Gene expression is differentially regulated in skeletal muscle and circulating immune cells in response to an acute bout of high-load strength exercise

BACKGROUND: High-intensity exercise induces many metabolic responses. In is unknown whether the response in the peripheral blood mononuclear cells (PBMCs) reflects the response in skeletal muscle and whether mRNA expression after exercise can be modulated by nutritional intake. The aims were to (i) investigate the effect of dairy proteins on acute responses to exercise in skeletal muscle and PBMCs measuring gene expression and (ii) compare this response in young and older subjects. METHODS: We performed two separate studies in young (20–40 years) and older subjects (≥70 years). Subjects were randomly allocated to a milk group or a whey group. Supplements were provided immediately after a standardized exercise session. We measured mRNA expression of selected genes after a standardized breakfast and 60/120 min after finishing the exercise, using RT-qPCR. RESULTS: We observed no significant differences in mRNA expression between the milk and the whey group; thus, we merged both groups for further analysis. The mRNA expression of IL6, TNF, and CCL2 in skeletal muscle increased significantly after exercise compared with smaller or no increase, in mRNA expression in PBMCs in all participants. The mRNA expression of IL1RN, IL8, and IL10 increased significantly in skeletal muscle and PBMCs. Some mRNA transcripts were differently regulated in older compared to younger participants in PBMCs. CONCLUSIONS: An acute bout of heavy-load strength exercise, followed by protein supplementation, caused overlapping, but also unique, responses in skeletal muscle and PBMCs, suggesting tissue-specific functions in response to exercise. However, no different effects of the different protein supplements were observed. Altered mRNA expressions in PBMCs of older participants may affect regenerative mechanisms

Increased protein intake affects pro-opiomelanocortin (POMC) processing, immune function and IGF signaling in peripheral blood mononuclear cells of home-dwelling old subjects using a genome-wide gene expression approach

Background Adequate protein intake among older adults is associated with better health outcomes such as immune function and metabolic regulation of skeletal muscle, but conflicting results make it difficult to define the optimal intake. To further understand the impact of protein intake on metabolic processes, the aim of the study was to explore genome-wide gene expression changes in peripheral blood mononuclear cells (PBMCs) in home-dwelling old subjects after increased protein intake for 12 weeks. Method In a parallel double-blind randomized controlled intervention study, subjects (≥ 70 years) received a protein-enriched milk (2 × 20 g protein/day, n = 14, mean (±SD) age 76.9 ± 4.9 years) or an isocaloric carbohydrate drink (n = 17, mean (±SD) age 77.7 ± 4.8 years) for breakfast and evening meal for 12 weeks. PBMCs were isolated before and after the intervention. Microarray analysis was performed using Illumina technology. Serum levels of gut peptides and insulin growth factor (IGF)-1 were also measured. Results In total 758 gene transcripts were regulated after increased protein intake, and 649 gene transcripts were regulated after intake of carbohydrates (p < 0.05). Forty-two of these genes were overlapping. After adjusting for multiple testing, 27 of the 758 gene transcripts were regulated (FDR, q-value < 0.25) after protein intake. Of these 25 were upregulated and two downregulated. In particular, genes and signaling pathways involved in pro-opiomelanocortin (POMC) processing, immune function, and IGF signaling were significantly altered. Conclusions PBMCs can be used to study gene expression changes after long-term protein intake, as many signaling pathways were regulated after increased protein intake. The functional significance of these findings needs to be further investigated. Trial registration ClinicalTrials.gov, ID no. NCT02218333. The study was registered on August 18, 2014

Intake of Fermented Dairy Products Induces a Less Pro‐Inflammatory Postprandial Peripheral Blood Mononuclear Cell Gene Expression Response than Non‐Fermented Dairy Products: A Randomized Controlled Cross‐Over Trial

Scope - It is aimed to investigate how intake of high‐fat meals composed of different dairy products with a similar fat content affects postprandial peripheral blood mononuclear cell (PBMC) expression of inflammation‐related genes, as well as circulating inflammatory markers and metabolites. Methods and results - Healthy subjects (n = 47) consume four different high‐fat meals composed of either butter, cheese, whipped cream, or sour cream in a randomized controlled cross‐over study. Fasting and postprandial PBMC gene expression, plasma metabolites, and circulating inflammatory markers are measured. Using a linear mixed model, it is found that expression of genes related to lymphocyte activation, cytokine signaling, chemokine signaling, and cell adhesion is differentially altered between the four meals. In general, intake of the fermented products cheese and sour cream reduces, while intake of the non‐fermented products butter and whipped cream increases, expression of these genes. Plasma amino acid concentrations increase after intake of cheese compared to the other meals, and the amino acid changes correlate with several of the differentially altered genes. Conclusion - Intake of fermented dairy products, especially cheese, induces a less inflammatory postprandial PBMC gene expression response than non‐fermented dairy products. These findings may partly explain inconsistent findings in studies on health effects of dairy products

