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-H 2 DCFDA, 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.

Hyperglycemia and mitochondrial ROS overproduction have been identified as key factors involved in the development of diabetic nephropathy. This has encouraged the search for strategies decreasing glucose levels and long-term improvement of redox status of glutathione, the main antioxidant counteracting mitochondrial damage. Previously, we have shown that avocado oil improves redox status of glutathione in liver and brain mitochondria from streptozotocin-induced diabetic rats; however, the long-term effects of avocado oil and its hypoglycemic effect cannot be evaluated because this model displays low survival and insulin depletion. Therefore, we tested during 1 year the effects of avocado oil on glycemia, ROS levels, lipid peroxidation and glutathione status in kidney mitochondria from type 2 diabetic Goto-Kakizaki rats. Diabetic rats exhibited glycemia of 120-186 mg/dL the first 9 months with a further increase to 250-300 mg/dL. Avocado oil decreased hyperglycemia at intermediate levels between diabetic and control rats. Diabetic rats displayed augmented lipid peroxidation and depletion of reduced glutathione throughout the study, while increased ROS generation was observed at the 3rd and 12th months along with diminished content of total glutathione at the 6th and 12th months. Avocado oil ameliorated all these defects and augmented the mitochondrial content of oleic acid. The beneficial effects of avocado oil are discussed in terms of the hypoglycemic effect of oleic acid and the probable dependence of glutathione transport on lipid peroxidation and thiol oxidation of mitochondrial carriers.

Hypertension impairs the function of the kidney and its vasculature. Adrenergic activation is involved in these processes by promoting oxidative stress and mitochondrial dysfunction. Thus, the targeting of mitochondrial function and mitochondrial oxidative stress may be an approach to alleviate hypertensive kidney damage. Avocado oil, a source of oleic acid and antioxidants, improves mitochondrial dysfunction, decreases mitochondrial oxidative stress, and enhances vascular function in hypertensive rats. However, whether avocado oil improves the function of renal vasculature during the adrenergic stimulation, and if this is related to improvement in renal damage and enhancement of mitochondrial activity is unknown. Thus, the effects of avocado oil on renal vascular responses to adrenergic stimulation, mitochondrial dysfunction, oxidative stress, and renal damage were compared with prazosin, an antagonist of α1-adrenoceptors, in hypertensive rats induced by L-NAME. Avocado oil or prazosin decreased blood pressure, improved endothelium—dependent renal vasodilation, prevented mitochondrial dysfunction and kidney damage in hypertensive rats. However, avocado oil, but not prazosin, decreased mitochondrial ROS generation and improved the redox state of mitochondrial glutathione. These results suggest that avocado oil and prazosin prevented hypertensive renal damage due to the improvement in mitochondrial function.

Nonalcoholic Fatty Liver Disease (NAFLD) is a chronic disease characterized by excessive fat accumulation, inflammation and liver dysfunction in the absence of significant alcohol consumption and without any other liver disease. NAFLD is accompanied by mitochondrial dysfunctions such as decreased activity of the enzymes of the electron transport chain (ETC), impaired β‐oxidation of fatty acids, excessive reactive oxygen species (ROS) production and increased lipid peroxidation. These last two processes have been involved in liver inflammation by augmenting the activity of cytokines like TNF‐α, and IL‐6. Mitochondrial dynamics, a process that modulates both mitochondrial morphology and function by events of fusion and fission, also becomes impaired during NAFLD by exacerbating mitochondria fission. Previously, we have reported that avocado oil, a rich source of C18:1, bioactive sterols and antioxidants, attenuates both mitochondrial dysfunctions and oxidative stress during diabetes and hypertension. Therefore, we aimed to test if avocado oil attenuates NAFLD by counteracting the alterations in both cytokines levels and mitochondrial dynamics in rats feed with a diet with high fat and fructose for 4 months. This diet led to hepatic alterations including inflammation, ballooning, necrosis and increased expression of both TNF‐α and IL‐6. Increased levels of ROS production and lipid peroxidation were observed in mitochondria, along with augmented expression of DRP1 and Fis1, two proteins of fission, and decreased levels of fusion proteins Mfn1/2 and OPA1. All these effects were counteracted when avocado oil was supplemented daily after one month of the beginning of the diet up to the end of the experiment. These data suggest that avocado oil ameliorates NAFLD by decreasing inflammation and improving mitochondrial dynamics. Thus, avocado oil may be a nutritional approach to complement pharmacological treatment of NAFLD.Support or Funding InformationThis work was supported by a Coordinación de la Investigación Científica‐UMSNH grant (to CCR)This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

Hypertension (HT) has been associated with mitochondrial dysfunction due to both nitrosative and oxidative stresses that are generated by increased activity of NADPH oxidase (Nox), defective calcium transport and enhanced ROS generation by reverse electron transfer (RET) at complex I. These factors contribute to the pathogenesis of endothelial dysfunction and to the progress of hypertensive complications. Previously, we have shown that avocado oil, a rich source of bioactive compounds and antioxidants, decreases blood pressure and ameliorates both mitochondrial dysfunction and oxidative stress in kidney from hypertensive rats. However, it is unknown whether the effects of avocado oil on renal mitochondria are attributable to decreased activity of NADPH oxidase, lowered levels of reactive nitrogen species (RNS) and improved calcium uptake by mitochondria. Thus, we analyzed Nox activity and peroxynitrite (ONOO‐) levels in kidney cytosolic fractions of L‐NAME – induced hypertensive rats as well as mitochondrial calcium uptake and complex I activity. After 60‐days of L‐NAME administration, the hypertensive rats exhibited enhanced Nox activity and ONOO‐ levels, as well as increased complex I activity and excessive calcium uptake. All these alterations were prevented by co‐administration of L‐NAME with avocado oil. Moreover, the kidneys from hypertensive rats shown histological manifestations of renal damage that were also corrected by avocado oil. These data suggest that avocado oil could be beneficial to decrease hypertensive nephropathy progression by improving mitochondrial function, diminishing RNS production and normalizing Nox activity.Support or Funding InformationThis work was supported by a Coordinación de la Investigación Científica‐UMSNH grant (to CCR)This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.