(TG) requires the activation of fatty acids to long-chain acyl-CoAs (LC-CoA) by the enzyme acyl-CoA synthetase (ACSL). There are five known isoforms of ACSL (ACSL1, -3, -4, -5, -6), which vary in their tissue specificity and affinity for fatty acid substrates. To investigate the role of ACSL1 in the regulation of lipid metabolism, we used adenoviral-mediated gene transfer to overexpress ACSL1 in the human hepatoma cell-line HepG2 and in liver of rodents. Infection of HepG2 cells with the adenoviral construct AdACSL1 increased ACSL activity Ͼ10-fold compared with controls after 24 h. HepG2 cells overexpressing ACSL1 had a 40% higher triglyceride (TG) content (93 Ϯ 3 vs. 67 Ϯ 2 nmol/mg protein in controls, P Ͻ 0.05) after 24-h exposure to 1 mM oleate. Furthermore, ACSL1 overexpression produced a 60% increase in cellular LCA-CoA content (160 Ϯ 6 vs. 100 Ϯ 6 nmol/g protein in controls, P Ͻ 0.05) and increased [ 14 C]oleate incorporation into TG without significantly altering fatty acid oxidation. In mice, AdACSL1 administration increased ACSL1 mRNA and protein more than fivefold over controls at 4 days postinfection. ACSL1 overexpression caused a twofold increase in TG content in mouse liver (39 Ϯ 4 vs. 20 Ϯ 2 mol/g wet wt in controls, P Ͻ 0.05), and overexpression in rat liver increased [1-14 C]palmitate clearance into liver TG. These in vitro and in vivo results suggest a pivotal role for ACSL1 in regulating TG synthesis in liver.acyl-coenzyme A synthetase; hepatic triglyceride synthesis; adenovirus; fatty acid metabolism OBESITY AND ITS ASSOCIATED COMPLICATIONS of insulin resistance, cardiovascular disease, hypertension, hepatic steatosis, and type 2 diabetes have become a major health problem worldwide (50). All of these metabolic disorders exhibit altered regulation of lipid metabolism, which results in the intracellular accumulation of lipid in nonadipose tissues, but the intracellular mechanisms that control partitioning of fatty acids into different metabolic pathways are still being elucidated.Fatty acids can be metabolized in the pathways of -oxidation, triglyceride synthesis, phospholipid synthesis, cholesterol ester synthesis, fatty acid elongation, and protein acylation and can also serve as signaling molecules (7,10,40). It is believed that the partitioning of intracellular fatty acids between storage pathways and -oxidation is controlled by regulation of the mitochondrial acyl-CoA transporter carnitine palmitoyltransferase-1 (32), by regulation of metabolic gene expression (39), and by hormones including insulin. A number of recent studies suggest that partitioning might also involve the different isoforms of acyl-CoA synthetase (ACSL) (7,20,49).ACSL catalyzes the ATP-dependent acylation of fatty acids into long-chain acyl CoAs (LCA-CoAs) and is the first step in lipid metabolism after fatty acid entry into the cell. The LCA-CoAs can then enter the -oxidation pathway for energy production or undergo further esterification for production of phospholipids, cholesterol esters, and triglycerides. Th...
BackgroundAgriculture is facing enormous challenges to feed a growing population in the face of rapidly evolving pests and pathogens. The rusts, in particular, are a major pathogen of cereal crops with the potential to cause large reductions in yield. Improving stable disease resistance is an on-going major and challenging focus for many plant breeding programs, due to the rapidly evolving nature of the pathogen. Sorghum is a major summer cereal crop that is also a host for a rust pathogen Puccinia purpurea, which occurs in almost all sorghum growing areas of the world, causing direct and indirect yield losses in sorghum worldwide, however knowledge about its genetic control is still limited. In order to further investigate this issue, QTL and association mapping methods were implemented to study rust resistance in three bi-parental populations and an association mapping set of elite breeding lines in different environments.ResultsIn total, 64 significant or highly significant QTL and 21 suggestive rust resistance QTL were identified representing 55 unique genomic regions. Comparisons across populations within the current study and with rust QTL identified previously in both sorghum and maize revealed a high degree of correspondence in QTL location. Negative phenotypic correlations were observed between rust, maturity and height, indicating a trend for both early maturing and shorter genotypes to be more susceptible to rust.ConclusionsThe significant amount of QTL co-location across traits, in addition to the consistency in the direction of QTL allele effects, has provided evidence to support pleiotropic QTL action across rust, height, maturity and stay-green, supporting the role of carbon stress in susceptibility to rust. Classical rust resistance QTL regions that did not co-locate with height, maturity or stay-green QTL were found to be significantly enriched for the defence-related NBS-encoding gene family, in contrast to the lack of defence-related gene enrichment in multi-trait effect rust resistance QTL. The distinction of disease resistance QTL hot-spots, enriched with defence-related gene families from QTL which impact on development and partitioning, provides plant breeders with knowledge which will allow for fast-tracking varieties with both durable pathogen resistance and appropriate adaptive traits.Electronic supplementary materialThe online version of this article (doi:10.1186/s12870-014-0366-4) contains supplementary material, which is available to authorized users.
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