Identification of blood cell transcript-based early biomarkers of metabolic health in an animal model less prone to obesity

Background and objectives: Moderate maternal calorierestriction during lactation has been shown to protect rat offspring against obesity development in adulthood, due to an improved capacity to handle and store excess dietary fuel. We used this model to find early biomarkers of metabolic health, focusing on molecular markers of lipid handling. To identify transcript based biomarkers we used peripheral blood mononuclear cells (PBMCs), which are easily accessible in humans. Methods: Male and female offspring of control and 20% calorie-restricted lactating dams (CR) were studied. At weaning, a set of pups were killed, PBMCs were isolated and whole genome microarray analysis was performed. White adipose tissue (WAT) and liver were also collected for mRNA expression analyses by qRT-PCR. The remainder of the pups were sacrificed at the age of 6 months. Results: CR-animals displayed lower body weight, food intake and fat accumulation, and improved levels of insulin, leptin and leptin/adiponectin ratio in plasma throughout life. Microarray analysis of weaned rat PBMCs identified 278 genes differentially expressed between the CR and control groups (=0.01). Among lipid metabolism-related genes, expression of Fasn and Rxrb was decreased and Cpt1a and Lipe increased in CR animals versus controls, and changes were fully confirmed by qRT-PCR. At an early age Fasn and Cpt1a expression levels in PBMCs correlated with their expression levels in WAT. Notably, Cpt1a expression in PBMCs correlated with hepatic expression at all time points examined, even in adult animals. Conclusions: These findings reveal the possibility of using transcript levels of lipid metabolism-related genes in PBMCs as early biomarkers of metabolic status, potentially providing a valid biological readout for the study of metabolic processes in humans.