. Furthermore, we could demonstrate a preventive effect in HepG2 cells. The outcome of 9-PAHSA administration is both preventative and therapeutically effective for hepatocytes with limited damage. In conclusion, bioactive lipids like 9-PAHSA offer new hope for prevention or treatment in patients with fatty liver and steatosis. Full article

Polycyclic aromatic hydrocarbons (PAHs)—a large group of organic compounds—are extremely hazardous to human health. In this study, the 198 samples from six groups of daily food products in the Hanoi metropolitan area were collected and prepared by the QuEChERS sample treatment technique. The detection and identification of PAHs were obtained by gas chromatography–tandem mass spectrometry (GC–MS/MS) determination. The results demonstrated that the recovery of PAH compounds ranged approximately between 71% and 110% when the solvent evaporation condition was optimized using the nitrogen gas at a low temperature (1 °C). The in-house method was validated in terms of linearity, extractive condition, repeatability, recovery, limit of detection (LOD), and limit of quantification (LOQ). The ranges of average PAH levels were 9.3–9.6 µg/kg (for instant noodles), 0.22–2.48 µg/kg (for cakes) 0.91–4.83 µg/kg (dried vegetables), 5.14–23.32 µg/kg (teas), 4.82–24.35 µg/kg (coffees), and 1.43–25.2 µg/kg (grilled meats). The results indicated that the total concentrations of residual PAHs and benzo(a)pyrene in the instant noodles and grilled meat samples surpassed the maximum limits tolerated by the European Commission (35 µg/kg and 5 µg/kg, respectively) in many investigated samples. Full article