Background: Changes in liver fatty acid desaturase activities were proposed as major factors involved in the development and progression of liver steatosis. The aim of this study was to investigate the modifications in liver fatty acid delta-9, delta-6 and delta-5 desaturase (D9D, D6D and D5D, respectively) in two rat models of NAFLD such as the methionine and choline deficient (MCD) diet model and Obese Zucker rats. Methods: Eight-week-old male Wistar rats fed for 3-week with MCD diet and relative control diet were used as nutritional model of NAFLD. Twelve-week-old Obese and Lean male Zucker rats were used as genetic model of NAFLD. Serum levels of hepatic enzymes (AST, ALT, Alkaline Phosphatase) were quantified. Hepatic TBARS and ROS were evaluated as index of oxidative stress. Liver fatty acid profiling was performed by Gas Chromatography-Mass Spectrometry analysis (GC-MS). The estimated desaturase activities were calculated using ratios of 16:1n-7/16:0 (D9-16D), 18:1n-9/18:0 (D9-18D), 18:3n-6/18:2n-6 (D6D) and 20:4n-6/20:3n-6 (D5D). The anti-inflammatory fatty acid index (AIFAI) was also quantified. Results: Liver D9-18D activity increased both in MCD and Obese Zucker rats but it was considerably upregulated in MCD rats. No changes in D9-16D occurred in MCD group while an increase was found in Obese Zucker rats. Four and two fold decrease in hepatic D-5D activity occurred in MCD and Obese Zucker rats, respectively. A comparable trend occurred for Delta-6D in MCD rats that correlated with oxidative stress assessed by TBARS and ROS (r=0.74, P<0.01 and r=0.87, P<0.001, respectively). Conversely, no D-6D was detectable in Obese Zucker rats. Liver docosahexaenoic acid (DHA; 22:6n-3) and AIFAI were lower in MCD when compared with Obese Zucker rats. No significant difference in serum AST, ALT and Alkaline Phosphatase were found comparing the two NAFLD animal models. Conclusion: Extensive changes in D9-18D, D6D and D5D occurred in MCD rats when compared with Obese Zucker rats. These events were associated with marked oxidative stress and decrease in AIFAI and DHA, this last recently found to protect against the progression to steatohepatitis that spontaneously occurs only in MCD rats. These results may contribute to the understanding of NAFLD progression and provide the basis for the identification of potential therapeutic targets able to counteract this common disorder.
Changes in liver fatty acid delta-9, delta-6 and delta-5 desaturase activities in two animal models of hepatic steatosis
Croce AC;
2018
Abstract
Background: Changes in liver fatty acid desaturase activities were proposed as major factors involved in the development and progression of liver steatosis. The aim of this study was to investigate the modifications in liver fatty acid delta-9, delta-6 and delta-5 desaturase (D9D, D6D and D5D, respectively) in two rat models of NAFLD such as the methionine and choline deficient (MCD) diet model and Obese Zucker rats. Methods: Eight-week-old male Wistar rats fed for 3-week with MCD diet and relative control diet were used as nutritional model of NAFLD. Twelve-week-old Obese and Lean male Zucker rats were used as genetic model of NAFLD. Serum levels of hepatic enzymes (AST, ALT, Alkaline Phosphatase) were quantified. Hepatic TBARS and ROS were evaluated as index of oxidative stress. Liver fatty acid profiling was performed by Gas Chromatography-Mass Spectrometry analysis (GC-MS). The estimated desaturase activities were calculated using ratios of 16:1n-7/16:0 (D9-16D), 18:1n-9/18:0 (D9-18D), 18:3n-6/18:2n-6 (D6D) and 20:4n-6/20:3n-6 (D5D). The anti-inflammatory fatty acid index (AIFAI) was also quantified. Results: Liver D9-18D activity increased both in MCD and Obese Zucker rats but it was considerably upregulated in MCD rats. No changes in D9-16D occurred in MCD group while an increase was found in Obese Zucker rats. Four and two fold decrease in hepatic D-5D activity occurred in MCD and Obese Zucker rats, respectively. A comparable trend occurred for Delta-6D in MCD rats that correlated with oxidative stress assessed by TBARS and ROS (r=0.74, P<0.01 and r=0.87, P<0.001, respectively). Conversely, no D-6D was detectable in Obese Zucker rats. Liver docosahexaenoic acid (DHA; 22:6n-3) and AIFAI were lower in MCD when compared with Obese Zucker rats. No significant difference in serum AST, ALT and Alkaline Phosphatase were found comparing the two NAFLD animal models. Conclusion: Extensive changes in D9-18D, D6D and D5D occurred in MCD rats when compared with Obese Zucker rats. These events were associated with marked oxidative stress and decrease in AIFAI and DHA, this last recently found to protect against the progression to steatohepatitis that spontaneously occurs only in MCD rats. These results may contribute to the understanding of NAFLD progression and provide the basis for the identification of potential therapeutic targets able to counteract this common disorder.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
