Collagen I Increases Palmitate-Induced Lipotoxicity in HepG2 Cells via Integrin-Mediated Death.

Various strategies have been employed to improve the reliability of 2D, 3D, and co-culture in vitro models of nonalcoholic fatty liver disease, including using extracellular matrix proteins such as collagen I to promote cell adhesion. While studies have demonstrated the significant benefits of culturing cells on collagen I, its effects on the HepG2 cell line after exposure to palmitate (PA) have not been investigated. Therefore, this study aimed to assess the effects of PA-induced lipotoxicity in HepG2 cultured in the absence or presence of collagen I.

The role of adipogenic capacity and dysfunctional subcutaneous adipose tissue in the inheritance of type 2 diabetes mellitus: cross-sectional study.

Objective: This study tested the hypothesis that limited subcutaneous adipose tissue (SAT) expansion represents a primary predisposition to the development of type 2 diabetes mellitus (T2DM), independent of obesity, and identified novel markers of SAT dysfunction in the inheritance of T2DM.

Methods: First-degree relatives (FDR) of T2DM patients (n = 19) and control individuals (n = 19) without obesity (fat mass < 25%) were cross-sectionally compared. Body composition (bioimpedance, computed tomography) and insulin sensitivity (IS; oral glucose tolerance test, clamp) were measured.

Comparison of HepaRG and HepG2 cell lines to model mitochondrial respiratory adaptations in non‑alcoholic fatty liver disease.

Although some clinical studies have reported increased mitochondrial respiration in patients with fatty liver and early non‑alcoholic steatohepatitis (NASH), there is a lack of models of non‑alcoholic fatty liver disease (NAFLD) with similar findings. Despite being the most commonly used immortalized cell line for models of NAFLD, HepG2 cells exposed to free fatty acids (FFAs) exhibit a decreased mitochondrial respiration. On the other hand, the use of HepaRG cells to study mitochondrial respiratory changes following exposure to FFAs has not yet been fully explored.

The bisphenol S contamination level observed in human follicular fluid affects the development of porcine oocytes.

Bisphenol S (BPS), the main replacement for bisphenol A (BPA), is thought to be toxic, but limited information is available on the effects of Bisphenol S on ovarian follicles. In our study, we demonstrated the presence of Bisphenol S in the follicular fluid of women at a concentration of 22.4 nM.

Muscle Lipid Oxidation Is Not Affected by Obstructive Sleep Apnea in Diabetes and Healthy Subjects.

The molecular mechanisms linking obstructive sleep apnea (OSA) with type 2 diabetes mellitus (T2DM) remain unclear. This study investigated the effect of OSA on skeletal muscle lipid oxidation in nondiabetic controls and in type 2 diabetes (T2DM) patients. Forty-four participants matched for age and adiposity were enrolled: nondiabetic controls (control, = 14), nondiabetic patients with severe OSA (OSA, = 9), T2DM patients with no OSA (T2DM, = 10), and T2DM patients with severe OSA (T2DM + OSA, = 11).

Isoprenaline modified the lipidomic profile and reduced β-oxidation in HL-1 cardiomyocytes: model of takotsubo syndrome.

Recent studies have suggested a pathogenetic link between impaired mitochondria and Takotsubo syndrome (TTS), which is closely connected with catecholamine overstimulation, poor outcomes, and changes in lipid metabolism. We investigated the changes in lipid metabolism at the level of fatty acid β-oxidation and changes in the intracellular lipidomic spectrum. The immortalized cell line of HL-1 cardiomyocytes was used in this study as an established model of TTS.

The Effect of Chronic Exposure of Graphene Nanoplates on the Viability and Motility of A549 Cells.

Graphene and its derivatives are popular nanomaterials used worldwide in many technical fields and biomedical applications. Due to such massive use, their anticipated accumulation in the environment is inevitable, with a largely unknown chronic influence on living organisms. Although repeatedly tested in chronic in vivo studies, long-term cell culture experiments that explain the biological response to these nanomaterials are still scarce.

Measuring Mitochondrial Substrate Flux in Recombinant Perfringolysin O-Permeabilized Cells.

