Title: Sex-specific alterations in mRNA level of key lipid metabolism enzymes in skeletal muscle of overweight and obese subjects following endurance exercise Smith IJ, Huffman KM, Durheim MT, Duscha BD, Kraus WE Ref: Physiol Genomics, 36:149, 2009 : PubMed
Endurance exercise (EE) leads to beneficial alterations in skeletal muscle lipid metabolism in overweight and obese individuals; however, the mechanisms of these improvements are poorly understood. The primary goal of the current investigation was to test the hypothesis that long-term EE training (6 mo) leads to alterations in the mRNA abundance of key lipid metabolism enzymes in skeletal muscle of overweight and obese middle-aged women and men. A secondary aim of this study was to investigate the hypothesis that exercise-mediated adaptations in mRNA levels differ between women and men. The mRNA abundance of representative lipogenic and lipolytic genes from major lipid metabolism pathways, as well as representative lipogenic and lipolytic transcription factors, were determined by real-time PCR from skeletal muscle biopsies collected before and approximately 24 h after the final bout of 6 mo of EE. Six months of EE led to increases in muscle lipoprotein lipase, peroxisome proliferator-activated receptor-gamma coactivator-1alpha, carnitine palmitoyltransferase-1 beta, diacylglycerol acyltransferase-1, and acid ceramidase mRNA in women, but not men. In contrast, in men, EE led to reductions in the mRNA content of the lipogenic factors sterol regulatory element binding protein-1c and serine palmitoyl transferase. These data suggest that EE-mediated alterations in the abundance of the lipid metabolism genes studied here are fundamentally different between overweight and obese middle-aged women and men. Future studies should determine whether these adaptations in mRNA levels translate into changes in protein function.
Platelet-activating factor acetylhydrolase (PLA2G7) is a potent pro- and anti-inflammatory molecule that has been implicated in multiple inflammatory disease processes, including cardiovascular disease. The goal of this study was to investigate the genetic effects of PLA2G7 on coronary artery disease (CAD) risk in two large, independent datasets with CAD. Using a haplotype tagging (ht) approach, 19 ht single nucleotide polymorphisms (SNPs) were genotyped in CATHGEN case-control samples (cases = 806 and controls = 267) and in the GENECARD Family Study (n = 1101 families, 2954 individuals). Single SNP analysis using logistic regression revealed nine SNPs with significant association in all CATHGEN subjects (P = 0.0004-0.02). CATHGEN cases were further stratified into subgroups based on age of CAD onset (AOO) and severity of disease; 599 young affecteds (YA, AOO <56) and 207 old affected (OA, AOO >56). Significant genetic effects were observed in both OA and YA (P = 0.0001-0.02). The GENECARD probands demonstrated results similar to those seen in the YA CATHGEN cases (P = 0.002-0.05). Of the 19 SNPs genotyped, 3 SNPs result in nonsynonymous coding changes (I198T, A379V and R92H). Two of the coding SNPs, R92H and A379V, constitute two of the most significantly associated SNPs, even after Bonferroni correction and appear to represent independent associations (r(2) = 0.09). Multiple additional polymorphisms in low linkage disequilibrium with these coding SNPs were also strongly associated. In summary, PLA2G7 represents an important, potentially functional candidate in the pathophysiology of CAD based on replicated associations using two independent datasets and multiple statistical approaches. Further functional studies involving a combination of risk alleles are warranted.
