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.

Beneficial Effects of Pterocarpan-High Soybean Leaf Extract on Metabolic Syndrome in Overweight and Obese Korean Subjects: Randomized Controlled Trial

“…In addition, the transcriptome or gene expression analysis in PBMCs can reveal information on the lipid metabolism in obesity-associated organs, adipose tissue, and the liver [11]. …”

NMR-based metabolomics highlights differences in plasma metabolites in pigs exhibiting diet-induced differences in adiposity

“…Advances in high-throughput technologies offer new opportunities to investigate the relationships between blood traits and body adiposity. Recent studies have shown differential expressions of several genes in blood peripheral cells that are associated with lipid handling in rats [3] and that are correlated with the development of visceral adiposity in humans [4]. Plasma proteomic profiles have…”

The intake of a high-fat diet and grape seed procyanidins induces gene expression changes in peripheral blood mononuclear cells of hamsters: capturing alterations in lipid and cholesterol metabolisms

“…Afman et al 2014). Furthermore, it has been shown that PBMCs can act as biomarkers of the metabolic adaptations that occur in different tissues such as adipose tissue, liver and muscle (Caimari et al 2010a;Rudkowska et al 2011;Oliver et al 2013;O'Grada et al 2013;Konieczna et al 2014), although there are some controversial results about this issue (Rudkowska et al 2011;O'Grada et al 2013;Afman et al 2014). In addition, other studies have demonstrated that PBMCs can reflect gene expression signatures that are characteristic of different diseases linked to a sedentary lifestyle and increased food intake, such as atherosclerosis (Kang et al 2006), chronic heart failure (Cappuzzello et al 2009) and metabolic syndrome (D'Amore et al 2013).…”