B arbara Reyn es, Rub en D ıaz-R ua, Margalida Cifre, Paula Oliver, and Andreu Palou Objectives: Peripheral blood mononuclear cells (PBMC) constitute an easily obtainable blood cell fraction useful in nutrition and obesity studies. Our aim was to study the potential use of PBMC to reflect metabolic recovery associated with weight loss in rats. Methods: By real-time PCR, the fasting response of key energy homeostatic genes in PBMC samples of control and cafeteria-obese rats and of rats fed a control diet after the intake of a cafeteria diet (postcafeteria model) was analyzed. Results: Fasting caused decreased mRNA expression of lipogenic (Fasn and Srebp1a) and adipogenic (Pparc) genes in PBMC, whereas it increased the expression of the key beta-oxidation gene Cpt1a and the orexigenic gene Npy. Fasting response of the genes studied was impaired in cafeteria-obese animals but was recovered in post-cafeteria rats, which showed a significant body weight decrease and normalization of adipose and metabolic parameters. Npy expression analyzed in PBMC has been revealed to be especially useful as a marker of fasting sensitivity, as its fasting response is not affected by the age of the animals and it is recovered even after shorter time of exposure to a balanced diet. Conclusions: PBMC reflect homeostatic balance recovery associated with weight loss in obese animals, when reverting from a hyperlipidic to a control balanced diet.

BackgroundMetabolically-obese, normal-weight (MONW) individuals are not obese in terms of weight and height but have a number of obesity-related features (e.g. greater visceral adiposity, insulin resistance, and increased risk of cardiovascular disease). The MONW phenotype is related to the intake of unbalanced diets, such as those rich in fat. Increasing evidence shows a relationship between high-fat diet consumption and mild cognitive impairment and dementia. Thus, MONW individuals could be at a greater risk of cognitive dysfunction. We aimed to evaluate whether MONW-like animals present gene expression alterations in the hippocampus associated with an increased risk of cognitive impairment, and to identify early biomarkers of cognitive dysfunction in peripheral blood mononuclear cells (PBMC).MethodsWistar rats were chronically fed with a 60% (HF60) or a 45% (HF45) high-fat diet administered isocalorically to control animals to mimic MONW features. Expression analysis of cognitive decline-related genes was performed using RT-qPCR, and working memory was assessed using a T-maze.ResultsHigh-fat diet consumption altered the pattern of gene expression in the hippocampus, clearly pointing to cognitive decline, which was accompanied by a worse performance in the T-maze in HF60 animals. Remarkably, Syn1 and Sorl1 mRNA showed the same expression pattern in both the hippocampus and the PBMC obtained at different time-points in the HF60 group, even before other pathological signs were observed.ConclusionsOur results demonstrate that long-term intake of high-fat diets, even in the absence of obesity, leads to cognitive disruption that is reflected in PBMC transcriptome. Therefore, PBMC are revealed as a plausible, minimally-invasive source of early biomarkers of cognitive impairment associated with increased fat intake.Electronic supplementary materialThe online version of this article (10.1186/s13024-018-0246-8) contains supplementary material, which is available to authorized users.

Gene expression profile of peripheral blood cells (PBC) is able to reflect useful aspects of the whole body metabolic status. Therefore, and favored by the huge development of "omic" technologies, blood cells and, particularly, the peripheral blood mononuclear cell (PBMC) fraction, are emerging as a potent source of transcriptomic biomarkers of health and disease. In this review we describe and discuss the available information concerning the use of the PBC and the PBMC fraction as a crucial tool for nutrigenomic studies. Results of these studies reveal, as these cells are good indicators of metabolic adaptations to diet and, moreover, as they allow us to monitor from early stages on, the metabolic alterations associated with dietary imbalances. In this way, blood cells present the capacity of reflecting higher risks of suffering from diet-related pathologies, such as obesity and its medical complications. What is more, different studies also show how PBMC are able to evidence the metabolic recovery associated with weight loss or dietary interventions. Besides, recent research points to the utility of ex vivo systems of blood cells to test the efficacy of food bioactives. All in all, PBC constitutes an easily obtainable source of predictive biomarkers of metabolic imbalance and disease related to diet and obesity, and also of metabolic recovery, which appears as highly relevant for developing nutritional preventive strategies in dietetics. Moreover, they could serve to perform relatively simple and economic in vitro tests to assess food bioactive compounds, promoting in this way functional food research and related industry developments.