Transcriptomics,Genomics

Dataset Information

31

Identification of early transcriptome-based biomarkers related to lipid metabolism in peripheral blood mononuclear cells of rats nutritionally programmed for improved metabolic health


ABSTRACT: Moderate maternal calorie restriction during lactation protects rat offspring against obesity development in adulthood, due to an improved ability to handle and store excess dietary fuel. We used this model to identify early transcriptome-based biomarkers of metabolic health using peripheral blood mononuclear cells (PBMCs), an easily accessible surrogate tissue, by focusing on molecular markers of lipid handling. Male and female offspring of control and 20 % calorierestricted lactating dams (CR) were studied. At weaning, a set of pups was killed, and PBMCs were isolated for whole-genome microarray analysis. The remaining pups were killed at 6 months of age. CR gave lower body weight, food intake and fat accumulation, and improved levels of insulin and leptin throughout life, particularly in females. Microarray analysis of weaned rat PBMCs identified 278 genes significantly differentially expressed between control and CR. Among lipid metabolism-related genes, expression of Cpt1a, Lipe and Star was increased and Fasn, Lrp1 and Rxrb decreased in CR versus control, with changes fully confirmed by qPCR. Among them, Cpt1a, Fasn and Star emerged as particularly interesting. Transcript levels of Cpt1a in PBMCs correlated with their levels in WAT and liver at both ages examined; Fasn expression levels in PBMCs at an early age correlated with their expression levels in WAT; and early changes in Star expression levels in PBMCs correlated with their expression levels in liver and were sustained in adulthood. These findings reveal the possibility of using transcript levels of lipid metabolism-related genes in PBMCs as early biomarkers of metabolic health status. Overall design: The study was conducted on male and female Wistar rats from 16 different litters. All animals were housed under standard conditions of controlled temperature (22 _C), the normal 12 h light and 12 h dark cycle, free access to tap water and a standard chow diet (3 kcal/g, with 8 % calories from fat; Panlab, Barcelona, Spain), unless specified otherwise. Briefly, 16 virgin female Wistar rats (body weight 225–260 g) were mated with male rats (Charles River Laboratories, Barcelona, Spain). After mating, each female was placed in an individual cage. On day 1 after delivery, excess pups in each litter were removed aiming for 10 pups per dam (five males and five females, when possible). Dams were assigned to either the control (n = 11 dams) or calorie-restricted (n = 5 dams) group. Control dams were fed ad libitum with standard chow diet, while calorie-restricted dams were fed daily with a 20 % calorie-restricted diet throughout lactation, starting on day 1 after delivery until weaning (day 21) as previously described (Palou et al. 2012). During the lactating period, body weight of male and female offspring of control and calorie-restricted dams (control and CR, respectively) was followed. At weaning at age 21 days, a set of animals made up of 24 pups from control (12 males and 12 females) and 24 from CR (12 males and 12 females) group were killed by decapitation under ad libitum feeding conditions. One half of pups (n = 6/group) were used to obtain trunk blood samples for peripheral blood mononuclear cells (PBMCs) isolation. Another set of animals, 28 control pups (12 males and 16 females) and 26 CR pups (14 males and 12 females), were kept alive. They were placed two per cage, paired with another animal of the same group and fed ad libitum with a normal-fat (NF) diet (3.8 kcal/g, 10 % calories from fat, Research Diets, Inc., NJ, USA) until the age of 6 months. Body weight and food intake of those animals were followed. Moreover, at the age of 6 months (prior to sacrifice), blood samples were collected at fed state and after 12 h fasting to obtain plasma. All the animals were decapitated under ad libitum feeding conditions at the age of 6 months, and samples of trunk blood for PBMCs isolation were collected. Body length (from the tip of the nose to the anus) and body composition (by EchoMRI-700TM, Echo Medical Systems, LLC, TX, USA) were measured in control and CR animals without anesthesia when animals were 21 days and 6 months old. PBMCs were collected using heparin in NaCl (0.9%) as anticoagulant and then diluted with equal volume of balanced salt solution, and separated using Ficoll density gradient.

INSTRUMENT(S): Agilent-014879 Whole Rat Genome Microarray 4x44K G4131F (Feature Number version)

SUBMITTER: Evert M. van Schothorst  

PROVIDER: GSE119955 | GEO | 2018-09-15

REPOSITORIES: GEO

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Identification of early transcriptome-based biomarkers related to lipid metabolism in peripheral blood mononuclear cells of rats nutritionally programmed for improved metabolic health.

Konieczna J J   Sánchez J J   van Schothorst E M EM   Torrens J M JM   Bunschoten A A   Palou M M   Picó C C   Keijer J J   Palou A A  

Genes & nutrition 20131217 1


Moderate maternal calorie restriction during lactation protects rat offspring against obesity development in adulthood, due to an improved ability to handle and store excess dietary fuel. We used this model to identify early transcriptome-based biomarkers of metabolic health using peripheral blood mononuclear cells (PBMCs), an easily accessible surrogate tissue, by focusing on molecular markers of lipid handling. Male and female offspring of control and 20 % calorie-restricted lactating dams (CR  ...[more]

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