Biology subjects

Derbre, F.

Publications and source records attributed to Derbre, F..

3 recordsLinked to original sources

bioRxiv2026

Distinct iron metabolism regulation during cachexia progression in murine models of intestinal and pancreatic cancer

Background. Cancer cachexia is a multifactorial syndrome characterized by substantial metabolic disturbances including systemic inflammation, and muscle atrophy, which may affect the regulation of iron metabolism in patients. This study aimed to characterize this regulation in two murine models of colorectal and pancreatic cancer, both associated with a high prevalence of cachexia. Methods. Histological, biochemical and molecular analyses were performed in serum, skeletal muscle, liver, spleen and tumor from UN-KC-6141 pancreatic tumor bearing mice and from ApcMin/+ mice (colorectal cancer model), both models exhibiting variable cachexia severity. Results. Both models induce cachexia, but diverge markedly in their regulation of iron metabolism. UNKC mice display reduced plasma iron availability (-9.6% transferrin saturation, p<0.001) without concomitant anemia, while hepatic hepcidin synthesis is upregulated (+100.6%, p<0.001) by inflammation, promoting ferroportin (FPN) downregulation (-42.4%, p<0.001) and iron sequestration in the spleen (+134% total iron content, p<0.001). In the atrophied gastrocnemius, iron concentration is preserved through increased ferritin (+86.6%, p=0.010) and hemoproteins (i.e., myoglobin, CYSC, COXIV) expression. Conversely, ApcMin/+ mice exhibit anemia together with hepatic and splenic iron depletion (-48.4%, p<0.001 and -84.9%, p<0.001, respectively). Hepcidin synthesis is downregulated (-99.9%, p<0.001) despite persistent inflammation, indicating that hypoxia and/or iron-deficiency signals probably predominate over the inflammatory pathway. FPN is markedly decreased (-94.2%, p<0.001) in the iron-depleted spleen despite low hepcidin. In the atrophied quadriceps of ApcMin/+ mice, iron deficiency is associated with decreased FPN and ferritin (-87.9%, p<0.001, and -38.4%, p=0.016, respectively), and increased TfR1 expression (+305%, p=0.107). Finally, tumor iron import may play a significant role in cachexia progression, as suggested by the association between tumor weight, tumor TfR1 protein levels and body weight loss in UNKC mice. Conclusion. These findings reveal cancer type-specific signatures of iron regulation in cachexia, which appear to be more driven by cancer type specific features than by cachexia severity itself, with skeletal muscle iron metabolism impaired mainly when cachexia is associated with anemia. This suggests that the clinical management of iron metabolism in cachectic patients should be guided by the underlying cancer type.

physiology↗

bioRxiv2025

A conceptual framework for revealing minor bacterial signals inmicrobiome data through guided data transformation

The microbiome is a rich source of biological data that offers promising insights into personalized medicine. However, inferring host health from gut bacterial composition using statistical analytical methods remains a challenge. Here, we show that groups of bacterial species with high abundance and variance (referred to as dominant bacterial signals and often associated with enterotype) exert a disproportionately large influence on microbiome analyses, hiding the contribution of less expressed species (referred to as minor bacterial signals). To address this limitation, we propose a guided data transformation highlighting minor bacterial signals while minimizing the impact of dominant bacterial signals on microbiome statistical analyses. This transformation (i) leads to alternative clustering more closely associated with host health and (ii) helps to improve the performance of supervised machine learning algorithms in high-dimensional settings (n << p). Applying to a real dataset, our results suggest that dominant bacterial signals may act as a confounding variable to predict host health.

microbiology↗

bioRxiv2018

Skeletal muscle ceramides do not contribute to physical inactivity-induced insulin resistance

SUMMARY STATEMENTThis study supports that muscle ceramide do not play a key role in insulin resistance which developed early with physical inactivity.\n\nABSTRACTPhysical inactivity increases the risk to develop type 2 diabetes, a disease characterized by a state of insulin resistance. By promoting inflammatory state, ceramides are especially recognized to alter insulin sensitivity in skeletal muscle. The present study was designed to analyze, in mice, whether muscle ceramides contribute to physical inactivity-induced insulin resistance. For this purpose, we used the wheel lock model to induce a sudden reduction of physical activity, in combination with myriocin treatment, an inhibitor of de novo ceramide synthesis. Mice were assigned to 3 experimental groups: voluntary wheel access group (Active), a wheel lock group (Inactive) and wheel lock group treated with myriocin (Inactive-Myr). We observed that 10 days of physical inactivity induces hyperinsulinemia and increase HOMA-IR. The muscle ceramide content were not modified by physical inactivity and myriocin. Thus, muscle ceramides do not play a role in physical inactivity-induced insulin resistance. In skeletal muscle, insulin-stimulated Akt phosphorylation and inflammatory pathway were not affected by physical inactivity whereas a reduction of GLUT4 content was observed. Based on these results, physical inactivity-induced insulin resistance seems related to a reduction in GLUT4 content rather than defects in insulin signaling. We observed in inactive mice that myriocin treatment improved glucose tolerance, insulin-stimulated Akt, AMPK activation and GLUT4 content in skeletal muscle. Such effects occur regardless of changes in muscle ceramide content. These findings highlight that myriocin could be a promising drug to improve glucose tolerance and insulin sensitivity.

physiology↗