Biology subjects

Terrien, J.

Publications and source records attributed to Terrien, J..

8 recordsLinked to original sources

bioRxiv2026

Grey mouse lemurs, Microcebus murinus, are a relevant model to study gut microbiome flexibility in response to diet changes

The gut microbiota is a key player in energy balance, impacting both digestion efficiency and the production of metabolites involved in metabolism. Its composition is highly adaptable, especially in response to diet. Changes in human diet and lifestyle over time - from active, fibre-rich diets to sedentary habits with calorie-dense foods - have likely contributed to the rise in metabolic diseases. Rodent models are widely used to study the links between diet, microbiota and metabolism. However, they have important limitations (e.g. artificial environments, uniform diets and biological differences from humans) which can affect the translation of findings to humans. While mice and humans differ in their microbiota species, they do share some functional similarities. The grey mouse lemur (Microcebus murinus) has been proposed as a promising alternative model. This small primate experiences strong seasonal changes in food availability, leading to distinct physiological states (energy-saving in winter vs active in summer), even in captivity. It is increasingly recognized as a valuable model for biomedical research, supported by recent genomic and molecular advances. However, its gut microbiota has not yet been the subject of study. Consequently, the present study focuses on investigating the gut microbiota of the grey mouse lemur, with a particular emphasis on how these microbiota vary under different dietary regimens. The microbiota of animals fed the standard colony diet was dominated by Prevotella, Bifidobacterium, Megamonas, Streptococcus, Megasphaera and Lactococcus, showing an Prevotella driven enterosignature. We showed that switch from a classical control diet to 3 different diets resulted in change on microbiota composition that is associated with functional redundancy. The present work underline the interest of Microcebus murinus as model for diet and lifestyle studies in relationship with metabolic diseases.

microbiology↗

bioRxiv2025

A primate model organism for cardiac arrhythmias identifies a magnesium transporter in pacemaker function

Cardiac arrhythmias afflict tens of millions of people, causing one-fifth of all deaths1. Although mouse models have aided understanding of some pacemaker genes and arrhythmias2,3, mice are not known to naturally acquire arrhythmias, and the substantial differences between mouse and human cardiac anatomy and physiology have limited their utility in preclinical studies and pharmacological testing2,4. To establish a primate genetic model organism for arrhythmias, we carried out an electrocardiographic (ECG) screen of over 350 lab and wild mouse lemurs (Microcebus spp.), an emerging model organism that is among the smallest, fastest-reproducing, and most abundant primates5. Twenty-two lemurs (6.2%) were identified with eight different naturally-occurring arrhythmias resembling human ECG pathologies (SSS, PACs, Afib, PVCs, NSVT, STD, iTWs, STE). Pedigree construction showed two were familial, premature atrial contractions (PACs)/atrial fibrillation (Afib) and sick sinus syndrome (SSS), an episodic bradycardia. Genome sequencing of the SSS pedigree mapped the disease locus to a 1.4 Mb interval on chromosome 7 and supported autosomal recessive Mendelian inheritance. The most appealing candidate gene in the interval was SLC41A2, a little studied magnesium transporter6,7. SLC41A2 is expressed in human iPSC-derived sinoatrial node cells (iSANC) and localizes to the sarcoplasmic reticulum. Although mouse SLC41A2 knockouts do not show a cardiac pacemaker phenotype8, CRISPR-mediated SLC41A2 knockout altered human iSANC magnesium dynamics and slowed their calcium transient firing rate. The results suggest SLC41A2 functions cell autonomously and primate-specifically in cardiac pacemaker cells, and that intracellular magnesium dynamics have a crucial but previously unappreciated role in setting pacemaker rate. Thus, mouse lemur is a valuable model for discovering new genes, molecules, and mechanisms of the primate pacemaker, and for identifying novel candidate genes and therapeutic targets for human arrhythmias. The approach can be used to elucidate other primate diseases and traits.

genetics↗

bioRxiv2023

Sex-specific central regulation of reproductive activity revealed by the use of deslorelin in the grey mouse lemur, Microcebus murinus.

