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INTRODUCTION : L’hyperplasie macronodulaire bilatérale des surrénales (HMBS) GIP-dépendante avec syndrome de Cushing est due à l’expression ectopique du récepteur du GIP (GIPR) dans ces lésions surrénaliennes. Notre objectif était d’identifier la cause moléculaire de cette pathologie. [...]

Deficiency of fatty acid translocase Cd36 has been shown to have a major role in the pathogenesis of metabolic syndrome in the spontaneously hypertensive rat (SHR). We have tested the hypothesis that the effects of Cd36 mutation on the features of metabolic syndrome are contextually dependent on genomic background. We have derived two new congenic strains by introgression of limited chromosome 4 regions of SHR origin, both including the defective Cd36 gene, into the genetic background of a highly inbred model of insulin resistance and dyslipidemia, polydactylous (PD) rat strain. We subjected standard diet-fed adult males of PD and the congenic PD.SHR4 strains to metabolic, morphometric and transcriptomic profiling. We observed significantly improved glucose tolerance and lower fasting insulin levels in PD.SHR4 congenics than in PD. One of the PD.SHR4 strains showed lower triglyceride concentrations across major lipoprotein fractions combined with higher levels of low-density lipoprotein cholesterol compared with the PD progenitor. The hepatic transcriptome assessment revealed a network of genes differentially expressed between PD and PD.SHR4 with significant enrichment by members of the circadian rhythmicity pathway (Arntl (Bmal1), Clock, Nfil3, Per2 and Per3). In summary, the introduction of the chromosome 4 region of SHR origin including defective Cd36 into the PD genetic background resulted in disconnected shifts of metabolic profile along with distinct changes in hepatic transcriptome. The synthesis of the current results with those obtained in other Cd36-deficient strains indicates that the eventual metabolic effect of a deleterious mutation such as that of SHR-derived Cd36 is not absolute, but rather a function of complex interactions between environmental and genomic background, upon which it operates.

Introduction: Thiazolidinediones are increasingly used drugs for the treatment of Type 2 diabetes. The individual response to thiazolidinedione therapy, ranging from the variable degree of metabolic improvement to harmful side-effects, is empirical, yet the underlying mechanisms remain elusive. In order to assess the pharmacogenomic component of thiazolidinediones’ metabolic action, we compared the effect of rosiglitazone in two genetically defined models of metabolic syndrome, polydactylous (PD) and BN.SHR4 inbred rat strains, with their insulin-sensitive, normolipidemic counterpart, the Brown Norway (BN) rat. Materials & Methods: 5-month-old male rats were fed a high-fat diet for 4 weeks, and the experimental groups received rosiglitazone (0.4 mg/100 g body weight) during the last 2 weeks of high-fat diet feeding. We assessed metabolic and morphometric profiles, oxidative stress parameters and gene expression in white adipose tissue. Results: In many followed parameters, we observed genetic background-specific effects of rosiglitazone administration. The mass and the sensitivity of visceral adipose tissue to insulin-stimulated lipogenesis increased with rosiglitazone treatment only in PD, correlating with a PD-specific significant increase in expression of prostaglandin D2 synthase. The glucose tolerance was enhanced in all strains, although fasting plasma glucose was increased by rosiglitazone in BN and BN.SHR4. Among the markers of lipid peroxidation, we observed the rosiglitazone-driven increase of plasma-conjugated dienes only in BN.SHR4. The genes with genotype-specific expression change included ADAM metallopeptidase domain 7, aquaporin 9, carnitine palmitoyltransferase 1B, caveolin 1, catechol-O-methyl transferase, leptin and prostaglandin D2 synthase 2. Conclusion: Rosiglitazone’s effects on lipid deposition and insulin sensitivity of peripheral tissues are largely dependent on the genetic background it acts upon.

International audience; The purpose of the study was to test the ability to determine the velocity associated with peak oxygen uptake for adolescents by means of a simple field test, the Université de Montréal Track Test (UMTT). Fifteen adolescents, 13.4 +/- 1.0 years, performed two maximal field tests where oxygen uptake and heart rate were continuously monitored. The first test (graded field test, first stage 8 km.h-1, increment 1.5 km.h-1, duration 3 min) allowed the subjects to reach a steady-state oxygen uptake. Then, the velocity associated with peak oxygen uptake was calculated from the ratio between peak oxygen uptake above resting level to energy cost of running. The calculated velocity was kept as the criterion velocity. For the second test (UMTT, first stage 8 km.h-1; increment 1 km.h-1; duration 2 min), the velocity measured at the last completed stage was retained. The measured peak oxygen uptake for the graded field test (51.8 +/- 6.5 ml.kg-1.min-1) and for the UMTT (51.0 +/- 7.9 ml.kg-1.min-1) were not significantly different. The calculated velocity (12.9 +/- 1.0 km.h-1) and the measured velocity (12.7 +/- 0.9 km.h-1) were not significantly different and were significantly correlated (r = 0.80, p < 0.001). It was concluded that, for adolescents, the velocity measured at the last completed stage of the UMTT allows a valid estimation of the velocity associated with peak oxygen uptake.

International audience; The aims of this study were to use the Maximal Aerobic Speed (MAS) to set training intensities for aerobic training and to measure the effects of two different training programmes on MAS and on the running time to exhaustion at 100% of MAS (Tlim) for 121 students aged 14 to 17 years. The MAS was measured using the Université de Montréal Track Test (UMTT). This measurement was found reproducible for males (r = 0.93) and females (r = 0.68). The Students followed a 12-week training programme of one weekly training session. The MAS and the Tlim were measured the weeks before and after training. Two training programmes were proposed (intense training programme and moderate training programme). These training programmes differed by the ratio between continuous exercises (85% of MAS) and intermittent exercise (between 90% and 120% of MAS). For the moderate training programme, the ratio between continuous and intermittent exercises was greater than for the intensive training programme. Twenty subjects served as control group. The students MAS and Tlim (mean +/- SD) were respectively 13.7 +/- 1.6 km.h-1 and 380.5 +/- 91.8 s for the males and 11.3 +/- 1.2 km.h-1 and 347.2 +/- 91.1 s for the females. Our results indicated that only the subjects of the intense training group improved their MAS: + 5.7% for the males (p < 0.001) and + 5.4% for the females (p < 0.001). In neither case was Tlim significantly improved with training. In conclusion, we can notice that MAS is a pertinent criterion to set training intensities for aerobic training and that a weekly training session over 12 weeks is sufficient to moderately improve the MAS of initially untrained students.