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Rat liver: Dexamethasone treatment vs. Control

ABSTRACT: Sixteen male Sprague-Dawley rats were randomly allocated into 2 groups (8 rats per group) as follows: the control group (CON) and the dexamethasone-treated group (DEXA). Dexamethasone-treated rats received a daily intraperitoneal injection of 1.5 mg/kg of dexamethasone for 5 days. All rats were fasted during the night following the fifth day. On the sixth day, the animals were killed by decapitation. In order to focus our investigation on metabolism-related genes, we developed a metabolism dedicated microarray tool: the Mitoligo. Using this microarray tool, we were able to determine that energy metabolism was deeply modified by dexamethasone treatment. Dexamethasone treatment to rats induces a complete switch of the metabolism toward a maximal rate of ATP synthesis. In this study, we show that substrate supplying for oxidative phosphorylation is greatly enhanced. We also confirm that oxidative phosphorylation capacity is increased by dexamethasone treatment. Keywords: hormonal treatment

ORGANISM(S): Rattus norvegicus Homo sapiens

PROVIDER: GSE9035 | GEO | 2008/01/13

SECONDARY ACCESSION(S): PRJNA102537

REPOSITORIES: GEO

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Project description:Metabolic syndrome is associated with chronic low-grade inflammation which plays an important role in the pathogenesis of insulin resistance. Salsalate is a non-steroidal anti-inflammatory drug that reduces levels of inflammatory mediators. In the current study, we tested the effects of salsalate on inflammation, oxidative stress and metabolic disturbances in an animal model of inflammation and metabolic syndrome, using spontaneously hypertensive rats that transgenically express human C-reactive protein (SHR-CRP). We treated 15-month-old male transgenic SHR-CRP rats with salsalate (200 mg/kg/day) mixed as part of a standard diet for 4 weeks. A corresponding untreated control group of male transgenic SHR-CRP rats were fed a standard diet without salsalate. In a similar fashion, we studied a group of nontransgenic SHR treated with salsalate and an untreated group of nontransgenic SHR controls. Parameters of inflammation and glucose and lipid metabolism were measured using standard methods. Statistical significance was evaluated by two-way ANOVA. In the SHR-CRP transgenic strain, we found that salsalate treatment decreased circulating levels of inflammatory markers TNFï¡ and MCP-1 and levels of human CRP as well as reduced levels of lipopreroxidation products in the liver and kidney cortex. Lipidomics analysis of eicosanoids confirmed anti-inflammatory effects of salsalate. Reduced inflammation and oxidative stress were associated with increased sensitivity of skeletal muscles to insulin action and greater tolerance to glucose and with reduced glucose oxidation and incorporation in brown adipose tissue (BAT). In SHR controls with no CRP-induced inflammation, salsalate treatment was associated with reduced body weight, lower levels of serum free fatty acids, total and HDL cholesterol and increased palmitate oxidation and incorporation in BAT. Salsalate regulated lipid metabolism by affecting expression of genes from PPAR signaling pathways and inflammation by affecting expression from MAPK signaling and NOD-like receptor signaling pathways. In summary, in the presence of high levels of human CRP, salsalate reduced inflammation which was associated with reduced oxidative stress and amelioration of insulin resistance in skeletal muscle and glucose intolerance while in non-transgenic SHR rats, salsalate ameliorated dyslipidemia and activated BAT. Thus it is possible that amelioration of insulin resistance and glucose intolerance in SHR-CRP rats treated with salsalate is due to reduced inflammation while amelioration of dyslipidemia in SHR rats treated with salsalate is due to activation of BAT. These findings suggest that salsalate has metabolic effects beyond suppressing inflammation.

Project description:Butyrate has a central function in the regulation of energy metabolism as a metabolite of bacterial fermentation. However, information on the direct impact of butyrate on peripheral organs or tissues is very limited, especially for muscle and adipose tissues. Therefore, this study evaluated the effects of intravenous sodium butyrate (SB) administration on the transcriptome of muscle and adipose tissue of pigs. Twelve crossbred barrows (Duroc × Landrace × Large White, 60 days of age) were fitted with a medical polyethylene cannula via internal jugular vein and were daily infused with 10 ml SB (200 mmol/l) or the same volume of physiological saline. After a 7-day experimental period, all pigs were slaughtered, and the longissimus dorsi muscle and dorsal subcutaneous adipose tissue were collected for holistic transcriptomic analysis. In muscle tissue, the expression of 12 oxidative phosphorylation related genes and seven glycolysis related genes were downregulated. Furthermore, the mRNA expression of fatty acid synthase (FASN) and stearyl coenzyme A desaturase (SCD) were significantly upregulated by SB treatment. This indicates a decrease in oxidative phosphorylation and glucose catabolism, and an increase in fat synthesis. In adipose tissue, the expressions of seven oxidative phosphorylation-related genes were downregulated, while nine glucose metabolism related genes were upregulated. Moreover, the mRNA expressions of FASN and peroxisome proliferator-activated receptor gamma (PPARγ) were upregulated, while fatty acid binding protein 3 (FABP3) and acyl-CoA synthetase long-chain family member 1 (ACSL1) were downregulated in the SB group. This indicates a decrease in oxidative phosphorylation and an increase in glucose metabolism and fat synthesis. The results suggest that short-term intravenous SB infusion can modulate muscle and adipose tissue metabolism at the transcriptional level by decreasing both oxidative phosphorylation and fat synthesis. In addition, intravenous SB decreases the glucose catabolism in muscle tissue and increases the glucose catabolism in adipose tissue. This suggests that systemic butyrate may display discriminative metabolic regulation in different tissues of barrows.

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Rat liver: Dexamethasone treatment vs. Control

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