Hepatic de novo synthesis of glucose 6-phosphate is not affected in peroxisome proliferator-activated receptor alpha-deficient mice but is preferentially directed toward hepatic glycogen stores after a short term fast

Apart from impaired beta-oxidation, Pparalpha-deficient (Pparalpha(-/-)) mice suffer from hypoglycemia during prolonged fasting, suggesting alterations in hepatic glucose metabolism. We compared hepatic glucose metabolism in vivo in wild type (WT) and Pparalpha(-/-) mice after a short term fast, applying novel isotopic methods. After a 9-h fast, mice were infused with [U-C-13] glucose, [2-C-13] glycerol, [1-H-2]galactose, and paracetamol for 6 h, and blood and urine was collected in timed intervals. Plasma glucose concentrations remained constant and were not different between the groups. Hepatic glycogen content was 69 +/- 11 and 90 +/- 31 mumol/g liver after 15 h of fasting in WT and Pparalpha(-/-) mice, respectively. The gluconeogenic flux toward glucose 6-phosphate was not different between the groups (i.e. 157 +/- 9 and 153 +/- 9 mumol/kg/min in WT and Pparalpha(-/-) mice, respectively). The gluconeogenic flux toward plasma glucose, however, was decreased in PPARalpha(-/-) mice (i.e. 142 +/- 9 versus 124 +/- 13 mumol/kg/min) (p <0.05), accounting for the observed decrease (-15%) in hepatic glucose production in Pparα(-/-) mice. Expression of the gene encoding glucose-6-phosphate hydrolase (G6ph) was lower in the PPARα(-/-) mice compared with WT mice. In conclusion, Pparα(-/-) mice were able to maintain a normal total gluconeogenic flux to glucose 6-phosphate during moderate fasting, despite their inability to up-regulate β-oxidation. However, this gluconeogenic flux was directed more toward glycogen, leading to a decreased hepatic glucose output. This was associated with a down-regulation of the expression of G6ph in PPARα-deficient mice

Aminoacyl-tRNA synthetase deficiencies: in search of common themes

24. MISCELLANEOUS / NEW DISEASE GROUP : Oral / Poste

Aminoacyl-tRNA synthetase deficiencies: in search of common themes

24. MISCELLANEOUS / NEW DISEASE GROUP : Oral / Poste

Electrophysiological correlates of object location and object identity processing in spatial scenes

Contains fulltext : 102496.pdf (publisher's version ) (Open Access)The ability to quickly detect changes in our surroundings has been crucial to human adaption and survival. In everyday life we often need to identify whether an object is new and if an object has changed its location. In the current event-related potential (ERP) study we investigated the electrophysiological correlates and the time course in detecting different types of changes of an objecṫs location and identity. In a delayed match-to-sample task participants had to indicate whether two consecutive scenes containing a road, a house, and two objects, were either the same or different. In six randomly intermixed conditions the second scene was identical, one of the objects had changed its identity, one of the objects had changed its location, or the objects had switched locations. The results reveal different time courses for the processing of identity and location changes in spatial scenes. Whereas location changes elicited a posterior N2 effect, indicating early mismatch detection, followed by a P3 effect reflecting post-perceptual processing, identity changes elicited an anterior N3 effect, which was delayed and functionally distinct from the N2 effect found for the location changes. The condition in which two objects switched position elicited a late ERP effect, reflected by a P3 effect similar to that obtained for the location changes. In sum, this study is the first to cohesively show different time courses for the processing of location changes, identity changes, and object switches in spatial scenes, which manifest themselves in different electrophysiological correlates.9 p