Biology subjects

Yuldasheva, N.

Publications and source records attributed to Yuldasheva, N..

4 recordsLinked to original sources

bioRxiv2025

Contribution of endothelial Piezo1 in mechanically induced muscle hypertrophy

Piezo1 proteins form nonselective cation channels with key roles in endothelial responses to mechanical forces. Here we reveal that endothelial Piezo1 regulates skeletal muscle hypertrophy following mechanical overload. Using a conditional endothelial cell-specific deletion of Piezo1 in adult mice, we assessed the role of endothelial Piezo1 in mechanical overload-induced muscle hypertrophy in the extensor digitorum longus. Endothelial Piezo1 deletion blunted muscle hypertrophy following mechanical overload despite normal baseline vascularisation, as evidenced by a lack of increase in muscle mass and abolished myofibre growth. Despite being required for optimal muscle growth, endothelial Piezo1 was dispensable for muscle regeneration after injury. In line with this, the reduced muscle growth following mechanical overload was not associated with impaired myonuclear accretion. We suggest that endothelial Piezo1 participates in a myofibre partnership that regulates skeletal muscle growth in response to mechanical overload.

physiology↗

bioRxiv2021

Paracrine role for endothelial IGF-1 receptor in white adipocyte beiging

There are at least two distinct types of thermogenic adipocyte in mammals: a pre-existing form established during development, termed classical brown adipocytes and an inducible form, beige adipocytes1-3. Various environmental cues can stimulate a process frequently referred to as beiging of white adipose tissue (WAT), leading to enhanced thermogenesis and obesity resistance 4, 5. Whilst beiging of WAT as a therapeutic goal for obesity and obesity-related complications has attracted much attention6-9; therapeutics stimulating beiging without deleterious side-effects remain elusive10. The endothelium lines all blood vessels and is therefore in close proximity to all cells. Many studies support the possibility that the endothelium acts as a paracrine organ11-14. We explored the potential role of endothelial insulin-like growth factor-1 receptor (IGF-1R) as a paracrine modulator of WAT phenotype. Here we show that a reduction in endothelial IGF-1R expression in the presence of nutrient excess leads to white adipocyte beiging, increases whole-body energy expenditure and enhances insulin sensitivity via a non-cell autonomous paracrine mechanism. We demonstrate that this is mediated by endothelial release of malonic acid, which we show, using prodrug analogues, has potentially therapeutically-relevant properties in the treatment of metabolic disease.

cell biology↗

bioRxiv2018

Aged insulin resistant macrophages reveal dysregulated cholesterol biosynthesis, a pro-inflammatory profile and reduced foam cell formation capacity

Insulin resistance is the central defining feature of type 2 diabetes and an independent risk factor for the development of atherosclerosis. In addition, aging is a major risk factor in the development of insulin resistance and cardiovascular disease. Macrophages play a pivotal roles the the developments of diabetes and atherosclerosis and express insulin receptors. Despite their relevance however, the effect of insulin and insulin resistance on macrophages regarding their inflammatory status, foam cell formation capacity and affect on atherosclerosis are unclear. By taking advantage of a mouse model that recapitulates the effects of chronic PI3K pathway hyperstimulation in macrophages through SHIP2 knock-down, we show that insulin resistance in aged macrophages promotes a proinflammatory phenotype while modulating the cholesterol biosynthesis pathway. These altered characteristics may contribute to the development of chronic inflammatory disease frequently observed with age. Moreover, aged insulin-resistant proinflammatory macrophages display an altered response to acute inflammatory stimulus and reduced foam cell formation capacity. Our work also highlights for the first time, the complex and contrasting immunomodulatory effects of insulin on macrophages in aged mice.\n\nSignificanceO_LIFirst study to explore the effects of macrophage insulin resistance in aged cells.\nC_LIO_LIInsulin resistance in aged macrophages results in the reprogramming of the transcriptome with more than 4000 genes being differentially regulated.\nC_LIO_LIInsulin resistance in aged macrophages results in upregulation of IFN signalling pathway, cholesterol biosynthesis pathway and inflammasome gene expression.\nC_LIO_LIInsulin directly regulates macrophage cholesterol biosynthesis, IFN and inflammasome gene expression in a time- and dose-dependent manner.\nC_LIO_LIInsulin resistant aged macrophages exhibit reduced capacity to become foam cells.\nC_LI

immunology↗

bioRxiv2018

Genetic patterning in Central Eurasia: population history and pigmentation

Central-western Asia has often been underrepresented in population genetic studies, but it is important for the clarification of the peopling of Eurasia and the relationship between its western and eastern extremities. We genotyped individuals from over 40 population groups, mostly central Eurasian, for mitochondrial HVR1, CCR5del32 and five functional MC1R variants (p.Val60Leu, p.Val92Met, p.Arg151Cys, p.Arg160Trp, p.Arg163Gln), and collected published genotype data for comparison. Mitochondrial profiles confirm both the higher heterozygosity in Central Asia than in surrounding areas, and the broadly northern European distribution of CCR5del32. The MC1R variants profile alone is a good determinant of the longitudinal position of a population group, and combined FST values divide Eurasia into seven broad geographic divisions. We can conclude that Central Asia shares genetic features with both eastern and western Eurasia, compatible with both a scenario where the former acted as a source for the latter twos genetic diversity, or one where Central Asia is a hybrid zone where eastern and western peoples met. Furthermore, the overall high FST values for functional MC1R variants combined with presumed selection pressures on skin pigmentation in low-UV areas lead us to conclude that different variants were selected for in east and west Eurasia, an example of convergent evolution.

genetics↗