Olga Horakova - Academia.edu (original) (raw)

Papers by Olga Horakova

FEBS letters, 2004

The AMP-activated protein kinase (AMPK) cascade is a sensor of cellular energy charge that promot... more The AMP-activated protein kinase (AMPK) cascade is a sensor of cellular energy charge that promotes catabolic and inhibits anabolic pathways. However, the role of AMPK in adipocytes is poorly understood. We show that transgenic expression of mitochondrial uncoupling protein 1 in white fat, which induces obesity resistance in mice, is associated with depression of cellular energy charge, activation of AMPK, downregulation of adipogenic genes, and increase in lipid oxidation. Activation of AMPK may explain the complex metabolic changes in adipose tissue of these animals and our results support a role for adipocyte AMPK in the regulation of storage of body fat.

Genes & nutrition, 2012

Experimental replication is fundamental for practicing science. To reduce variability, it is esse... more Experimental replication is fundamental for practicing science. To reduce variability, it is essential to control sources of variation as much as possible. Diet is an important factor that can influence many processes and functional outcomes in studies performed with rodent models. This is especially true for, but not limited to, nutritional studies. To compare functional effects of different nutrients, it is important to use standardized, semi-purified diets. Here, we propose and describe a standard reference diet, the BIOCLAIMS standard diet. The diet is AIN-93 based, but further defined with dietary and experimental requirements taken into account that allow for experiments with bioactive food components and natural (non-expensive) labeling. This diet will be implemented by two European research consortia, Mitofood and BIOCLAIMS, to ensure inter-laboratory comparability.

PLoS One, 2012

Insulin resistance, the key defect in type 2 diabetes (T2D), is associated with a low capacity to... more Insulin resistance, the key defect in type 2 diabetes (T2D), is associated with a low capacity to adapt fuel oxidation to fuel availability, i.e., metabolic inflexibility. This, in turn, contributes to a further damage of insulin signaling. Effectiveness of T2D treatment depends in large part on the improvement of insulin sensitivity and metabolic adaptability of the muscle, the main site of whole-body glucose utilization. We have shown previously in mice fed an obesogenic high-fat diet that a combined use of n-3 long-chain polyunsaturated fatty acids (n-3 LC-PUFA) and thiazolidinediones (TZDs), anti-diabetic drugs, preserved metabolic health and synergistically improved muscle insulin sensitivity. We investigated here whether n-3 LC-PUFA could elicit additive beneficial effects on metabolic flexibility when combined with a TZD drug rosiglitazone. Adult male C57BL/6N mice were fed an obesogenic corn oil-based high-fat diet (cHF) for 8 weeks, or randomly assigned to various interventions: cHF with n-3 LC-PUFA concentrate replacing 15% of dietary lipids (cHF+F), cHF with 10 mg rosiglitazone/kg diet (cHF+ROSI), cHF+F+ROSI, or chow-fed. Indirect calorimetry demonstrated superior preservation of metabolic flexibility to carbohydrates in response to the combined intervention. Metabolomic and gene expression analyses in the muscle suggested distinct and complementary effects of the interventions, with n-3 LC-PUFA supporting complete oxidation of fatty acids in mitochondria and the combination with n-3 LC-PUFA and rosiglitazone augmenting insulin sensitivity by the modulation of branched-chain amino acid metabolism. These beneficial metabolic effects were associated with the activation of the switch between glycolytic and oxidative muscle fibers, especially in the cHF+F+ROSI mice. Our results further support the idea that the combined use of n-3 LC-PUFA and TZDs could improve the efficacy of the therapy of obese and diabetic patients.

FEBS letters, 2005

The mechanisms controlling fat depot-specific metabolism are poorly understood. During starvation... more The mechanisms controlling fat depot-specific metabolism are poorly understood. During starvation of mice, downregulation of lipogenic genes, suppression of fatty acid synthesis, and increases in lipid oxidation were all more pronounced in epididymal than in subcutaneous fat. In epididymal fat, relatively strong upregulation of uncoupling protein 2 and phosphoenolpyruvate carboxykinase genes was found. In mice maintained both at 20 and 30°C, AMP-activated protein kinase was activated in epididymal but did not change in subcutaneous fat. Our results suggest that AMPK may have a role in the different response of various fat depots to starvation.

