Biology subjects

Tsitrina, A.

Publications and source records attributed to Tsitrina, A..

4 recordsLinked to original sources

bioRxiv2026

Time-restricted feeding corrects aggravation of glucose intolerance and circadian disruption induced by weight cycling in obese young mice

Weight cycling (WC), defined as weight gain, loss, and regain, is common in obesity, but its metabolic consequences remain unclear. We tested whether WC-aggravated glucose intolerance in obesity is age-dependent and linked to circadian disruption. Young (7w) and mid-aged (12m) mice underwent a 15-week dietary intervention: Lean and Obese mice fed normal chow (NC) and high-fat diet (HFD) throughout, respectively. WC mice undergone HFD-induced weight gain, NC-induced weight loss, and a second HFD-induced weight regain. Late-onset obese (LO) mice ate HFD only paralleling weight regain of WC. In young, but not mid-aged mice, prior obesity accelerated weight regain upon HFD re-exposure, and aggravated glucose intolerance beyond that observed in Obese mice. This occurred without a worse adipose inflammatory profile. Rather, WC young mice exhibited blunting of light/dark-phase oscillation of feeding and energy metabolism, adipose and hepatic core clock gene oscillation, and increased hepatic expression of clock and gluconeogenic genes during the inactive phase. Restricting food availability to the active phase did not alter final weight regain, but improved glucose tolerance selectively in WC mice, normalized hepatic gluconeogenic and clock-genes expression in both liver and adipose tissue. These findings identify circadian disruption as a modifiable mediator of the adverse metabolic impact of WC in young-adulthood obesity. HighlightsO_LIWeight cycling is common in obesity, but whether it worsens metabolic dysfunction beyond persistent obesity remains unclear. C_LIO_LIWe asked whether weight cycling aggravates glucose intolerance in an age-dependent manner and whether circadian disruption contributes to this effect. C_LIO_LIIn young, but not mid-aged mice, weight cycling accelerated weight regain and worsened glucose intolerance, accompanied by blunted diurnal oscillation of behavioral parameters and core clock gene expression, without exaggerated adipose inflammation. C_LIO_LIActive-phase time-restricted feeding improved WC-induced aggravated glucose tolerance and circadian oscillation, identifying circadian disruption as a modifiable mechanism linking weight cycling adverse metabolic outcomes in young-adulthood obesity. C_LI

biochemistry↗

bioRxiv2025

The Divergent 3D Genome Landscapes of Aging and Neurodegenerative mouse models

Chromatin structure is essential for gene regulation and genome stability, and neurons must preserve their 3D genome organization throughout life. This structure gradually deteriorates with aging and is further disrupted in neurodegenerative diseases. To investigate whether aging and neurodegeneration share early chromatin changes or diverge, we performed Hi-C on cortical neurons from adult, aged, and brain-specific SIRT6-knockout (S6-KO) mice, and compared them to the CK-p25 Alzheimers disease model results stratified by {gamma}H2AX levels. All models showed early features such as weakened interactions between chromosomes in expanded nuclei, A-to-B compartment shifts, and loss of architectural loops. However, aged neurons retained TAD prominence, short-range interactions, and enhancer-promoter loops, while pathological models showed reduced TAD prominence, shorter loops, and disorganized A-B mixing. These changes correlate with increased DNA damage. Our findings suggest that aging represents a "primed" state, where chromatin regulation begins to erode, but further stressors like DNA damage are associated with progression toward neurodegenerative breakdown.

molecular biology↗

bioRxiv2025

Mid-aged mice rapidly normalize dysglycemia but aggravate obesity-induced hypothalamic and microglial changes upon dietary obesity reversal

ObjectiveObesity-induced-dysglycemia and hypothalamic-microgliosis coincide, but whether they remain linked upon obesity reversal, and what is the effect of age, remain unclear. Here we hypothesized that rapid normalization of dysglycemia upon obesity-reversal remains linked to microgliosis resolution, but differs between young and mid-aged mice. MethodsYoung (7w) and mid-aged (1y) mice were fed normal chow (NC) or high-fat diet (HFD,8w), then switched to NC (Rev,2w). ResultsCompared to young mice, NC-fed mid-aged mice were heavier and weight-stable, gained weight with HFD comparably, and lost less weight in Rev. HFD-induced dysglycemia was less severe in mid-aged compared to young mice, but similarly normalized by obesity-reversal. However, whole-hypothalamus RNA sequencing revealed 2,419 differentially expressed genes (DEGs) in mid-aged mice, [~]4-times more than in young mice, and in both age-groups [~]80% of DEGs obesity-induced changes were aggravated in Rev. Furthermore, compared with young mice, middle-aged mice showed greater obesity-induced microglial cyto-morphological changes in the arcuate nucleus (ARC), which associated with increased p-NF{kappa}B-(p-p65) nuclear staining. Only in middle-aged mice obesity-induced microglial changes were aggravated by obesity reversal, with cell volume correlating (Rho({rho})=0.691, p=0.001) with adipose tissue crown-like-structures. ConclusionsIn conclusion, rapid dysglycemia normalization is uncoupled to the resolution of hypothalamic microgliosis, more-so in mid-age.

cell biology↗

bioRxiv2022

Adjuvant effects of multifunctional transcription factor and BCG ‎target YB-1: exogenous YB-1 enhances specific antibody ‎production in vivo and protects mice against lethal E. coli ‎challenge

There is growing interest in the beneficial effects of immune system boosting through the administration of adjuvants, not only in acute infections such as COVID but also in chronic degenerative disorders that are potentially associated with infection. The best-known immunopotentiators are Freunds complete adjuvant (FCA) and its relative Bacille Calmete-Guerin (BCG), both based on Mycobacterium species. The key pathogen-associated molecular patterns (PAMPs) in both FCA and BCG are muramyl dipeptides (MDPs and glucosaminyl-MDP, GMDP). We previously identified the evolutionarily conserved protein Y-box factor YB-1/YBX1 as a primary target for MDP/GMDP. Unlike other host receptors for PAMPs, YB-1 is a diffusible molecule, and we therefore explored whether in vivo administration of YB-1, rather than its PAMP ligands, might enhance the immune response to a bacterial antigen and/or influence survival in the face of bacterial infection. We report that mice receiving YB-1 plus GMDP in vivo mount a significantly increased B cell response versus GMDP alone against a test antigen (Yersinia pestis V antigen), and that YB-1 administration alone significantly promotes survival in the face of lethal bacterial (Escherichia coli) challenge in vivo. Independent confirmation is warranted because recombinant YB-1 and its ligands could hold great promise both as adjuvants and as therapeutics.

immunology↗