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The severity of rat liver injury by fructose and high fat depends on the degree of respiratory dysfunction and oxidative stress induced in mitochondria.
Lipids Health Dis. 2019 Mar 30; 18(1):78.LH

Abstract

BACKGROUND

High fat or fructose induces non-alcoholic fatty liver disease (NAFLD) accompanied of mitochondrial dysfunction and oxidative stress. Controversy remains about whether fructose or fat is more deleterious for NAFLD development. To get more insights about this issue and to determine if the severity of liver disease induced by fructose or fat is related to degree of mitochondrial dysfunction, we compared the effects of diets containing high fat (HF), fructose (Fr) or high fat plus fructose (HF + Fr) on NAFLD development, mitochondrial function, ROS production and lipid peroxidation.

METHODS

Wistar rats were assigned to four groups: Control, fed with standard rodent chow; High fat (HF), supplemented with lard and hydrogenated vegetable oil; Fructose (Fr), supplemented with 25% fructose in the drinking water; High fat plus fructose group (HF + Fr), fed with both HF and Fr diets. Rats were sacrificed after 6 weeks of diets consumption and the liver was excised for histopathological analysis by hematoxylin and eosin staining and for mitochondria isolation. Mitochondrial function was evaluated by measuring both mitochondrial respiration and complex I activity. Lipid peroxidation and ROS production were evaluated in mitochondria by the thiobarbituric acid method and with the fluorescent ROS probe 2,4-H2DCFDA, respectively.

RESULTS

Fr group underwent the lower degree of both liver damage and mitochondrial dysfunction that manifested like less than 20% of hepatocytes with microvesicular steatosis and partial decrease in state 3 respiration, respectively. HF group displayed an intermediate degree of damage as it showed 40% of hepatocytes with microvesicular steatosis and diminution of both state 3 respiration and complex I activity. HF + Fr group displayed more severe damage as showed microvesicular steatosis in 60% of hepatocytes and inflammation, while mitochondria exhibited fully inhibited state 3 respiration, impaired complex I activity and increased ROS generation. Exacerbation of mitochondrial lipid peroxidation was observed in both the Fr and HF + Fr groups.

CONCLUSION

Severity of liver injury induced by fructose or fat was related to the degree of dysfunction and oxidative damage in mitochondria. Attention should be paid on the serious effects observed in the HF + Fr group as the typical Western diet is rich in both fat and carbohydrates.

Authors+Show Affiliations

Instituto de Investigaciones Químico-Biológicas, Universidad Michoacana de San Nicolás de Hidalgo, Edificio B-3, Ciudad Universitaria, 58030, Morelia, Michoacán, Mexico.Instituto de Investigaciones Químico-Biológicas, Universidad Michoacana de San Nicolás de Hidalgo, Edificio B-3, Ciudad Universitaria, 58030, Morelia, Michoacán, Mexico.Instituto de Investigaciones Químico-Biológicas, Universidad Michoacana de San Nicolás de Hidalgo, Edificio B-3, Ciudad Universitaria, 58030, Morelia, Michoacán, Mexico.Hospital General Regional 36, Instituto Mexicano del Seguro Social - IMSS, 72090, Puebla, Puebla, Mexico.Hospital Regional de Alta Especialidad del Instituto de Seguridad y Servicios Sociales de los Trabajadores del Estado - ISSSTE, Carr. Morelia-Atapaneo Km 6, Atapaneo, 58300, Morelia, Michoacán, Mexico.Instituto de Investigaciones Químico-Biológicas, Universidad Michoacana de San Nicolás de Hidalgo, Edificio B-3, Ciudad Universitaria, 58030, Morelia, Michoacán, Mexico.Facultad de Ciencias Médicas y Biológicas "Dr. Ignacio Chávez", Universidad Michoacana de San Nicolás de Hidalgo, 58020, Morelia, Michoacán, Mexico.Instituto de Investigaciones Químico-Biológicas, Universidad Michoacana de San Nicolás de Hidalgo, Edificio B-3, Ciudad Universitaria, 58030, Morelia, Michoacán, Mexico. christiancortesrojo@gmail.com.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

