Authors: Lee-Odegard, S.; Hjorth, M.; Olsen, T.; Moen, G.-H.; Daubney, E.; Evans, D. M.; Hevener, A. L.; Lusis, A. J.; Zhou, M.; Seldin, M. M.; Allayee, H.; Viken, J. K.; Gulseth, H.; Norheim, F.; Drevon, C. A.; Birkeland, K. I.

Score: 1.2, Published: 2024-02-12

DOI: 10.1101/2024.02.10.24302626

BackgroundPhysical activity has been associated with preventing the development of type 2 diabetes and atherosclerotic cardiovascular disease. However, our understanding of the precise molecular mechanisms underlying these effects remains incomplete and good biomarkers to objectively assess physical activity are lacking. MethodsWe analyzed 3072 serum proteins in 26 men, normal weight or overweight, undergoing 12 weeks of a combined strength and endurance exercise intervention. We estimated insulin sensitivity with hyperinsulinemic euglycemic clamp, maximum oxygen uptake, muscle strength, and used MRI/MRS to evaluate body composition and organ fat depots. Muscle and subcutaneous adipose tissue biopsies were used for mRNA sequencing. Additional association analyses were performed in samples from up to 47,747 individuals in the UK Biobank, as well as using 2-sample Mendelian randomization and mice models. ResultsFollowing 12 weeks of exercise intervention, we observed significant changes in 283 serum proteins. Notably, 66 of these proteins were elevated in overweight men and positively associated with liver fat before the exercise regimen, but were normalized after exercise. Furthermore, for 19.7% and 12.1% of the exercise-responsive proteins, corresponding changes in mRNA expression levels in muscle and fat, respectively, were shown. The protein CD300LG displayed consistent alterations in blood, muscle, and fat. Serum CD300LG exhibited positive associations with insulin sensitivity, and to angiogenesis-related gene expression in both muscle and fat. Furthermore, serum CD300LG was positively associated with physical activity and negatively associated with glucose levels in the UK Biobank. In this sample, the association between serum CD300LG and physical activity was significantly stronger in men than in women. Mendelian randomization analysis suggested potential causal relationships between levels of serum CD300LG and fasting glucose, 2-hour glucose after an oral glucose tolerance test, and HbA1c. Additionally, Cd300lg responded to exercise in a mouse model, and we observed signs of impaired glucose tolerance in male, but not female, Cd300lg knockout mice. ConclusionOur study identified several novel proteins in serum whose levels change in response to prolonged exercise and were significantly associated with body composition, liver fat, and glucose homeostasis. Serum CD300LG increased with physical activity and is a potential causal link to improved glucose levels. CD300LG may be a promising exercise biomarker and a therapeutic target in type 2 diabetes.

Authors: Perry, A. S.; Hadad, N.; Chatterjee, E.; Jimenez Ramos, M.; Farber-Eger, E.; Roshani, R.; Stolze, L.; Zhao, S.; Martens, L.; Kendall, T.; Thone, T.; Amancherla, K.; Bailin, S.; Gabriel, C.; Koethe, J.; Carr, J. J.; Terry, J. G.; Freedman, J.; Tanriverdi, K.; Alsop, E.; Van Keuren-Jensen, K.; Sauld, J.; Mahajan, G.; Khan, S.; Colangelo, L.; Nayor, M.; Fisher-Hoch, S.; McCormick, J.; North, K.; Below, J.; Wells, Q.; Abel, D.; Kalhan, R.; Scott, C.; Guilliams, M.; Fallowfield, J.; Banovich, N.; Das, S.; Shah, R.

Score: 3.6, Published: 2024-01-29

DOI: 10.1101/2024.01.26.24301828

Metabolic dysfunction-associated steatotic liver disease (MASLD) prevalence is increasing in parallel with an obesity pandemic, calling for novel strategies for prevention and treatment. We defined a circulating proteome of human MASLD across {approx}7000 proteins in {approx}5000 individuals from diverse, at-risk populations across the metabolic health spectrum, demonstrating reproducible diagnostic performance and specifying both known and novel metabolic pathways relevant to MASLD (central carbon and amino acid metabolism, hepatocyte regeneration, inflammation, fibrosis, insulin sensitivity). A parsimonious proteomic signature of MASLD was associated with a protection from MASLD and its related multi-system metabolic consequences in >26000 free-living individuals, with an additive effect to polygenic risk. The MASLD proteome was encoded by genes that demonstrated transcriptional enrichment in liver, with spatial transcriptional activity in areas of steatosis in human liver biopsy and dynamicity for select targets in human liver across stages of steatosis. We replicated several top relations from proteomics and spatial tissue transcriptomics in a humanized "liver-on-a-chip" model of MASLD, highlighting the power of a full translational approach to discovery in MASLD. Collectively, these results underscore utility of blood-based proteomics as a dynamic "liquid biopsy" of human liver relevant to clinical biomarker and mechanistic applications.

Authors: Yan, Z.; Liu, M.; Wu, x.; Xiong, J.; Yang, Z.; Zhang, N.; Yang, X.; Liu, M.

Score: 0.8, Published: 2024-02-16

DOI: 10.1101/2024.02.14.24302641

ABSTRACT Objectives Establish clinical evidence regarding acupuncture combined with statin for blood lipid control in patients with angina pectoris (AP) of coronary heart disease (CHD) by systematically analyzing data from all available studies. Design A systematic review and meta-analysis. Data sources The literature search involved eight databases (China National Knowledge Infrastructure, Chinese Biomedical Literature Database, Wanfang, VIP Database for Chinese Technical Periodicals, PubMed, Embase, Web of Science, and Cochrane Library) and was finished on February 1, 2024. Eligibility criteria Random controlled trials (RCTs) investigating the efficacy of acupuncture combined with statin on lipid levels in patients with AP of CHD were eligible. The outcomes assessed were the lipid metabolism indicators, including TC, TG, LDL-C, and HDL-C, as well as the safety of the treatment. Data extraction and synthesis Data extraction and quality evaluation were conducted by two independent reviewers, with any discrepancies discussed by a third researcher. Pooled mean differences (MD) with 95% confidence intervals (CIs) were calculated for each outcome. Sensitivity and subgroup analyses were carried out to explore the heterogeneity. Publication bias was assessed using a funnel plot. The quality of the evidence was evaluated using the GRADE system. Results The final meta-analysis included nine eligible studies involving 754 patients. When comparing statin group, the acupuncture plus statin group showed lower levels of TC (MD: -0.48, -0.61 to -0.35, p-value less than 0.00001), TG (MD: -0.59, -0.86 to -0.32, p-value less than 0.00001), LDL-C (MD: -0.66, -0.99 to -0.33, p-value equal to 0.0001), and higher levels of HDL-C (MD: 0.16, 0.06 to 0.26, p-value equal to 0.001). Each study included in the analysis exhibited some degree of bias. Significant publication bias was detected for the primary outcomes. Evidence quality for the primary outcomes was graded as very low. Conclusions: Acupuncture as an adjunctive treatment can further improve lipid profile in individuals diagnosed with AP of CHD based on statin therapy. However, the clinical significance of this effect remains unclear; it is necessary to confirm the findings through more high-quality RCTs in the future. Trial registration number PROSPERO CRD42023465292. Keywords: Acupuncture, Statin, Angina pectoris, Lipid profiles, Meta-analysis.