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Peripheral blood mononuclear cells (PBMC) provide a useful and minimally invasive source of biomarkers. Here we aimed to identify PBMC transcriptomic biomarkers predictive of metabolic impairment related to increased adiposity.We analysed the global PBMC transcriptome in metabolically healthy (normoglycemic) volunteers with overweight-obesity (OW-OB, n = 12), and in subjects with metabolically-obese normal-weight (MONW, n = 5) phenotype, in comparison to normal weight (NW, n = 12) controls. We identified 1,072 differentially expressed genes (DEGs) in OW-OB versus NW and 992 in MONW versus NW. Hierarchical clustering of the top 100 DEGs clearly distinguished OW-OB and MONW from NW. Remarkably, the OW-OB and MONW phenotypes shared 257 DEGs regulated in the same direction. The top up-regulated gene CXCL8, coding for interleukin 8, with a role in obesity-related pathologies, was of special interest as a potential marker for predicting increased metabolic risk. CXCL8 expression was increased mainly in the MONW group and correlated directly with C-reactive protein levels.PBMC gene expression analysis of CXCL8 or a pool of DEGs might be used to identify early metabolic risk in an apparently healthy population regardless of their BMI, i.e., subjects with OW-OB or MONW phenotype and to apply adequate and personalized nutritional preventive strategies. This article is protected by copyright. All rights reserved.

Scope Distinct markers for mild vitamin B3 deficiency are lacking. To identify these, the molecular responses of white adipose tissue (WAT) to vitamin B3 withdrawal are examined. Methods and results A dietary intervention is performed in male C57BL/6JRccHsd mice, in which a diet without nicotinamide riboside (NR) is compared to a diet with NR at the recommended vitamin B3 level. Both diets contain low but adequate level of tryptophan. Metabolic flexibility and systemic glucose tolerance are analyzed and global transcriptomics, qRT-PCR, and histology of epididymal WAT (eWAT) are performed. A decreased insulin sensitivity and a shift from carbohydrate to fatty acid oxidation in response to vitamin B3 withdrawal are observed. This is consistent with molecular changes in eWAT, including an activated MEK/ERK signaling, a lowering of glucose utilization markers, and an increase in makers of fatty acid catabolism, possibly related to the consistent lower expression of mitochondrial electron transport complexes. The synthesis pathway of tetrahydropteridine (BH4), an essential cofactor for neurotransmitter synthesis, is transcriptionally activated. Genes marking these processes are technically validated. Conclusion The downregulation of Anp32a, Tnk2 and the upregulation of Mapk1, Map2k1, Qdpr, Mthfs, and Mthfsl are proposed as a WAT transcriptional signature marker for mild vitamin B3 deficiency.

Using standardized, semipurified diets is a crucial factor for reproducibility of experimental nutritional studies. For the purpose of comparability and integration of research, two European consortia, Mitofood and BIOCLAIMS, proposed an AIN-93-based standard reference diet, the standardized BIOCLAIMS low-fat diet (LFD) as well as a high-fat diet (HFD). In order to evaluate the BIOCLAIMS LFD and HFD, we performed short-term (5 days) and long-term (12 weeks) feeding experiments using male C57BL/6 mice. The HFD has the same composition as the LFD except the fat content is increased to 40% energy in exchange for carbohydrates. Both diets were accepted by the animals and proof of principle was given that the BIOCLAIMS HFD increases body weight and body fat and affects glucose homeostasis. Short-term feeding trials (5 days) were performed in order to identify metabolic and molecular parameters which can serve as acute predictors for metabolic disorders due to high-fat diet-induced obesity. We analyzed gene expression in gonadal white adipose tissue of short- and long-term fed animals with whole genome microarrays. The BIOCLAIMS HFD strongly influenced gene expression in white adipose tissue after short- and long-term intervention. A total number of 973 and 4678 transcripts were significantly different between both diets after 5 days feeding and 12 weeks feeding, respectively. A total number of 764 transcripts encoding 549 genes were significantly differentially regulated between LF and HF animals after 12 weeks feeding as well as after 5 days feeding. Of these 549 overlapping genes, a substantial number (434 genes) were expressed at a lower level and 115 genes were expressed at a higher level in the HF mice compared to the LF mice. Without exception, all genes were regulated equally. Pathway analysis revealed a prominent role for genes involved in lipid metabolism, carbohydrate metabolism and oxidative phosphorylation. This was confirmed by quantitative real-time reverse transcription PCR. The high predictive value of gene expression changes in our short-term study compared to long-term high fat feeding is a promising step to get well-defined, early biomarkers that could shorten animal trials considerably and allow a more rapid and efficient screening of different compounds.

A primary goal of nutrition research is to optimize health and prevent or delay disease. Biomarkers to quantify health optimization are needed since many if not most biomarkers are developed for diseases. Quantifying "normal homeostasis" and developing validated biomarkers are formidable tasks because of the robustness of homeostasis and of inter-individual diversity. In this paper, we discuss the science, strategies, and technologies for measuring parameters that define individual health. The following concepts are central to define the physiology of the healthy individual: (i) responses to a challenge of homeostasis will be more informative than static homeostatic measures; (ii) processes involved in maintaining homeostasis usually are multi-factorial and require quantitative analyses of the many individual components involved; (iii) health includes a large variation in "normality" and the effects of nutritional interventions may remain hidden in this "diversity of robustness," if incompletely analyzed. Specifically, comprehensive multi-parameter ("omics") analysis may identify key parameters (biomarkers) and lead to a greater understanding of health supporting processes. Perturbation tests that accurately target aspects of the overarching drivers of health (metabolism, oxidation, inflammation, and psychological stress) may be instrumental in creating knowledge for maintaining health and preventing disease through nutrition. © 2009 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

cope : Metabolic programming can occur not only in the perinatal period, but also post-weaning. This study aimed to assess whether fructose, in comparison to glucose, in the post-weaning diet programs body weight, adiposity, glucose tolerance, metabolic flexibility and health at adult age. Methods and results : Three-week-old male and female C57BL6/JRccHsd mice were given an intervention diet with 32 en% glucose or fructose for only three weeks. Next, all animals were switched to the same 40 en% high fat diet for nine weeks. Neither body weight nor adiposity differed significantly between the animals fed glucose or fructose diets at any point during the study in both sexes. Glucose tolerance in adulthood was not affected by the post-weaning diet, nor were activity, energy expenditure and metabolic flexibility, as measured by indirect calorimetry. At the end of the study, only in females fasting serum insulin levels and HOMA-IR index were lower in post-weaning fructose versus glucose diet (p = 0.02), without differences in pancreatic β-cell mass. Conclusions : Our present findings indicate no adverse programming of body weight, adiposity, glucose tolerance and metabolic flexibility by dietary (solid) fructose in comparison to glucose in the post-weaning diet in mice. This article is protected by copyright. All rights reserved