Serum proteomic profiling of physical activity reveals CD300LG as a novel exerkine with a potential causal link to glucose homeostasis DOI Creative Commons
Sindre Lee-Ødegård, Marit Hjorth, Thomas Olsén

et al.

eLife, Journal Year: 2024, Volume and Issue: 13

Published: April 5, 2024

Physical activity has been associated with preventing the development of type 2 diabetes and atherosclerotic cardiovascular disease. However, our understanding precise molecular mechanisms underlying these effects remains incomplete good biomarkers to objectively assess physical are lacking. We analyzed 3072 serum proteins in 26 men, normal weight or overweight, undergoing 12 weeks a combined strength endurance exercise intervention. estimated insulin sensitivity hyperinsulinemic euglycemic clamp, maximum oxygen uptake, muscle strength, used MRI/MRS evaluate body composition organ fat depots. Muscle subcutaneous adipose tissue biopsies were for mRNA sequencing. Additional association analyses performed samples from up 47,747 individuals UK Biobank, as well using two-sample Mendelian randomization mice models. Following intervention, we observed significant changes 283 proteins. Notably, 66 elevated overweight men positively liver before regimen, but normalized after exercise. Furthermore, 19.7 12.1% exercise-responsive proteins, corresponding expression levels fat, respectively, shown. The protein CD300LG displayed consistent alterations blood, muscle, fat. Serum exhibited positive associations sensitivity, angiogenesis-related gene both was negatively glucose Biobank. In this sample, between significantly stronger than women. analysis suggested potential causal relationships fasting glucose, hr an oral tolerance test, HbA1c. Additionally, Cd300lg responded mouse model, signs impaired male, not female, knockout mice. Our study identified several novel whose change response prolonged composition, homeostasis. increased is link improved levels. may be promising biomarker therapeutic target diabetes. South-Eastern Norway Regional Health Authority, Simon Fougners Fund, Diabetesforbundet, Johan Selmer Kvanes' legat til forskning og bekjempelse av sukkersyke. Biobank resource reference 53641. Australian National Medical Research Council Investigator Grant (APP2017942). Discovery Early Career Award (DE220101226). (Project grant: 325640 Mobility 287198). Student Program at University Oslo. Novo Nordisk Fonden Excellence Emerging Endocrinology Metabolism 2023 (NNF23OC0082123). clinicaltrials.gov: NCT01803568.

Language: Английский

Machine learning and single-cell analysis uncover distinctive characteristics of CD300LG within the TNBC immune microenvironment: experimental validation DOI Creative Commons

Baoxi Zhu,

Hong Wan,

Zichen Ling

et al.

Clinical and Experimental Medicine, Journal Year: 2025, Volume and Issue: 25(1)

Published: May 17, 2025

Investigating the essential function of CD300LG within tumor microenvironment in triple-negative breast cancer (TNBC). Transcriptomic and single-cell data from TNBC were systematically collected integrated. Four machine learning algorithms employed to identify distinct target genes patients. Specifically, CIBERSORT ssGSEA utilized elucidate immune infiltration patterns, whereas TIDE TCGA predicted immune-related outcomes. Moreover, sequencing analyzed investigate CD300LG-positive cells microenvironment. Finally, immunofluorescence staining confirmed significance phenotyping. After screening independent dataset validation, was identified as a unique prognostic biomarker for cancer. Enrichment analysis revealed that expression is strongly linked inflammation-related pathways, especially those associated with cell cycle. The presence CD8+ T M1-type macrophages elevated higher group, abundance M2-type macrophage showed significant decrease. Immunotherapy prediction models indicated individuals low exhibited better responses PD-1 therapy. Additionally, RNA analyses uncovered robust association between involved invasion. plays pivotal role represents promising therapeutic target.

Language: Английский

Citations

0
Serum proteomic profiling of physical activity reveals CD300LG as a novel exerkine with a potential causal link to glucose homeostasis DOI Creative Commons
Sindre Lee-Ødegård, Marit Hjorth, Thomas Olsén

et al.

eLife, Journal Year: 2024, Volume and Issue: 13

Published: April 5, 2024

Physical activity has been associated with preventing the development of type 2 diabetes and atherosclerotic cardiovascular disease. However, our understanding precise molecular mechanisms underlying these effects remains incomplete good biomarkers to objectively assess physical are lacking. We analyzed 3072 serum proteins in 26 men, normal weight or overweight, undergoing 12 weeks a combined strength endurance exercise intervention. estimated insulin sensitivity hyperinsulinemic euglycemic clamp, maximum oxygen uptake, muscle strength, used MRI/MRS evaluate body composition organ fat depots. Muscle subcutaneous adipose tissue biopsies were for mRNA sequencing. Additional association analyses performed samples from up 47,747 individuals UK Biobank, as well using two-sample Mendelian randomization mice models. Following intervention, we observed significant changes 283 proteins. Notably, 66 elevated overweight men positively liver before regimen, but normalized after exercise. Furthermore, 19.7 12.1% exercise-responsive proteins, corresponding expression levels fat, respectively, shown. The protein CD300LG displayed consistent alterations blood, muscle, fat. Serum exhibited positive associations sensitivity, angiogenesis-related gene both was negatively glucose Biobank. In this sample, between significantly stronger than women. analysis suggested potential causal relationships fasting glucose, hr an oral tolerance test, HbA1c. Additionally, Cd300lg responded mouse model, signs impaired male, not female, knockout mice. Our study identified several novel whose change response prolonged composition, homeostasis. increased is link improved levels. may be promising biomarker therapeutic target diabetes. South-Eastern Norway Regional Health Authority, Simon Fougners Fund, Diabetesforbundet, Johan Selmer Kvanes' legat til forskning og bekjempelse av sukkersyke. Biobank resource reference 53641. Australian National Medical Research Council Investigator Grant (APP2017942). Discovery Early Career Award (DE220101226). (Project grant: 325640 Mobility 287198). Student Program at University Oslo. Novo Nordisk Fonden Excellence Emerging Endocrinology Metabolism 2023 (NNF23OC0082123). clinicaltrials.gov: NCT01803568.

Language: Английский

Citations

2