Deslorelin is a GnRH agonist used in veterinary medicine to temporarily inhibit reproduction in domestic animals and is sometimes tested in captive species in zoo to control population or tame aggressive behaviours in males. However, some studies have revealed the inefficacy of deslorelin specifically in males, contrary to females that follow a classic long-term inhibition of the reproductive hypothalamic-pituitary axis through sexual steroid negative feedback. We implanted 5 males and 6 females grey mouse lemurs (Microcebus murinus), long-day breeders that display a complete inhibition of the reproductive system during winter, at the end of the short-day period, a few weeks before the breeding season. Contrary to females, which exhibited a classic inhibitory response to deslorelin, males testosterone levels increased as well as their testis size, which suggests a sex-specific sensitivity to the negative feedback of sexual steroids before the mating period. We propose that this sex-imbalance is related to the different life-history of males as opposed to females concerning reproductive tasks and behaviour.

physiology↗

bioRxiv2023

Grey Mouse Lemurs' response to acute caloric restriction before reproduction supports the Thrifty Female Hypothesis

The thrifty female hypothesis states that females would preserve more of their energy reserves during winter than males, because of a sex specific time-frame of energy allocation to reproduction. As males reactivate their reproductive axis before the mating period, while females mainly allocate energy in gestation and lactation, we make the hypothesis that males would have to use shorter torpor bouts and longer periods of normothermic activity in order to promote spermatogenesis during winter, a period of low food availability. Here we applied an acute two-week 80%CR in males and females grey mouse lemurs, shortly before the mating period. We show evidence of thriftier phenotypes in wintering females, which performed deeper and longer torpor bouts than males, and ultimately lost less body mass. Our results thus support the thrifty female hypothesis in a seasonally breeding primate, and reinforce the concept of a sex-biased trade-off in using torpor, which might ultimately benefit to reproduction and survival.

evolutionary biology↗

bioRxiv2021

Molecular liver fingerprint reflects the seasonal physiology of the grey mouse lemur (Microcebus murinus) during winter

Grey mouse lemurs (Microcebus murinus) are a primate species exhibiting strong physiological seasonality in response to environmental energetic constraint. They notably store large amounts of lipids during early winter (EW), which are thereafter mobilized during late winter (LW), when food availability is low. In addition, they develop glucose intolerance in LW only. To decipher how the hepatic mechanisms may support such metabolic flexibility, we analyzed the liver proteome of adult captive male mouse lemurs, which seasonal regulations of metabolism and reproduction are comparable to their wild counterparts, during the phases of either constitution or use of fat reserves. We highlight profound changes that reflect fat accretion in EW at the whole-body level, however, without triggering an ectopic storage of fat in the liver. Moreover, molecular regulations would be in line with the lowering of liver glucose utilization in LW, and thus with reduced tolerance to glucose. However, no major regulation was seen in insulin signaling/resistance pathways, which suggests that glucose intolerance does not reach a pathological stage. Finally, fat mobilization in LW appeared possibly linked to reactivation of the reproductive system and enhanced liver detoxification may reflect an anticipation to return to summer levels of food intake. Altogether, these results show that the physiology of mouse lemurs during winter relies on solid molecular foundations in liver processes to adapt fuel partitioning while avoiding reaching a pathological state despite large lipid fluxes. This work emphasizes how the mouse lemur is of primary interest for identifying molecular mechanisms relevant to biomedical field.

molecular biology↗

bioRxiv2021

An organism-wide atlas of hormonal signaling based on the mouse lemur single-cell transcriptome

Hormones mediate long-range cell communication in multicellular organisms and play vital roles in normal physiology, metabolism, and health. Using the newly-completed organism-wide single cell transcriptional atlas of a non-human primate, the mouse lemur (Microcebus murinus), we have systematically identified hormone-producing and -target cells for 84 classes of hormones, and have created a browsable atlas for hormone signaling that reveals previously unreported sites of hormone regulation and species-specific rewiring. Hormone ligands and receptors exhibited cell-type-dependent, stereotypical expression patterns, and their transcriptional profiles faithfully classified the molecular cell type identities, despite their comprising less than 1% of the transcriptome. Cells of similar cell types further display stage, subtype or organ-dependent specification of hormonal signaling, reflecting the precise control of global hormonal regulation. By linking ligand-expressing cells to the cells expressing the corresponding receptor, we constructed an organism-wide map of the hormonal cell communication network. This network was remarkably densely and robustly connected and included a myriad of feedback circuits. Although it includes classical hierarchical circuits (e.g. pituitary [->] peripheral endocrine gland [->] diverse cell types), the hormonal network is overall highly distributed without obvious network hubs or axes. Cross-species comparisons among humans, lemurs, and mice suggest that the mouse lemur better models human hormonal signaling, than does the mouse. Hormonal genes show a higher evolutionary conservation between human and lemur vs. human and mouse at both the genomic level (orthology-mapping and sequence identity) and the transcriptional level (cell type expression patterns). This primate hormone atlas provides a powerful resource to facilitate discovery of regulation on an organism-wide scale and at single-cell resolution, complementing the single-site-focused strategy of classical endocrine studies. The network nature of hormone regulation and the principles discovered here further emphasize the importance of a systems approach to understanding hormone regulation.

genomics↗

bioRxiv2021

Why be thrifty? Sex-specific heterothermic patterns in wintering captive Microcebus murinus do not translate into differences in energy balance.

