Intra-orogenic Svecofennian magmatism in SW Finland constrained by LA-MC-ICP-MS zircon dating and geochemistry

We have studied plutonic rocks from the Korpo and Rauma areas of south-western Finland which can be categorized as intra-orogenic, i.e. they were intruded during a proposed extensional period between the two main Svecofennian orogenic cycles: the Fennian and Svecobaltic orogenies. The diorite from Rauma yielded an age of 1865 +/- 9 Ma and the diorite from Korpo an age of 1852 +/- 4 Ma. The adjacent garnet-bearing Korpo granite was 1849 +/- 8 Ma in age. Zircons from the granite also included inherited Archaean and older Palaeoproterozic zircons, as well as metamorphic c. 1820 Ma rims. The diorites are high-K to shoshonitic, mantle-derived magmas, rich in Fe, P, F and light rare earth elements. The Korpo granites show typical features of crustal-derived melts and form hybrids with the diorites in contact zones. Both the mantle-derived and crustal-derived intra-orogenic magmatism are considered to have had a causal effect on the subsequent late Svecofennian (Svecobaltic) thermal evolution in southern Finland which culminated in granulite facies metamorphism and large-scale crustal melting.</p

Differential coexpression analysis of obesity-associated networks in human subcutaneous adipose tissue

Objective: To use a unique obesity-discordant sib-pair study design to combine differential expression analysis, expression quantitative trait loci (eQTLs) mapping and a coexpression regulatory network approach in subcutaneous human adipose tissue to identify genes relevant to the obese state. Study design: Genome-wide transcript expression in subcutaneous human adipose tissue was measured using Affymetrix U133 Plus 2.0 microarrays (Affymetrix, Santa Clara, CA, USA), and genome-wide genotyping data was obtained using an Applied Biosystems (Applied Biosystems; Life Technologies, Carlsbad, CA, USA) SNPlex linkage panel. Subjects: A total of 154 Swedish families ascertained through an obese proband (body mass index (BMI) >30 kg m−2) with a discordant sibling (BMI>10 kg m−2 less than proband). Results: Approximately one-third of the transcripts were differentially expressed between lean and obese siblings. The cellular adhesion molecules (CAMs) KEGG grouping contained the largest number of differentially expressed genes under cis-acting genetic control. By using a novel approach to contrast CAMs coexpression networks between lean and obese siblings, a subset of differentially regulated genes was identified, with the previously GWAS obesity-associated neuronal growth regulator 1 (NEGR1) as a central hub. Independent analysis using mouse data demonstrated that this finding of NEGR1 is conserved across species. Conclusion: Our data suggest that in addition to its reported role in the brain, NEGR1 is also expressed in subcutaneous adipose tissue and acts as a central ‘hub’ in an obesity-related transcript network

Skeletal muscle-specific overexpression of SIRT1 does not enhance whole-body energy expenditure or insulin sensitivity in young mice

Aims/hypothesis: The NAD+-dependent protein deacetylase sirtuin (SIRT)1 is thought to be a key regulator of skeletal muscle metabolism. However, its precise role in the regulation of insulin sensitivity is unclear. Accordingly, we sought to determine the effect of skeletal muscle-specific overexpression of SIRT1 on skeletal muscle insulin sensitivity and whole-body energy metabolism. Methods: At 10 weeks of age, mice with muscle-specific overexpression of SIRT1 and their wild-type littermates were fed a standard diet with free access to chow or an energy-restricted (60% of standard) diet for 20 days. Energy expenditure and body composition were measured by indirect calorimetry and magnetic resonance imaging, respectively. Skeletal muscle insulin-stimulated glucose uptake was measured ex vivo in soleus and extensor digitorum longus muscles using a 2-deoxyglucose uptake technique with a physiological insulin concentration of 360 pmol/l (60 &mu;U/ml). Results: Sirt1 mRNA and SIRT1 protein levels were increased by approximately 100- and 150-fold, respectively, in skeletal muscle of mice with SIRT1 overexpression compared with wild-type mice. Despite this large-scale overexpression of SIRT1, body composition, whole-body energy expenditure, substrate oxidation and voluntary activity were comparable between genotypes. Similarly, skeletal muscle basal and insulin-stimulated glucose uptake were unaltered with SIRT1 overexpression. Finally, while 20 days of energy restriction enhanced insulin-stimulated glucose uptake in skeletal muscles of wild-type mice, no additional effect of SIRT1 overexpression was observed. Conclusions/interpretation: These results demonstrate that upregulation of SIRT1 activity in skeletal muscle does not affect whole-body energy expenditure or enhance skeletal muscle insulin sensitivity in young mice on a standard diet with free access to chow or in young mice on energy-restricted diets