30927921

Citation

García-Berumen, Claudia Isabel, et al. "The Severity of Rat Liver Injury By Fructose and High Fat Depends On the Degree of Respiratory Dysfunction and Oxidative Stress Induced in Mitochondria." Lipids in Health and Disease, vol. 18, no. 1, 2019, p. 78.
García-Berumen CI, Ortiz-Avila O, Vargas-Vargas MA, et al. The severity of rat liver injury by fructose and high fat depends on the degree of respiratory dysfunction and oxidative stress induced in mitochondria. Lipids Health Dis. 2019;18(1):78.
García-Berumen, C. I., Ortiz-Avila, O., Vargas-Vargas, M. A., Del Rosario-Tamayo, B. A., Guajardo-López, C., Saavedra-Molina, A., Rodríguez-Orozco, A. R., & Cortés-Rojo, C. (2019). The severity of rat liver injury by fructose and high fat depends on the degree of respiratory dysfunction and oxidative stress induced in mitochondria. Lipids in Health and Disease, 18(1), 78. https://doi.org/10.1186/s12944-019-1024-5
García-Berumen CI, et al. The Severity of Rat Liver Injury By Fructose and High Fat Depends On the Degree of Respiratory Dysfunction and Oxidative Stress Induced in Mitochondria. Lipids Health Dis. 2019 Mar 30;18(1):78. PubMed PMID: 30927921.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - The severity of rat liver injury by fructose and high fat depends on the degree of respiratory dysfunction and oxidative stress induced in mitochondria. AU - García-Berumen,Claudia Isabel, AU - Ortiz-Avila,Omar, AU - Vargas-Vargas,Manuel Alejandro, AU - Del Rosario-Tamayo,Bricia A, AU - Guajardo-López,Clotilde, AU - Saavedra-Molina,Alfredo, AU - Rodríguez-Orozco,Alain Raimundo, AU - Cortés-Rojo,Christian, Y1 - 2019/03/30/ PY - 2018/12/27/received PY - 2019/03/21/accepted PY - 2019/4/1/entrez PY - 2019/4/1/pubmed PY - 2019/7/28/medline KW - Complex I, lipid peroxidation KW - Mitochondria KW - NAFLD, liver steatosis KW - Respiratory chain SP - 78 EP - 78 JF - Lipids in health and disease JO - Lipids Health Dis VL - 18 IS - 1 N2 - BACKGROUND: High fat or fructose induces non-alcoholic fatty liver disease (NAFLD) accompanied of mitochondrial dysfunction and oxidative stress. Controversy remains about whether fructose or fat is more deleterious for NAFLD development. To get more insights about this issue and to determine if the severity of liver disease induced by fructose or fat is related to degree of mitochondrial dysfunction, we compared the effects of diets containing high fat (HF), fructose (Fr) or high fat plus fructose (HF + Fr) on NAFLD development, mitochondrial function, ROS production and lipid peroxidation. METHODS: Wistar rats were assigned to four groups: Control, fed with standard rodent chow; High fat (HF), supplemented with lard and hydrogenated vegetable oil; Fructose (Fr), supplemented with 25% fructose in the drinking water; High fat plus fructose group (HF + Fr), fed with both HF and Fr diets. Rats were sacrificed after 6 weeks of diets consumption and the liver was excised for histopathological analysis by hematoxylin and eosin staining and for mitochondria isolation. Mitochondrial function was evaluated by measuring both mitochondrial respiration and complex I activity. Lipid peroxidation and ROS production were evaluated in mitochondria by the thiobarbituric acid method and with the fluorescent ROS probe 2,4-H2DCFDA, respectively. RESULTS: Fr group underwent the lower degree of both liver damage and mitochondrial dysfunction that manifested like less than 20% of hepatocytes with microvesicular steatosis and partial decrease in state 3 respiration, respectively. HF group displayed an intermediate degree of damage as it showed 40% of hepatocytes with microvesicular steatosis and diminution of both state 3 respiration and complex I activity. HF + Fr group displayed more severe damage as showed microvesicular steatosis in 60% of hepatocytes and inflammation, while mitochondria exhibited fully inhibited state 3 respiration, impaired complex I activity and increased ROS generation. Exacerbation of mitochondrial lipid peroxidation was observed in both the Fr and HF + Fr groups. CONCLUSION: Severity of liver injury induced by fructose or fat was related to the degree of dysfunction and oxidative damage in mitochondria. Attention should be paid on the serious effects observed in the HF + Fr group as the typical Western diet is rich in both fat and carbohydrates. SN - 1476-511X UR - https://www.unboundmedicine.com/medline/citation/30927921/The_severity_of_rat_liver_injury_by_fructose_and_high_fat_depends_on_the_degree_of_respiratory_dysfunction_and_oxidative_stress_induced_in_mitochondria_ L2 - https://lipidworld.biomedcentral.com/articles/10.1186/s12944-019-1024-5 DB - PRIME DP - Unbound Medicine ER -