The physiological mechanisms of the responses toward stressors are the core of ecophysiology studies to understand the limits of an organisms flexibility and better predict the impact of environmental degradation on natural populations. However, little information is available when we question inter-individual variability of these physiological responses, even though they can be particularly important. Some observations of intersexual differences in heterothermy raised the question of a difference in energy management between sexes. Here we assess male and female differences in a mouse lemur model (Microcebus murinus), a highly seasonal Malagasy primate, studying their physiological flexibility toward caloric restriction, and examining the impact on their reproductive success. These animals are adapted for naturally changing food availability and climate conditions, and can express deep torpor, allowing them to spare their energy expenses over the dry and cold season. We monitored body mass and body temperature on 12 males and 12 females over winter, applying a chronic 40% caloric restriction to 6 individuals of each group. Our results showed variability of Tb modulations throughout winter and in response to caloric treatment depending on the sex, as females entered deep torpor regardless of food restriction, while only CR males had a similar response. The use of deep torpor, however, did not translate into better body condition either in females, or in response to CR, and did not clearly affect reproductive success. The favorable captive context potentially buffered the depth of torpor and minimized the positive effects of using torpor on energy savings. However, our results may emphasize the existence of other benefits of heterothermic responses than fat reserves.

physiology↗

bioRxiv2018

Reduced central and peripheral inflammatory responses and increased mitochondrial activity contribute to diet-induced obesity resistance in WSB/EiJ mice.

ObjectivesEnergy balance disruption due to excess of calorie-rich food is considered to be one of the major players in the current worldwide obesity pandemic. In rodents, a high fat diet (HFD) induces not only obesity, but also inflammation and mitochondrial dysfunctions. To identify factors underlying diet-induced obesity (DIO) resistance we compared the wild-derived mouse strain WSB/EiJ, characterized by a striking resistance to DIO, with the more DIO-sensitive C57BL/6J strain.\n\nMethodsWe analysed circulating levels of lipids, cytokines and adipokines as well as hypothalamic markers of inflammatory status and mitochondrial activity in both strains exposed to HFD for three days (3d) or eight weeks (8wk). To identify hypothalamic genes potentially involved in these differential regulations, we selected 86 genes related to inflammation and mitochondrial pathways. We analysed their expression levels by high throughput microfluidic qPCR on RNA extracted from laser micro-dissected arcuate (ARC) and paraventricular (PVN) hypothalamic nuclei of the two strains of mice, under the different HFD treatments.\n\nResultsAfter 3d and 8wk HFD, C57BL/6J mice, in contrast to WSB/EiJ, displayed significantly increased body weight gain, and also increased circulating levels of leptin, cholesterol, HDL and LDL. WSB/EiJ mice displayed a lower inflammatory status, both peripherally (lower levels of circulating cytokines) and centrally (less activated microglia in the hypothalamus) as well as more reactive mitochondria in the hypothalamus. Principal Component Analysis and gene ontology analysis of gene expression data showed, first, that datasets segregated as a function of strain and second, allowed to identify the metabolic pathways involved. These results were reinforced by the identification of strain-specific differential expression of several individual hypothalamic genes as well as differential effects of HFD between strains.\n\nConclusionsAdaptation to metabolic stress in the DIO-resistant WSB/EiJ strain implicates enhanced lipid metabolism, lower peripheral and hypothalamic inflammatory status and higher mitochondrial activity than in the C57BL/6J strain. These results point to the implication of the hypothalamic inflammatory and mitochondrial pathways as key factors in the control of energy homeostasis and the resistance to DIO.\n\nDeclarations of interest: none\n\nHighlightsO_LIDiet-induced-obesity resistance of WSB/EiJ implicates enhanced lipid metabolism\nC_LIO_LIWSB/EiJ mice are protected from HFD-induced peripheral and central inflammation\nC_LIO_LIEnhanced hypothalamic transport and signalling of endocrine molecules in WSB/EiJ\nC_LIO_LIWSB/EiJ hypothalamic mitochondria dynamics differ from C57BL/6J\nC_LIO_LIDifferential regulation of hypothalamic inflammatory/mitochondria genes in WSB/EiJ\nC_LI

physiology↗