In spite of amazing progress in food supply and nutritional science, and a striking increase in life expectancy of approximately 2.5 months per year in many countries during the previous 150 years, modern nutritional research has a great potential of still contributing to improved health for future generations, granted that the revolutions in molecular and systems technologies are applied to nutritional questions. Descriptive and mechanistic studies using state of the art epidemiology, food intake registration, genomics with single nucleotide polymorphisms (SNPs) and epigenomics, transcriptomics, proteomics, metabolomics, advanced biostatistics, imaging, calorimetry, cell biology, challenge tests (meals, exercise, etc.), and integration of all data by systems biology, will provide insight on a much higher level than today in a field we may name molecular nutrition research. To take advantage of all the new technologies scientists should develop international collaboration and gather data in large open access databases like the suggested Nutritional Phenotype database (dbNP). This collaboration will promote standardization of procedures (SOP), and provide a possibility to use collected data in future research projects. The ultimate goals of future nutritional research are to understand the detailed mechanisms of action for how nutrients/foods interact with the body and thereby enhance health and treat diet-related diseases.

Remodeling of extracellular matrix (ECM), including regulation of proteoglycans in skeletal muscle can be important for physiological adaptation to exercise. To investigate the effects of acute and long‐term exercise on the expression of ECM‐related genes and proteoglycans in particular, 26 middle‐aged, sedentary men underwent a 12 weeks supervised endurance and strength training intervention and two acute, 45 min bicycle tests (70% VO₂max), one at baseline and one after 12 weeks of training. Total gene expression in biopsies from m. vastus lateralis was measured with deep mRNA sequencing. After 45 min of bicycling approximately 550 gene transcripts were >50% upregulated. Of these, 28 genes (5%) were directly related to ECM. In response to long‐term exercise of 12 weeks 289 genes exhibited enhanced expression (>50%) and 20% of them were ECM related. Further analyses of proteoglycan mRNA expression revealed that more than half of the proteoglycans expressed in muscle were significantly enhanced after 12 weeks intervention. The proteoglycan serglycin (SRGN) has not been studied in skeletal muscle and was one of few proteoglycans that showed increased expression after acute (2.2‐fold, P < 0.001) as well as long‐term exercise (1.4‐fold, P < 0.001). Cultured, primary human skeletal muscle cells expressed and secreted SRGN. When the expression of SRGN was knocked down, the expression and secretion of serpin E1 (SERPINE1) increased. In conclusion, acute and especially long‐term exercise promotes enhanced expression of several ECM components and proteoglycans. SRGN is a novel exercise‐regulated proteoglycan in skeletal muscle with a potential role in exercise adaptation.

Extracellular vesicles induced by exercise have emerged as potential mediators of tissue crosstalk. Extracellular vesicles and their cargo miRNAs have been linked to dysglycemia and obesity in animal models, but their role in humans is unclear.Aim: The aim of the study was to characterize the miRNA content in plasma extracellular vesicle isolates after acute and long‐term exercise and to study associations between extracellular vesicle miRNAs, mRNA expression in skeletal muscle and adipose tissue, and cardiometabolic risk factors.Methods: Sedentary men with or without dysglycemia and overweight underwent an acute bicycle test and a 12‐week exercise intervention with extensive metabolic phenotyping. Gene expression in m. vastus lateralis and subcutaneous adipose tissue was measured with RNA sequencing. Extracellular vesicles were purified from plasma with membrane affinity columns or size exclusion chromatography.Results: Extracellular vesicle miRNA profiling revealed a transient increase in the number of miRNAs after acute exercise. We identified miRNAs, such as miR‐652‐3p, that were associated to insulin sensitivity and adiposity. By performing explorative association analyses, we identified two miRNAs, miR‐32‐5p and miR‐339‐3p, that were strongly correlated to an adipose tissue macrophage signature.Conclusion: Numerous miRNAs in plasma extracellular vesicle isolates were increased by exercise, and several miRNAs correlated to insulin sensitivity and adiposity. Our findings warrant future studies to characterize exercise‐induced extracellular vesicles and cargo miRNA to clarify where exercise‐induced extracellular vesicles originate from, and to determine whether they influence metabolic health or exercise adaptation.

Chronic local inflammation of adipose tissue is an important feature of obesity. Serglycin is a proteoglycan highly expressed by various immune cell types known to infiltrate adipose tissue under obese conditions. To investigate if serglycin expression has an impact on diet-induced adipose tissue inflammation, we subjected Srgn^+/+ and Srgn^−/− mice (C57BL/6J genetic background) to an 8-wk high-fat and high-sucrose diet. The total body weight was the same in Srgn^+/+ and Srgn^−/− mice after diet treatment. Expression of white adipose tissue genes linked to inflammatory pathways were lower in Srgn^−/− mice. We also noted reduced total macrophage abundance, a reduced proportion of proinflammatory M1 macrophages, and reduced formation of crown-like structures in adipose tissue of Srgn^−/− compared with Srgn^+/+ mice. Further, Srgn^−/− mice had more medium-sized adipocytes and fewer large adipocytes. Differentiation of preadipocytes into adipocytes (3T3-L1) was accompanied by reduced Srgn mRNA expression. In line with this, analysis of single-cell RNA sequencing data from mouse and human adipose tissue supports that Srgn mRNA is predominantly expressed by various immune cells, with low expression in adipocytes. Srgn mRNA expression was higher in obese compared with lean humans and mice, accompanied by an increased expression of immune cell gene markers. SRGN and inflammatory marker mRNA expression was reduced upon substantial weight loss in patients after bariatric surgery. Taken together, this study introduces a role for serglycin in the regulation of obesity-induced adipose inflammation. Key Points Obese Srgn^−/− mice have reduced adipose tissue inflammation and adipocyte size. Adipose tissue Srgn mRNA is predominantly expressed by resident immune cells. Patients with obesity have increased SRGN mRNA expression in adipose tissue.

Fish is considered an important part of a healthy diet, in part due to the content of long chain omega-3 fatty acids. However, both lean and fatty fish have beneficial health effects, suggesting that micronutrients and proteins may play a role. In a randomised, controlled, cross-over trial, five healthy male participants consumed 5.2 g of protein from either salmon fishmeal or whey. Blood samples were taken before and 30 and 60 min after intake. The concentration of glucose, lipids, hormones and metabolites, including 28 different amino acids and derivatives, were measured in serum or plasma. Cultured HepG2 cells were incubated with or without serum from the participants, and transcriptomic profiling was performed using RNA sequencing. The ingestion of both salmon fishmeal and whey reduced the glucose and triglyceride levels in serum. Protein intake, independent of the source, increased the concentration of 22 amino acids and derivatives in serum. Fishmeal increased the concentration of arginine, methionine, serine, glycine, cystathionine and 2-aminobutyric acid more than whey did. Incubation with postprandial serum resulted in large transcriptomic alterations in serum-fasted HepG2 cells, with the differential expression of >4500 protein coding genes. However, when comparing cells cultivated in fasting serum to postprandial serum after the ingestion of fishmeal and whey, we did not detect any differentially regulated genes, neither with respect to the protein source nor with respect to the time after the meal. The comparable nutrigenomic effects of fishmeal and whey do not change the relevance of fish by-products as an alternative food source.