Increased protein intake affects pro-opiomelanocortin (POMC) processing, immune function and IGF signaling in peripheral blood mononuclear cells of home-dwelling old subjects using a genome-wide gene expression approach

Abstract Background: Adequate protein intake among older adults is associated with better health outcomes such as immune function and metabolic regulation of skeletal muscle, but conflicting results make it difficult to define the optimal intake. To further understand the impact of protein intake on metabolic processes, the aim of the study was to explore genome-wide gene expression changes in peripheral blood mononuclear cells (PBMCs) in home-dwelling old subjects after increased protein intake for 12 weeks. Method: In a parallel double-blind randomized controlled intervention study, subjects (≥ 70 years) received a protein-enriched milk (2 × 20 g protein/day, n = 14, mean (±SD) age 76.9 ± 4.9 years) or an isocaloric carbohydrate drink (n = 17, mean (±SD) age 77.7 ± 4.8 years) for breakfast and evening meal for 12 weeks. PBMCs were isolated before and after the intervention. Microarray analysis was performed using Illumina technology. Serum levels of gut peptides and insulin growth factor (IGF)-1 were also measured. Results: In total 758 gene transcripts were regulated after increased protein intake, and 649 gene transcripts were regulated after intake of carbohydrates (p &lt; 0.05). Forty-two of these genes were overlapping. After adjusting for multiple testing, 27 of the 758 gene transcripts were regulated (FDR, q-value &lt; 0.25) after protein intake. Of these 25 were upregulated and two downregulated. In particular, genes and signaling pathways involved in pro-opiomelanocortin (POMC) processing, immune function, and IGF signaling were significantly altered. Conclusions: PBMCs can be used to study gene expression changes after long-term protein intake, as many signaling pathways were regulated after increased protein intake. The functional significance of these findings needs to be further investigated

Meals with similar fat content from different dairy products induce different postprandial triglyceride responses in healthy adults:a randomized controlled cross-over trial

Abstract Background: Postprandial lipemia is a risk factor for cardiovascular disease. Dairy products differ in nutrient content and food matrix, and little is known about how different dairy products affect postprandial triglyceride (TG) concentrations. Objective: We investigated the effect of meals with similar amounts of fat from different dairy products on postprandial TG concentrations over 6 h in healthy adults. Methods: A randomized controlled cross-over study was performed on 47 subjects (30% men), with median (25th–75th percentile) age of 32 (25–46) y and body mass index of 23.6 (21.0–25.8) kg/m². Meals included 1 of butter, cheese, whipped cream, or sour cream, corresponding to 45 g of fat (approximately 60 energy%). Serum concentrations of TGs (primary outcome), and total cholesterol (TC), low density lipoprotein cholesterol (LDL cholesterol), high density lipoprotein cholesterol (HDL cholesterol), insulin, glucose, non-esterified fatty acids, and plasma glucose-dependent insulinotropic polypeptide (secondary outcomes) were measured before the meal and 2, 4, and 6 h postprandially. Incremental AUC (iAUC) was calculated for the responses, and data were analyzed using a linear mixed model. Results: Sour cream induced a 61% larger TG-iAUC0–6 h compared to whipped cream (P &lt; 0.001), a 53% larger TG-iAUC0–6 h compared to butter (P &lt; 0.001), and a 23% larger TG-iAUC0–6 h compared to cheese (P = 0.05). No differences in TG-iAUC0–6 h between the other meals were observed. Intake of sour cream induced a larger HDL cholesterol-iAUC0–6 h compared to cheese (P = 0.01). Intake of cheese induced a 124% larger insulin iAUC0–6 h compared to butter (P = 0.006). No other meal effects were observed. Conclusions: High-fat meals containing similar amount of fat from different dairy products induce different postprandial effects on serum TGs, HDL cholesterol, and insulin in healthy adults. The potential mechanisms and clinical impact of our findings remain to be further elucidated. The study was registered at www.clinicaltrials.gov as NCT02836106