Biology subjects

Kurgan, N.

Publications and source records attributed to Kurgan, N..

4 recordsLinked to original sources

bioRxiv2025

The metabolic and molecular mechanisms underlying running-induced energy compensation

Exercise not only regulates energy expenditure but also appetite, yet the underpinnings remain unclear. We describe that increased energy intake is a defense against energy loss that depends on initial running distance and operates independently of diet and age. Running caused a rapid circadian-dependent fat remodeling leading to a decline in circulating leptin accompanied by the activation of hypothalamic neurons. We discovered that the activation of the {beta}3-adrenergic receptor drives running-induced fat loss and the lower leptin triggers energy compensation by upregulating Neuropeptide Y. Once energy compensation is achieved, running is associated with molecular changes in hypothalamic signaling related to appetite and functional adaptations, such as enhanced sensitivity to hunger and satiety signals and increased responsiveness to appetite suppression induced by -Melanocyte-Stimulating Hormone. The increased food intake persisted without fat rebound beyond running in both lean and obese young mice, uncovering a new homeostatic balance in young mice.

physiology↗

bioRxiv2025

Body Fluid Proteomic Landscape of Acute Exercise

Physical activity improves health, yet the molecular mechanisms remain partially understood. This study presents a high-resolution, time-resolved atlas profiling 10,127 proteins across plasma, saliva, and urine from healthy adults post-acute exercise. Exercise regulated over 3,000 proteins, revealing distinct, fluid-specific temporal dynamics. By integrating fluid-specific exercise signatures with tissue and disease atlases, we delineated the contribution of tissues and associations to various diseases. Network analysis across body fluids elucidated coordinated remodeling in the extracellular matrix and immune activation orchestrating exercise-induced networks. Many exercise-responsive plasma proteins were robust across age, sex, and exercise modalities, indicating a conserved systemic signature. Integration with genetic data established exercise-regulated proteins as modulators of metabolic traits and identified over 200 targeted by approved drugs, highlighting their impact on disease-relevant pathways. This comprehensive atlas, available as an open-access resource https://cbmr.ku.dk/research/research-groups/deshmukh-group/shiny-apps/, advances our molecular insight into exercise adaptations and enables exerkine discovery, biomarker development, and pharmacological exercise-mimetic strategies. O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=200 SRC="FIGDIR/small/656705v1_ufig1.gif" ALT="Figure 1"> View larger version (47K): org.highwire.dtl.DTLVardef@bf3baforg.highwire.dtl.DTLVardef@e79b11org.highwire.dtl.DTLVardef@1757b9borg.highwire.dtl.DTLVardef@5fddc_HPS_FORMAT_FIGEXP M_FIG C_FIG HighlightsO_LIExercise induces robust and distinct changes across body fluid proteomes C_LIO_LITissue remodeling and immune activation drive exercise-induced network expansion C_LIO_LI[~]1,000 exercise-regulated plasma proteins are age, exercise mode, or sex-specific C_LIO_LIGenetic inference identifies druggable exerkines that regulate health and disease C_LI

physiology↗

bioRxiv2022

Sclerostin influences exercise-induced adaptations in body composition and white adipose tissue morphology in male mice

Sclerostin is an inhibitor of the osteogenic Wnt/{beta}-catenin signalling pathway that has an endocrine role in regulating adipocyte differentiation and metabolism. Additionally, subcutaneous white adipose tissue (scWAT) sclerostin content decreases following exercise training (EXT). Therefore, we hypothesized that EXT-induced reductions in adipose tissue sclerostin may play a role in regulating adaptations in body composition and whole-body metabolism. To test this hypothesis, 10-week-old male C57BL/6J mice were either sedentary (SED) or performing 1h of treadmill running at [~]65-70% VO2max 5 d/week (EXT) for 4 weeks and had subcutaneous (s.c) injections of either saline (C) or recombinant sclerostin (S) (0.1 mg/kg body mass) 5 d/week; thus, making 4 groups (SED-C, EXT-C, SED-S, and EXT-S; n=12/group). No differences in body mass were observed between experimental groups, while food intake was higher in EXT (p=0.03) and S (p=0.08) groups. There was a higher resting energy expenditure in all groups compared to SED-C. EXT-C had a higher lean mass and lower fat mass percentage compared to SED-C and SED-S. No differences in body composition were observed in either the SED-S or EXT-S groups. Lower scWAT (inguinal), vWAT (epididymal) mass, and scWAT adipocyte cell size and increased percentage of multilocular cells in scWAT were observed in the EXT-C group compared to SED-C, while lower vWAT was only observed in the EXT-S group. EXT mice had increased iWAT Lrp4 and mitochondrial content and sclerostin treatment only inhibited increased Lrp4 content with EXT. Together, these results provide evidence that reductions in resting sclerostin with exercise training may influence associated alterations in energy metabolism and body composition, particularly in scWAT.

physiology↗

bioRxiv2022

Kynurenine metabolism is altered in mdx mice: a potential muscle to brain connection

Regular exercise can direct muscle kynurenine (KYN) metabolism toward the neuroprotective branch of the kynurenine pathway thereby limiting the accumulation of neurotoxic metabolites in the brain and contributing to mental resilience. While the effect of regular exercise has been studied, the effect of muscle disease on KYN metabolism has not yet been investigated. Previous work has highlighted anxiety-like behaviors in approximately 25% of patients with DMD, possibly due to altered KYN metabolism. Here, we characterized KYN metabolism in mdx mouse models of Duchenne muscular dystrophy (DMD). Young (8-10 week old) DBA/2J (D2) mdx mice, but not age-matched C57BL/10 (C57) mdx mice, had lower levels of circulating KYNA and KYNA:KYN ratio compared with their respective wild-type (WT) controls. Moreover, only D2 mdx mice displayed signs of anxiety-like behaviour, spending more time in the corners of their cages during a novel object recognition test when compared with WT. Along with this, we found that muscles from D2 mdx mice had less peroxisome proliferator-activated receptor-gamma coactivator 1-alpha and kynurenine amino transferase-1 enzyme content as well as elevated expression of inflammatory cytokines compared with WT muscles. Thus, our pilot work shows that KYN metabolism is altered in D2 mdx mice, with a potential contribution from altered muscle health.

physiology↗