RESUMO
Abstract This study aimed to compare the effects of diet and exercise of different intensities on antioxidant function, aortic endothelial cell function and serum lipids in NAFLD (nonalcoholic fatty liver disease) rats. Fifty Sprague-Dawley (SD) rats (180-220g) were randomly divided into two experimental groups and fed either a standard rodent chow diet (CON; n=10) or a high-fat diet (HFD; n=40). After 16 weeks, the animals that received the HFD were randomly separated into a high-fat control group (HFC; n=10) or three exercise training groups: HFD and low-intensity exercise (LE; n=10), HFD and moderate-intensity exercise (ME; n=10), and HFD and incremental intensity exercise (IE; n=10). These experimental rats keep sedentary or trained for the next six weeks. A detection kit was used to detect nitric oxide synthase (NOs), nitric oxide (NO), malondialdehyde (MDA) and other markers of aortic oxidative stress. The expression levels of endothelial nitric oxide synthase (e-NOS) and endothelin-1 (ET-1) were detected by immunohistochemistry. TC, TG, and other lipid metabolism parameters were detected by an automatic analyzer. Exercise with different intensities could improve lipid metabolism, enhance antioxidant function, reduce MDA (P<0.01), increase NO (P<0.01), and improve the expression of e-NOS and ET-1 (P<0.01) protein levels in NAFLD rats. Decreased blood lipids were exhibited in all exercise groups. Notably, the moderate-intensity exercise demonstrated more effect on increasing glutathione (GSH) contents (P<0.01) and decreased the expression of ET-1 protein levels (P<0.01). The results showed that exercise at different intensities improved lipid metabolism and enhanced anti-oxidation function. Moderate exercise could improve the function of aortic endothelial cells.
Resumen Este estudio tuvo como objetivo comparar los efectos de la dieta y el ejercicio a diferentes intensidades sobre la función antioxidante, la función de las células endoteliales aórticas y los lípidos séricos en ratas NAFLD (con enfermedad del hígado graso no alcohólico) y alimentados con una dieta estándar para roedores (CON; n = 10) o con una dieta alta en grasas (HFD; n = 40). Después de 16 semanas, los animales que recibieron HFD se separaron aleatoriamente en un grupo de control alto en grasas (HFC; n=10) o tres grupos de entrenamiento físico: HFD y ejercicio de baja intensidad (LE; n=10), HFD y ejercicio de intensidad moderada (ME; n=10), y HFD y ejercicio de intensidad incremental (IE; n=10). Estas ratas experimentales se mantuvieron sedentarias o entrenadas durante las próximas seis semanas. Se utilizó un kit de detección para determinar óxido nítrico sintetasa (NO), óxido nítrico (NO), malondialdehído (MDA) y otros marcadores de estrés oxidativo aórtico. Los niveles de expresión de la óxido nítrico sintetasa endotelial (e-NOS) y endotelina-1 (ET-1) se detectaron mediante inmunohistoquímica. El analizador automático detectó TC, TG y otros parámetros del metabolismo de los lípidos. El ejercicio con diferente intensidad mejoró el metabolismo de los lípidos, mejoró la función antioxidante, redujo la MDA (P <0,01), aumentó el NO (P <0,01) y mejoró la expresión de los niveles de proteína e-NOS y ET-1 (P <0,01) en ratas NAFLD. Se observó una disminución de los lípidos en sangre en todos los grupos de ejercicio. En particular, el ejercicio de intensidad moderada demostró un mayor efecto en el aumento del contenido de glutatión (GSH) (P<0,01) y disminuyó la expresión de los niveles de proteína ET-1 (P<0,01). Los resultados mostraron que el ejercicio a diferentes intensidades mejoró el metabolismo de los lípidos y mejoró función antioxidante. El ejercicio moderado podría mejorar la función de las células endoteliales aórticas.
RESUMO
OBJECTIVE: To investigate the impact of different-intensity exercise on lipid metabolism, oxidative stress, hepatocyte injury, and apoptosis and the related protein expression of endoplasmic reticulum stress on nonalcoholic fatty liver disease rats. METHOD: 50 male Sprague-Dawley rats, 2 months old, were randomly divided into the normal control (CON) group, high-fat diet (HFD) group, low-intensity exercise (LIE) group, moderate-intensity exercise (MIE) group, and incremental-intensity exercise (IIE) group. Blood lipids were tested by the automatic biochemical analyzer. The changes in liver tissues were observed by hematoxylin-eosin staining (HE). The protein expression of Bax and Bcl-2 was detected by the immunohistochemical method. The apoptosis of hepatocytes was detected by the TUNEL method. The protein expression of GRP78, Caspase-3, IRE1, p-IRE1, JNK1, CHOP, PERK, eIF2α, and ATF4 was detected by Western blotting. RESULTS: Our study showed that compared with the HFD group, TG, TC, FFA, and LDL-c were reduced in all exercise groups. The different exercise intensities could reduce the protein expression of ATF4, Bax, and hepatocyte apoptosis. Meanwhile, the antioxidant function and Bcl-2 were increased. However, the moderate-intensity exercise demonstrated more effect on improving the antioxidant capacity and inhibiting hepatocyte apoptosis. Compared with the HFD group, Caspase-3 and JNK were significantly decreased in all exercise groups (P < 0.01) and CHOP was decreased in the LIE and MIE groups (P < 0.05). IRE1, eIF2α, the ratio of p-IRE1/IRE1 (P < 0.01), and ATF4 were decreased (P < 0.05) in the MIE group. Compared with the IIE group, p-IRE1 was decreased (P < 0.05) in the MIE group. GRP78 had no significant difference among the exercise groups. CONCLUSION: Exercise at different intensities improved blood lipid and hepatic injury in NAFLD rats. However, the body weight of the rats in each exercise group was not significantly different. Moderate-intensity exercise demonstrated more effect on improving the antioxidant ability and inhibiting hepatocyte apoptosis. The possible mechanism depends on the regulation of endoplasmic reticulum stress signaling pathways IRE1/JNK and eIF2α/CHOP.