Mitochondrial substrate flux is a distinguishing characteristic of each cell type, and changes in its components such as transporters, channels, or enzymes are involved in the pathogenesis of several diseases. Mitochondrial substrate flux can be studied using intact cells, permeabilized cells, or isolated mitochondria. Investigating intact cells encounters several problems due to simultaneous oxidation of different substrates.

Western Diet Decreases the Liver Mitochondrial Oxidative Flux of Succinate: Insight from a Murine NAFLD Model.

Mitochondria play an essential role in the pathogenesis of nonalcoholic fatty liver disease (NAFLD). Previously, we found that succinate-activated respiration was the most affected mitochondrial parameter in mice with mild NAFLD. In this study, we focused on the role of succinate dehydrogenase (SDH) in NAFLD pathogenesis.

Effect of Maternal Preeclampsia on Hematological Profile of Newborns in Qatar.

Background: Preeclampsia is a major cause of pregnancy-related maternal, fetal, and neonatal morbidities and mortalities. We aimed to review the effect of maternal preeclampsia on the hematological profile of newborns in the Qatari population.

Methods: In this case-control study, we reviewed data and complete blood count results of neonates born to Qatari women diagnosed of preeclampsia in 2017 in comparison with data of a control group.

Dose-dependent regulation of mitochondrial function and cell death pathway by sorafenib in liver cancer cells.

Hepatocellular carcinoma (HCC) is the most common type of primary liver cancer and the fourth most frequent cause of cancer-related death worldwide. Sorafenib is the first line recommended therapy for patients with locally advanced/metastatic HCC. The low response rate is attributed to intrinsic resistance of HCC cells to Sorafenib.

Mixed copper(ii)-phenanthroline complexes induce cell death of ovarian cancer cells by evoking the unfolded protein response.

There is an ongoing need for the development of new cancer therapeutics that combine high cytotoxic efficiency with low side effects, and also override resistance to the first-line chemotherapeutics. Copper(ii)-phenanthroline complexes are promising compounds that were shown previously to induce an immediate cytotoxic response over a panel of tumor cell lines in vitro. The molecular mechanism, however, remained unresolved.

Expression of lipogenic markers is decreased in subcutaneous adipose tissue and adipocytes of older women and is negatively linked to GDF15 expression.

In aging, the capacity of subcutaneous adipose tissue (SAT) to store lipids decreases and this results in metabolically unfavorable fat redistribution. Triggers of this age-related SAT dysfunction may include cellular senescence or endoplasmic reticulum (ER) stress. Therefore, we compared lipogenic capacity of SAT between young and older women and investigated its relation to senescence and ER stress markers.

The Effect of Hypoxia and Metformin on Fatty Acid Uptake, Storage, and Oxidation in L6 Differentiated Myotubes.

Metabolic impairments associated with obstructive sleep apnea syndrome (OSA) are linked to tissue hypoxia, however, the explanatory molecular and endocrine mechanisms remain unknown. Using gas-permeable cultureware, we studied the chronic effects of mild and severe hypoxia on free fatty acid (FFA) uptake, storage, and oxidation in L6 myotubes under 20, 4, or 1% O. Additionally, the impact of metformin and the peroxisome proliferator-activated receptor (PPAR) β/δ agonist, called GW501516, were investigated.

Metabolic stress regulates ERK activity by controlling KSR-RAF heterodimerization.

Altered cell metabolism is a hallmark of cancer, and targeting specific metabolic nodes is considered an attractive strategy for cancer therapy. In this study, we evaluate the effects of metabolic stressors on the deregulated ERK pathway in melanoma cells bearing activating mutations of the or oncogenes. We report that metabolic stressors promote the dimerization of KSR proteins with CRAF in NRAS-mutant cells, and with oncogenic BRAF in BRAF-mutant cells, thereby enhancing ERK pathway activation.

Effects of Propofol on Cellular Bioenergetics in Human Skeletal Muscle Cells.

Objectives: Propofol may adversely affect the function of mitochondria and the clinical features of propofol infusion syndrome suggest that this may be linked to propofol-related bioenergetic failure. We aimed to assess the effect of therapeutic propofol concentrations on energy metabolism in human skeletal muscle cells.

