Naphthenic Acid Fraction Components-Induced Metabolic and Mitochondrial Alterations in Rat Hepatoma Cells: Monitoring Metabolic Reprogramming with Tryptophan–Kynurenine Ratio
Why this work is in the frame
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Bibliographic record
Abstract
Altered body condition and diminished growth in wildlife in the Alberta Oil Sands Region (AOSR) are prompting investigations into the impact of oil sands industrial activity on wildlife in the region. Chemical constituents from bitumen-influenced waters, including oil sands process-affected water (OSPW), can disrupt endocrine signaling, leading to aberrant lipid accumulation and altered glycemic control in mammals. This study aimed to investigate the effects of naphthenic acid fraction components (NAFCs), derived from OSPW, on energy homeostasis using the McA-RH7777 rat hepatocyte model. Cells were exposed to NAFCs at nominal concentrations of 0, 0.73, 14.7, and 73.4 mg/L for 24 and 48 h. We assessed gene expression related to lipid and glucose metabolism and measured triglyceride accumulation, glucose, and fatty acid uptake. NAFC exposure (14.7 and 73.4 mg/L) reduced triglyceride levels and glucose uptake and increased fatty acid uptake and the expression of beta-oxidation genes, suggesting a metabolic switch from glucose to fatty acid oxidation. This switch in substrate availability signifies a shift in cellular energy dynamics, potentially linked to altered mitochondrial function. To investigate this, we conducted adenosine triphosphate (ATP), mitochondrial membrane potential, and terminal deoxynucleotidyl transferase dUTP nick-end labeling (TUNEL) assays to measure cellular ATP levels, mitochondrial membrane potential, and apoptosis, respectively. At both time points, 73.4 mg/L NAFC exposure resulted in increased ATP levels, induced mitochondrial membrane hyperpolarization, and increased apoptosis. These results suggest that mitochondrial efficiency is compromised, necessitating metabolic adaptations to maintain energy homeostasis. Given that cells exhibit metabolic flexibility that allows them to dynamically respond to changes in substrate availability, we further demonstrated that the kynurenine-tryptophan ratio (KTR) serves as a marker for a shift in energy metabolism under these stress conditions. This work provides a mechanistic framework for understanding how bitumen-derived organic contaminants may disrupt metabolic function in wildlife living in the AOSR. These findings further support the use of molecular markers like KTR to evaluate sub-lethal metabolic stress in environmental health monitoring.
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Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.000 |
| Bibliometrics | 0.000 | 0.001 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.001 |
| Insufficient payload (model declined to judge) | 0.000 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from it