Peroxisome proliferator activated receptor gamma 2 modulates late pregnancy homeostatic metabolic adaptations.

Pregnancy requires the adaptation of maternal energy metabolism including expansion and functional modifications of adipose tissue. Insulin resistance (IR), predominantly during late gestation, is a physiological metabolic adaptation that serves to support the metabolic demands of fetal growth. The molecular mechanisms underlying these adaptations are not fully understood and may contribute to gestational diabetes mellitus.

Leptin drives fat distribution during diet-induced obesity in mice.

Objective: Desensitization of leptin receptors is a process that specifically occurs in some tissues. We have hypothesized that during the development of obesity tissue lipids would increase gradually in particular organs depending on leptin responsiveness. Our aim was to establish a relationship between leptin resistance and lipid deposition by using a model of diet-induced obesity (DIO) and we have characterized, in mice undergoing a dietary treatment with a high-fat (HF) diet, the evolution of lipid content and leptin responsiveness in white adipose tissue and liver.

Enhanced utilization of glycerol for glyceride synthesis in isolated adipocytes from early pregnant rats.

Adipose tissue normally has low glycerol kinase activity, but its expression is enhanced under conditions of augmented insulin sensitivity and/or obesity. Since these conditions occur during early pregnancy, the comparative utilization of glucose or glycerol by isolated adipocytes from rats at 0, 7, 14, or 20 days of pregnancy was studied. Incubations were carried out in the presence of [U(14)C]-glucose or -glycerol in medium supplemented or not with 5 mM glucose and 100 nM insulin.

Pharmacological and gene modification-based models for studying the impact of perinatal metabolic disturbances in adult life.

Genetic modification approaches or pharmacological interventions may be useful for understanding the molecular mechanisms by which nutrient derivatives and metabolites exert their effects in the perinatal period and how they may influence longterm metabolism in adults. Examples for such experimental settings in rodents are targeted disruption of the gene for peroxisome proliferator-activated receptor (PPAR)-a, a lipid sensor and master regulator of lipid catabolism, or maternal treatment with agonists of PPARgamma, a master regulator of adipogenesis and target of insulin sensitizing drugs in adults. All these interventions show differential effects in the perinatal period compared to adults and indicate that altered activity of master regulators of metabolism results in profound metabolic alterations in the perinatal period that may influence adult metabolism.

Morphine differentially regulates hsp90beta expression in the nucleus accumbens of Lewis and Fischer 344 rats.

We have comparatively studied hsp90beta gene and protein expression in the nucleus accumbens of Lewis and Fischer 344 (F344) rats, two inbred strains that exhibit prominent behavioural differences in drug-seeking behaviours. Phenotypical studies confirmed that Lewis rats developed a higher preference for morphine-paired environments after conditioning. RT-PCR assays did not reveal strain-related differences in hsp90beta gene expression in basal conditions; however, acute morphine treatment provoked an increase of hsp90beta mRNA 2h after injection only in the case of Lewis rats.

Englitazone administration to late pregnant rats produces delayed body growth and insulin resistance in their fetuses and neonates.

The level of maternal circulating triacylglycerols during late pregnancy has been correlated with the mass of newborns. PPARgamma (peroxisome-proliferator-activated receptor gamma) ligands, such as TZDs (thiazolidinediones), have been shown to reduce triacylglycerolaemia and have also been implicated in the inhibition of tissue growth and the promotion of cell differentiation. Therefore TZDs might control cell proliferation during late fetal development and, by extension, body mass of pups.