FEBS letters, 2004

The AMP-activated protein kinase (AMPK) cascade is a sensor of cellular energy charge that promot... more The AMP-activated protein kinase (AMPK) cascade is a sensor of cellular energy charge that promotes catabolic and inhibits anabolic pathways. However, the role of AMPK in adipocytes is poorly understood. We show that transgenic expression of mitochondrial uncoupling protein 1 in white fat, which induces obesity resistance in mice, is associated with depression of cellular energy charge, activation of AMPK, downregulation of adipogenic genes, and increase in lipid oxidation. Activation of AMPK may explain the complex metabolic changes in adipose tissue of these animals and our results support a role for adipocyte AMPK in the regulation of storage of body fat.

Genes & nutrition, 2012

Experimental replication is fundamental for practicing science. To reduce variability, it is esse... more Experimental replication is fundamental for practicing science. To reduce variability, it is essential to control sources of variation as much as possible. Diet is an important factor that can influence many processes and functional outcomes in studies performed with rodent models. This is especially true for, but not limited to, nutritional studies. To compare functional effects of different nutrients, it is important to use standardized, semi-purified diets. Here, we propose and describe a standard reference diet, the BIOCLAIMS standard diet. The diet is AIN-93 based, but further defined with dietary and experimental requirements taken into account that allow for experiments with bioactive food components and natural (non-expensive) labeling. This diet will be implemented by two European research consortia, Mitofood and BIOCLAIMS, to ensure inter-laboratory comparability.

PLoS One, 2012

Insulin resistance, the key defect in type 2 diabetes (T2D), is associated with a low capacity to... more Insulin resistance, the key defect in type 2 diabetes (T2D), is associated with a low capacity to adapt fuel oxidation to fuel availability, i.e., metabolic inflexibility. This, in turn, contributes to a further damage of insulin signaling. Effectiveness of T2D treatment depends in large part on the improvement of insulin sensitivity and metabolic adaptability of the muscle, the main site of whole-body glucose utilization. We have shown previously in mice fed an obesogenic high-fat diet that a combined use of n-3 long-chain polyunsaturated fatty acids (n-3 LC-PUFA) and thiazolidinediones (TZDs), anti-diabetic drugs, preserved metabolic health and synergistically improved muscle insulin sensitivity. We investigated here whether n-3 LC-PUFA could elicit additive beneficial effects on metabolic flexibility when combined with a TZD drug rosiglitazone. Adult male C57BL/6N mice were fed an obesogenic corn oil-based high-fat diet (cHF) for 8 weeks, or randomly assigned to various interventions: cHF with n-3 LC-PUFA concentrate replacing 15% of dietary lipids (cHF+F), cHF with 10 mg rosiglitazone/kg diet (cHF+ROSI), cHF+F+ROSI, or chow-fed. Indirect calorimetry demonstrated superior preservation of metabolic flexibility to carbohydrates in response to the combined intervention. Metabolomic and gene expression analyses in the muscle suggested distinct and complementary effects of the interventions, with n-3 LC-PUFA supporting complete oxidation of fatty acids in mitochondria and the combination with n-3 LC-PUFA and rosiglitazone augmenting insulin sensitivity by the modulation of branched-chain amino acid metabolism. These beneficial metabolic effects were associated with the activation of the switch between glycolytic and oxidative muscle fibers, especially in the cHF+F+ROSI mice. Our results further support the idea that the combined use of n-3 LC-PUFA and TZDs could improve the efficacy of the therapy of obese and diabetic patients.

FEBS letters, 2005

The mechanisms controlling fat depot-specific metabolism are poorly understood. During starvation... more The mechanisms controlling fat depot-specific metabolism are poorly understood. During starvation of mice, downregulation of lipogenic genes, suppression of fatty acid synthesis, and increases in lipid oxidation were all more pronounced in epididymal than in subcutaneous fat. In epididymal fat, relatively strong upregulation of uncoupling protein 2 and phosphoenolpyruvate carboxykinase genes was found. In mice maintained both at 20 and 30°C, AMP-activated protein kinase was activated in epididymal but did not change in subcutaneous fat. Our results suggest that AMPK may have a role in the different response of various fat depots to starvation.