Biology subjects

Melin, V.

Publications and source records attributed to Melin, V..

4 recordsLinked to original sources

bioRxiv2025

Multiple pathways prevent bi-parental mitochondria transmission in C. elegans

The uniparental transmission of the maternal mitochondrial genome is achieved by the disposal of the sperm mitochondria and their DNA (mtDNA) around fertilization. C. elegans embryo allowed the identification of several factors and mechanisms involved after fertilization. The discovery that the autophagy pathway and its adaptor ALLO-1 are implicated represented a major progress. In addition, studies in fish and fly have implicated CPS-6, a sperm mitochondrial endonuclease, in the degradation of C. elegans sperm-derived mtDNA. The sperm mitochondria-associated proteins FNDC-1 and PHB-2 were also implicated in efficiently removing sperm-derived mitochondria. Despite these recent findings, it is still not clear whether they account for the complete degradation and if we can experimentally prevent sperm-mitochondria clearance and induce sperm-mtDNA transmission to the progeny. Here, we investigated the genetic interactions and tested the impact of simultaneous inactivation of known factors on the fate of sperm-derived mitochondria and their mtDNA. We revealed an additive effect of ALLO-1 and CPS-6 loss of function. Furthermore, the inactivation of known factors acting in sperm mitochondria clearance was not sufficient to avoid sperm mitochondria removal and to allow paternal mtDNA inheritance across generations. These findings reveal that C. elegans employs at least two parallel pathways to ensure the degradation of paternal mitochondria and suggest the presence of unidentified mechanism(s) safeguarding maternal mitochondrial inheritance.

developmental biology↗

bioRxiv2024

Effect of thermoneutral housing on MASLD severity, hepatic gene expression, and BAT activation during beta3-adrenergic stimulation in mice

Metabolic dysfunction-associated steatotic liver disease (MASLD), and its more advanced stage metabolic dysfunction-associated steatohepatitis, is the most common chronic liver disease, constituting a major public health issue. No medication is approved for MASLD treatment, and relevant preclinical models are needed to define molecular mechanisms underlying MASLD pathogenesis, and evaluate therapeutic approaches. Here we demonstrated that compared to standard temperature housing, thermoneutral housing aggravated western diet (WD)-induced obesity, diabetes, and steatosis in male mice, which was associated with increased hepatic expression of inflammation- and fibrosis-related genes. Accordingly, compared to standard-housed mice, thermoneutral-housed WD-fed mice developed more severe hepatic inflammation and fibrosis. The liver is the central metabolic organ in whole-body metabolic homeostasis. We used thermoneutrally housed mice with WD-induced MASLD to examine the effect of MASLD during {beta}3- adrenergic stimulation, and found that diet-induced MASLD was associated with defective inter- organ metabolic cross-talk, leading to impaired brown adipose tissue activation. HighlightsO_LIThermoneutral housing promotes WD-induced obesity and MASLD in mice C_LIO_LIThermoneutral housing fosters WD-induced change in gene expression C_LIO_LIThermoneutral housing fosters hepatic inflammation and fibrosis C_LIO_LIMASLD is associated with defective BAT response to {beta}3-adrenergic stimulation C_LI

physiology↗

bioRxiv2023

Behavioral Thermoregulation in Captive Fish: Molecular, Physiological, and Welfare Implications

Environmental Enrichment (EE) serves as a cornerstone in the attempt to emulate natural habitats for captive organisms. While substantial strides have been made in this field, current methodologies still grapple with discrepancies between recreated habitats and the innate conditions vital for maintaining biological homeostasis in captive species. Our study highlights the pivotal role of behavioral thermoregulation in modulating molecular and physiological outcomes in captive fish. Collective evidence suggests that enabling fish to autonomously regulate temperature confers numerous beneficial cellular and systemic effects. Specifically, introducing a thermal gradient within the EE paradigm correlated with increased survival metrics, enhanced physiological parameters, and improved welfare indices, establishing the criticality of thermoregulation in captivity. In contrast, the lack of a thermoregulatory framework resulted in the emergence of transient free radicals, a clear marker of temperature-induced oxidative stress. Persistent disruptions in free radical equilibrium, especially in uniform temperature settings, were linked to DNA damage, heightened cellular apoptosis, tissue anomalies, and metabolic deviations. In conclusion, this research underscores the significance of behavioral thermoregulation as an integral feature of EE, especially related to fish in controlled environments. Our data present key biomarkers valuable for optimizing fish welfare and highlight the necessity for sustained research into their adaptability and survival benchmarks. Such insights aim to enhance EE protocols, fortifying their efficacy in mirroring natural habitats and, in turn, advancing the welfare benchmarks of captive organisms.

physiology↗

bioRxiv2021

ATGL-dependent white adipose tissue lipolysis controls hepatocyte PPARα activity

ObjectiveIn hepatocytes, peroxisome proliferator-activated receptor (PPAR) acts as a lipid sensor that regulates hepatic lipid catabolism during fasting and orchestrates a genomic response required for whole-body homeostasis. This includes the biosynthesis of ketone bodies and the secretion of the starvation hormone fibroblast growth factor 21 (FGF21). Several lines of evidence suggest that adipose tissue lipolysis contributes to this specific process. However, whether adipose tissue lipolysis is a dominant signal for the extensive remodeling of liver gene expression dependent on PPAR has not been investigated. MethodsFirst, using mice lacking adipose tissue lipolysis through adipocyte-specific deletion of adipose triglyceride lipase (ATGL), we characterized the responses dependent on adipocyte ATGL during fasting. Next, we performed liver whole genome expression analysis in fasted mice upon deletion of adipocyte ATGL or hepatocyte PPAR. Finally, we tested the consequences of hepatocyte-specific PPAR deficiency during pharmacological induction of adipocyte lipolysis with a {beta}3-adrenergic receptor agonist. ResultsIn the absence of ATGL in adipocytes, ketone body and FGF21 productions were impaired in response to starvation. Liver transcriptome analysis revealed that adipocyte ATGL is critical for regulation of hepatic gene expression during fasting and highlighted a strong enrichment in PPAR target genes in this condition. Genome expression analysis confirmed that a large set of fasting-induced genes are sensitive to both ATGL and PPAR. Adipose tissue lipolysis induced by acute activation of the {beta}3-adrenergic receptor also triggered PPAR-dependent responses in the liver, supporting a role for adipocyte-derived fatty acids as dominant signals for hepatocyte PPAR activity. In addition, the absence of hepatocyte PPAR altered brown adipose tissue (BAT) morphology and reduced UCP1 expression upon stimulation of the {beta}3-adrenergic receptor. In agreement with this finding, mice lacking hepatocyte PPAR showed decreased tolerance to acute cold exposure. ConclusionsThese results underscore the central role of hepatocyte PPAR in the sensing of adipocyte-derived fatty acids and reveal that its activity is essential for full activation of BAT. Intact PPAR activity in hepatocytes is required for cross-talk between adipose tissues and the liver during fat mobilization during fasting and cold exposure.

physiology↗