Biology subjects

Almendros, I.

Publications and source records attributed to Almendros, I..

3 recordsLinked to original sources

bioRxiv2025

Intermittent Hypoxia Drives Early Metabolic Dysfunction in Brown Adipose Tissue

BackgroundObstructive sleep apnea (OSA) is associated with metabolic dysfunction, yet the early impact of intermittent hypoxia (IH)--a defining feature of OSA--on brown adipose tissue (BAT) remains unclear. MethodsWe investigated the direct and early effects of IH on BAT using both in vitro and in vivo approaches. Differentiated mouse brown adipocytes were exposed to IH for 48 hours and analyzed for {beta}3-adrenergic signaling, lipolysis, and thermogenic activation. Complementary in vivo studies assessed transcriptomic, morphological, and functional changes in BAT, white adipose tissue (WAT), and liver after 1 or 4 weeks of IH exposure in mice. ResultsIH blunted {beta}3-adrenergic signaling in cultured brown adipocytes, leading to reduced phosphorylation of key signaling proteins, impaired lipolytic response, and decreased expression of UCP1. In vivo, BAT exhibited early and sustained transcriptomic rewiring characterized by downregulation of pathways related to fatty acid metabolism, oxidative phosphorylation, and peroxisomal function. These molecular changes were accompanied by abnormal lipid droplet enlargement and a reduced lipolytic response to adrenergic stimulation. In contrast, WAT showed transient gene expression changes, and the liver displayed a delayed and robust transcriptomic response evident only after four weeks of IH exposure. Despite these metabolic alterations, thermogenic responses to cold challenge remained intact in IH-treated mice. ConclusionsBAT is uniquely and rapidly affected by intermittent hypoxia, undergoing functional, molecular, and morphological changes within one week of exposure. These alterations precede systemic inflammation and metabolic dysfunction, positioning BAT dysfunction as an early event in the pathogenesis of OSA-associated metabolic disease.

pathology↗

bioRxiv2021

The force loading rate drives cell mechanosensing through both reinforcement and fluidization

Cell response to force regulates essential processes in health and disease. However, the fundamental mechanical variables that cells sense and respond to remain unclear. Here we show that the rate of force application (loading rate) drives mechanosensing, as predicted by a molecular clutch model. By applying dynamic force regimes to cells through substrate stretching, optical tweezers, and atomic force microscopy, we find that increasing loading rates trigger talin-dependent mechanosensing, leading to adhesion growth and reinforcement, and YAP nuclear localization. However, above a given threshold the actin cytoskeleton undergoes fluidization and softens, decreasing loading rates and preventing reinforcement. By stretching rat lungs in vivo, we show that a similar phenomenon occurs at the organ level. Our results show that cell sensing of external forces and of passive mechanical parameters (like tissue stiffness) can be understood through the same mechanisms, driven by the properties under force of the mechanosensing molecules involved.

biophysics↗

bioRxiv2020

Impact of sleep fragmentation, heart failure, and their combination, on the gut microbiome

Heart failure (HF) is a common condition associated with a high rate of hospitalizations and adverse outcomes. HF is characterized by impairments of the cardiac ventricular filling and/or ejection of blood capacity. Sleep fragmentation (SF) involves a series of short sleep interruptions that lead to fatigue and contribute to cognitive impairments and dementia. Both conditions are known to be associated with increased inflammation and dysbiosis of the gut microbiota. In the present study, male mice were distributed into four groups, and subjected for four weeks to either HF, SF, both HF and SF, or left unperturbed as controls. We used 16S metabarcoding to assess fecal microbiome composition before and after the experiments. Evidence for distinct alterations in several bacterial groups and an overall decrease in alpha diversity emerged in HF and SF treatment groups. Combined HF and SF conditions, however, showed no synergism, and observed changes were not always additive, suggesting that some of the individual effects of either HF or SF cancel each other out when applied concomitantly. IMPORTANCEThe study demonstrates the potential of the gut microbiome as a source of molecular markers for the diagnosis, prevention, and treatment of both heart failure and sleep fragmentation conditions in isolation. Our results provide the first evidence of an antagonistic effect of the presence of both conditions in the gut microbiome dysbiosis, showing an attenuation of the alterations that are observed when considering them separately.

microbiology↗