Hepatic PGC-1{beta} overexpression induces combined hyperlipidemia and modulates the response to PPAR{alpha} activation

Objective—Previous studies have indicated that the hyperlipidemia and gene expression changes induced by a short-term high-fat diet (HFD) are mediated through the peroxisome proliferator-activated receptor coactivator (PGC)-1, and that in vitro both PGC-1 and PGC 1 increase PPAR-mediated transcriptional activities. Here, we examined the in vivo effects of these two coactivators in potentiating the lipid lowering properties of the PPAR agonist Wy14,643 (Wy). Methods and Results—C57BL/6 mice were fed chow or HFD and transduced with adenoviruses encoding PGC-1 or PGC-1. On chow, hepatic PGC-1 overexpression caused severe combined hyperlipidemia including elevated plasma apolipoprotein B levels. Hepatic triglyceride secretion, DGAT1, and FAT/CD36 expression were increased whereas PPAR and hepatic lipase mRNA levels were reduced. PGC-1 overexpression blunted Wy-mediated changes in expression levels of PPAR and downstream genes. Furthermore, PGC-1 did not potentiate Wy-stimulated fatty acid oxidation in primary hepatocytes. PGC-1 and PGC-1 overexpression did not alter SREBP-1c, SREBP-1c target gene expression, nor hepatic triglyceride content. On HFD, PGC-1 overexpression decreased hepatic SREBP-1c, yet increased FAS and ACC mRNA and plasma triglyceride levels. Conclusions—Hepatic PGC-1 overexpression caused combined hyperlipidemia independent of SREBP-1c activation. Hepatic PGC-1 overexpression reduced the potentially beneficial effects of PPAR activation on gene expression

Evaluation of fractionally distilled Picea abies TMP-turpentine on wood-decaying fungi : in vitro, microcosm and field experiments

Synthetic and heavy metal antifungals are frequently used as wood preservatives. However, they exhibit relatively inert biodegradation and toxic properties when leached; this makes their replacement with environmentally degradable yet functional alternatives a key target in the wood protection industry. In this context, distilled fractions of raw thermomechanical pulp turpentine (TMP-T) from Picea abies were assessed for their wood protecting capabilities against wood-decaying fungi. Antifungal bioactivity of fractions and some of their combinations were screened on agar-plates against the brown-rot fungus Coniophora puteana. Addition of TMP-T fractions showed a significant fungal growth rate reduction, while mixtures indicated the presence of synergistic and antagonistic effects. One fraction, obtained after distilling 1 L TMP-T at 111–177 °C at 0.5 mbar, showed complete growth inhibition of Antrodia sinuosa, Serpula lacrymans, Serpula himantioides and significant inhibition of Antrodia serialis, Antrodia xantha, Gloeophyllum sepiarium, Heterobasidion parviporum at a concentration of 1000 ppm. This fraction was further examined for long- and medium-term effects on wood decay in microcosm soil-jar and field experiment, respectively. The known antifungal compounds benzisothiazolinone, 2-octyl-4-isothiazolin-3-one, 3-iodo-2-propynyl N-butylcarbamate and two commercial wood preservatives were used as reference treatments. Commercial preservatives instilled long-term efficacy against C. puteana wood decay in a soil-jar microcosm experiment, but no noticeable protection with antifungal compounds or the present treatments was found. However, a moderate effect by the TMP-T fraction from the in vitro assay was observed and the TMP-turpentine distillation residue showed a similar fungal inhibition effect to the most potent commercial treatment after 29 months in the field