Dose- and time-dependent alterations in lipid metabolism after pharmacological PGC-1α activation in L6 myotubes

Pyrroloquinoline quinone (PQQ) acts as a powerful modulator of PGC-1α activation and therefore regulates multiple pathways involved in cellular energy homeostasis. In the present study, we assessed the effects of L6 myotubes incubation with 0.5, 1, and 3 μM PQQ solution for 2 and 24 hr with respect to the cells' lipid metabolism. We demonstrated that PQQ significantly elevates PGC-1α content in a dose- and time-dependent manner with the highest efficiency for 0.5 and 1 µM. The level of free fatty acids was diminished (24 hr: −66%), while an increase in triacylglycerol (TAG) amount was most pronounced after 0.5 μM (2 hr: +93%, 24 hr: +139%) treatment. Ceramide (CER) content was elevated after 2 hr incubation with 0.5 µM and after prolonged exposure to all PQQ concentrations. The cells treated with PQQ for 2 hr exhibited decreased sphinganine (SFA) and sphinganine-1-phosphate (SFA1P) level, while 24 hr incubation resulted in an elevated sphingosine (SFO) amount. In summary, PGC-1α activation promotes TAG and CER synthesis.     

SorCS2 Controls Functional Expression of Amino Acid Transporter EAAT3 and Protects Neurons from Oxidative Stress and Epilepsy-Induced Pathology

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Structural Characterization of CalS8, a TDP-α-d-Glucose Dehydrogenase Involved in Calicheamicin Aminodideoxypentose Biosynthesis

Classical UDP-glucose 6-dehydrogenases (UGDHs; EC 1.1.1.22) catalyze the conversion of UDP-α-d-glucose (UDP-Glc) to the key metabolic precursor UDP-α-d-glucuronic acid (UDP-GlcA) and display specificity for UDP-Glc. The fundamental biochemical and structural study of the UGDH homolog CalS8 encoded by the calicheamicin biosynthetic gene is reported and represents one of the first studies of a UGDH homolog involved in secondary metabolism. The corresponding biochemical characterization of CalS8 reveals CalS8 as one of the first characterized base-permissive UGDH homologs with a >15-fold preference for TDP-Glc over UDP-Glc. The corresponding structure elucidations of apo-CalS8 and the CalS8·substrate·cofactor ternary complex (at 2.47 and 1.95 Å resolution, respectively) highlight a notably high degree of conservation between CalS8 and classical UGDHs where structural divergence within the intersubunit loop structure likely contributes to the CalS8 base permissivity. As such, this study begins to provide a putative blueprint for base specificity among sugar nucleotide-dependent dehydrogenases and, in conjunction with prior studies on the base specificity of the calicheamicin aminopentosyltransferase CalG4, provides growing support for the calicheamicin aminopentose pathway as a TDP-sugar-dependent process.     

Ancient Evolutionary Trade-Offs between Yeast Ploidy States

The number of chromosome sets contained within the nucleus of eukaryotic organisms is a fundamental yet evolutionarily poorly characterized genetic variable of life. Here, we mapped the impact of ploidy on the mitotic fitness of baker''s yeast and its never domesticated relative Saccharomyces paradoxus across wide swaths of their natural genotypic and phenotypic space. Surprisingly, environment-specific influences of ploidy on reproduction were found to be the rule rather than the exception. These ploidy–environment interactions were well conserved across the 2 billion generations separating the two species, suggesting that they are the products of strong selection. Previous hypotheses of generalizable advantages of haploidy or diploidy in ecological contexts imposing nutrient restriction, toxin exposure, and elevated mutational loads were rejected in favor of more fine-grained models of the interplay between ecology and ploidy. On a molecular level, cell size and mating type locus composition had equal, but limited, explanatory power, each explaining 12.5%–17% of ploidy–environment interactions. The mechanism of the cell size–based superior reproductive efficiency of haploids during Li⁺ exposure was traced to the Li⁺ exporter ENA. Removal of the Ena transporters, forcing dependence on the Nha1 extrusion system, completely altered the effects of ploidy on Li⁺ tolerance and evoked a strong diploid superiority, demonstrating how genetic variation at a single locus can completely reverse the relative merits of haploidy and diploidy. Taken together, our findings unmasked a dynamic interplay between ploidy and ecology that was of unpredicted evolutionary importance and had multiple molecular roots.     

Anthropometry and Body Composition of Adolescents in Cracow,Poland

Background and Objective

The aim of the present study was to determine the level of adiposity and obesity in Polish adolescents and compare the results with earlier studies conducted in this population as well as those carried out in other populations.

Methods

The study group consisted of 456 boys and 514 girls aged 14-18 years living in Cracow chosen from randomly selected secondary schools. Weight, height, waist, and hip circumference (WC, HC) as well as triceps, biceps, subscapular, and suprailiac skinfold thickness (SFT) were measured. Body mass index (BMI), waist-to-hip ratio (WHR), waist-to-height ratio (WHtR), subscapular/triceps skinfold ratio (STR), and percentage body fat were computed. The prevalence of overweight and obesity based on Polish children growth reference were calculated and age-dependent and gender-specific smoothed percentile curves for BMI and ROC curves were generated.

Results

Weight, height, WC, HC (up 16yr), WHtR (up 15yr), and WHR were considerably higher in males than females. Weight, height, and HC increased with age; WHtR remained the same. The prevalence of overweight and obesity were 10.2% (boys 10.3%; girls 10.1%) and 4.2% (boys 5.3%; girls 3.3%). ROC analysis revealed that WHtR was the best tool for detection of obesity (AUC of 0.982±0.007) in males, whereas the sum of four SFTs (AUC: 0.968±0.011) and WHtR (AUC: 0.963±0.012) were the best predictors of obesity in females.

Conclusions

The level of adiposity in Cracow adolescents increased during the last decade. However, it is still lower than in other well-developed societies struggling with obesity epidemics.