Design: In vitro study on human skeletal muscle cells.

Chronic dietary exposure to branched chain amino acids impairs glucose disposal in vegans but not in omnivores.

Background/objectives: Branched chain amino acids (BCAA) are among nutrients strongly linked with insulin sensitivity (IS) measures. We investigated the effects of a chronic increase of BCAA intake on IS in two groups of healthy subjects differing in their basal consumption of BCAA, that is, vegans and omnivores.

Subjects/methods: Eight vegans and eight matched omnivores (five men and three women in each group) received 15 g (women) or 20 g (men) of BCAA daily for 3 months.

Mitochondrial Probe Methyltriphenylphosphonium (TPMP) Inhibits the Krebs Cycle Enzyme 2-Oxoglutarate Dehydrogenase.

Methyltriphenylphosphonium (TPMP) salts have been widely used to measure the mitochondrial membrane potential and the triphenylphosphonium (TPP+) moiety has been attached to many bioactive compounds including antioxidants to target them into mitochondria thanks to their high affinity to accumulate in the mitochondrial matrix. The adverse effects of these compounds on cellular metabolism have been insufficiently studied and are still poorly understood. Micromolar concentrations of TPMP cause a progressive inhibition of cellular respiration in adherent cells without a marked effect on mitochondrial coupling.

Adipogenesis, lipogenesis and lipolysis is stimulated by mild but not severe hypoxia in 3T3-L1 cells.

In-vitro investigation of the effects of hypoxia is limited by physical laws of gas diffusion and cellular O2 consumption, making prolonged exposures to stable O2 concentrations impossible. Using a gas-permeable cultureware, chronic effects of mild and severe hypoxia on triglyceride accumulation, lipid droplet size distribution, spontaneous lipolysis and gene expression of adipocyte-specific markers were assessed. 3T3-L1 cells were differentiated under 20%, 4% or 1% O2 using a gas-permeable cultureware.

The Effect of Pericellular Oxygen Levels on Proteomic Profile and Lipogenesis in 3T3-L1 Differentiated Preadipocytes Cultured on Gas-Permeable Cultureware.

Pericellular oxygen concentration represents an important factor in the regulation of cell functions, including cell differentiation, growth and mitochondrial energy metabolism. Hypoxia in adipose tissue has been associated with altered adipokine secretion profile and suggested as a possible factor in the development of type 2 diabetes. In vitro experiments provide an indispensable tool in metabolic research, however, physical laws of gas diffusion make prolonged exposure of adherent cells to desired pericellular O2 concentrations questionable.

Mitochondrial function in skeletal muscle of patients with protracted critical illness and ICU-acquired weakness.

Background: Mitochondrial damage occurs in the acute phase of critical illness, followed by activation of mitochondrial biogenesis in survivors. It has been hypothesized that bioenergetics failure of skeletal muscle may contribute to the development of ICU-acquired weakness. The aim of the present study was to determine whether mitochondrial dysfunction persists until protracted phase of critical illness.

The effect of cultureware surfaces on functional and structural components of differentiated 3T3-L1 preadipocytes.

Experiments using cultured primary cells or cell lines are a routine in vitro approach used across multiple biological disciplines, However, the structural and functional influences of various cultureware materials on cultured cells is not clearly understood. Surface treatments of cultureware have proven to have profound effects on cell viability and proliferation. In this study, we investigated the impact of polystyrene and fluorocarbon cultureware dishes on the proteomic profile of differentiated 3T3-L1 preadipocytes.

Lipophilic triphenylphosphonium cations inhibit mitochondrial electron transport chain and induce mitochondrial proton leak.

Background: The lipophilic positively charged moiety of triphenylphosphonium (TPP+) has been used to target a range of biologically active compounds including antioxidants, spin-traps and other probes into mitochondria. The moiety itself, while often considered biologically inert, appears to influence mitochondrial metabolism.

Methodology/principal Findings: We used the Seahorse XF flux analyzer to measure the effect of a range of alkylTPP+ on cellular respiration and further analyzed their effect on mitochondrial membrane potential and the activity of respiratory complexes.