Biology subjects

Yoel, U.

Publications and source records attributed to Yoel, U..

3 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

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↗

bioRxiv2023

Human subcutaneous and visceral adipocyte atlases uncover classical and specialized adipocytes and depot-specific patterns

Human adipose depots are functionally distinct. Yet, recent single-nucleus RNA-sequencing (snRNA-seq) analyses largely uncovered overlapping/similar cell-type landscapes. We hypothesized that adipocytes subtypes, differentiation trajectories, and/or intercellular communication patterns could illuminate this depot similarity-difference gap. For this, we performed snRNA-seq of human subcutaneous and visceral adipose tissue. Whereas the majority of adipocytes in both depots were classical, namely enriched in lipid metabolism pathways, we also observed specialized adipocyte subtypes that were enriched in immune-related, extracellular matrix deposition (fibrosis), vascularization/angiogenesis, or ribosomal processes. Pseudo-temporal analysis suggested a developmental trajectory from adipose progenitor cells to classical adipocytes via specialized adipocytes, suggesting that the classical state stems from loss, rather than gain, of specialized functions. Lastly, intercellular communication routes were consistent with the different inflammatory tone of the two depots. Jointly, these findings provide a high-resolution view into the contribution of cellular composition, differentiation, and intercellular communication patterns to human fat depot differences.

systems biology↗