Free fatty acids regulate gluconeogenic gene induction in rat hepatocytes

Free fatty acids regulate gluconeogenic gene induction in rat hepatocytes

S30 Abstracts / Chemistry and Physics of Lipids 164S (2011) S28–S31 P 26 Free fatty acids regulate gluconeogenic gene induction in rat hepatocytes ...

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S30

Abstracts / Chemistry and Physics of Lipids 164S (2011) S28–S31

P 26 Free fatty acids regulate gluconeogenic gene induction in rat hepatocytes

cess lead to decrease tissue TAG levels. Another process to decrease TAG is known to be due to the suppression of fatty acid synthesis by polyunsaturated fatty acids.

Noga Budick-Harmelin ∗ , Zecharia Madar, Oren Tirosh

doi:10.1016/j.chemphyslip.2011.05.098

Institute of Biochemistry, Food Science and Nutrition, The Hebrew University of Jerusalem, Israel

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Hepatic gluconeogenesis tightly controls blood glucose levels in healthy individuals, yet disorders of fatty acids (FAs) oxidation are characterized by hypoglycemia.We studied the ability of FAs to directly regulate gluconeogenic gene expression, as a novel mechanism that elucidates the hypoglycemic effect of FAs oxidation disorders. Primary rat hepatocytes and FaO hepatoma cell cultures were pre-treated with FAs prior to gluconeogenic stimuli. Pre-treatment with 1 mM FAs (mixture of 2:1 oleate/palmitate) for 1 h prior to gluconeogenic induction, significantly decreases the induced expression of the gluconeogenic genes phosphoenolpyruvate carboxykinase (PEPCK) and glucose-6-phosphatase (G6pase) in both cell types. The inhibitory effect of FAs upon gluconeogenesis is abolished when pre-treatment is elongated to 18 h, allowing clearance of FAs into triglycerides (TGs) by the cells. Replacement of palmitate with the non-metabolic fatty acid 2bromopalmitate inhibits esterification of FAs into TGs. Accordingly, the increased exposure to unesterified-FAs allows their inhibitory effect to be extended even when pre-treatment is elongated to 18 h. The inhibitory effect of FAs is mediated by regulation of PGC1␣ gene expression and by cAMP response element-binding (CREB) activation. We conclude that FAs directly inhibit induced gluconeogenic gene expression in hepatocytes. Hence, free-FAs may facilitate hypoglycemia among patients with metabolic defects in FAs oxidation. doi:10.1016/j.chemphyslip.2011.05.097 P 27 Effects of dietary fat on gene expressions of indices of lipid and energy metabolism in visceral adipose tissues of rats Hitomi Fukuda, Mika Kohno, Tomoe Hirakawa, Nobuko Iritani ∗ Department of Human Sciences, Tezukayama Gakuin University, Sakai, Osaka, Japan To investigate biological characteristics of visceral adipose tissues, we have compared the effects of dietary fat on the gene expressions of indices of lipid and energy metabolism of visceral adipose tissues in rats. We measured the mRNA exressions of epidydimal (Epi), perirenal (Per) and mesenteric (Mes) adipose tissues of male rats fed a 10 or 20 wt% corn oil or lard diet for 2 weeks. The adipose tissue weights and the plasma and liver triacylglycerol (TAG) concentrations were lower in rats fed corn oil than in those fed lard. The UCP2 mRNA expressions were higher in rats fed corn oil as compared with lard in Mes. The plasma insulin levels and the adipose tissue insulin receptor expressions were not significantly different between the corn oil and lard groups, while the insulin receptor expressions was significantly higher in Mes than in the other adipose tissues. The adiponectin mRNA concentrations tended to be higher in Mes than in the others, and were higher in rats fed the 20% corn oil diet than in those fed the 10%, in Epi and Per. The PPAR␥ exressions were higher similarly to the adiponectin in those fed the 20%, in Epi and Per. Thus it appeared that adiponectin and PPAR␥ increased expression of molecules involved energy dissipation such as UCP2 (not similarly among the adipose tissues) and these pro-

Characterizing the transcriptional circuitry of global lipid metabolism Adam Stefanko 1,∗ , Kilrill Tarasov 2 , Michal Surma 3 , Christer Ejsing 1 1

Department of Biochemistry and Molecular Biology, University of Southern Denmark, Odense, Denmark 2 Zora Biosciences Oy, Espoo, Finland 3 Max Planck Institute of Molecular Cell Biology and Genetics, Dresden, Germany The lipidome of eukaryotic cells comprises hundreds to thousands of individual lipid species that constitute membranes, store metabolic energy and function as bioactive molecules. Despite good understanding of lipid structures, little is known about how the compositional complexity of lipids influences cell physiology. Recent technological development especially in mass spectrometry and bioinformatics has enabled the global and quantitative analysis of molecular lipid species on lipiome-wide scale. To address the question how cells regulate the level of lipid species and how cells govern lipid homeostasis we decided to characterize the transcriptional network of global lipid metabolism in yeast Saccharomyces cerevisiae. For this purpose more than two hundred deletion mutants devoid of distinct transcription factors were culture in 96 well plates. High throughput lipidomics screening was designed to profile the lipidome of the transcription factor mutants. This novel high content screening platform revealed several novel transcription factors with previously unknown roles in the regulation of global lipid metabolism. The phenotypes of gene knockouts were sorted into three distinct phenotypic classes. Some of these phenotypes are conserved in mammalian cells, suggesting that the output from presented studies is likely to be central for better understanding of excessive lipid metabolism deregulation consequences in etiology of obesity, diabetes, fatty liver disease and atherosclerosis. doi:10.1016/j.chemphyslip.2011.05.099 P 29 Characterisation of ACOT9: A CoA/myristoyl-CoA thioesterase

mitochondrial

propionyl-

Veronika Tillander 1,∗ , Elisabet Arvidsson Nordstöm 1 , Jenny Reilly 2 , Mary C. Hunt 2 , Stefan E.H. Alexson 1 1

Karolinska Institute, Department of Laboratory Medicine, Division of Clinical Chemistry, Stockholm, Sweden 2 Dublin Institute of Technology, School of Biological Sciences, Dublin, Ireland Acyl-CoA thioesterases (ACOTs) is a group of enzymes that are found in e.g. peroxisomes, mitochondria and cytosol where they regulate concentrations of fatty acids and acyl-CoAs due to hydrolysis of acyl-CoAs. Mouse ACOT9 is a mitochondrial enzyme that was initially identified as MT-ACT48 by Poupon et al. in 1999. At that time, ACOT9 was characterised as a long-chain ACOT although only a few substrates were tested on immuno-precipitated ACOT9. We expressed ACOT9 in bacteria and characterisation of recombinant ACOT9 showed unusual substrate specificity with two peaks