High-Lard and High-Fish-Oil Diets Differ in Their Effects on Function and Dynamic Behaviour of Rat Hepatic Mitochondria

Abstract

BackgroundMitochondria are dynamic organelles that frequently undergo fission and fusion processes, and imbalances in these processes may be involved in obesity and insulin resistance.AimsThe present work had the following aims: (a) to evaluate whether the mitochondrial dysfunction present in the hepatic steatosis induced by a high-fat diet is associated with changes in mitochondrial dynamics and morphology; (b) to evaluate whether effects on the above parameters differ between high-lard and high-fish-oil diets, as it has been suggested that fish oil may have anti-obesity and anti-steatotic effects by stimulating fatty acids utilisation.MethodsThe development of hepatic steatosis and insulin resistance was monitored in rats fed a high-lard or high-fish-oil diet. Immunohistochemical and electronic microscopic observations were performed on liver sections. In isolated liver mitochondria, assessments of fatty acids oxidation rate, proton conductance and oxidative stress (by measuring H2O2 release and aconitase activity) were performed. Western blot and immunohistochemical analyses were performed to evaluate the presence of proteins involved in mitochondrial dynamics (i.e., fusion and fission processes). To investigate the fusion process, mitofusin 2 and autosomal dominant optic atrophy-1 (OPA1) were analysed. To investigate the fission process, the presence of dynamin-related protein 1 (Drp1) and fission 1 protein (Fis1) was assessed.ResultsHigh-lard feeding elicited greater hepatic lipid accumulation, insulin resistance with associated mitochondrial dysfunction, greater oxidative stress and a shift towards mitochondrial fission processes (versus high-fish-oil feeding, which had an anti-steatotic effect associated with increased mitochondrial fusion processes).ConclusionsDifferent types of high-fat diets differ in their effect on mitochondrial function and dynamic behaviour, leading to different cellular adaptations to over-feeding.

Mitochondrial fusion/fission process involved in the improvement of catalpol on high glucose-induced hepatic mitochondrial dysfunction

“…Fis1 is a protein participating in the mitochondrial fission process. Over-expression of Fis1 induced by excess nutrients has been reported in many studies [13,47,48]. As expected, catalpol can inhibit Fis1 expression in HFD/STZ-diabetic mouse livers (Fig.…”

“…Furthermore, a reduction in mitochondrial fusion was considered to be a key risk factor in the development of obesity and insulin resistance [45]. Enhanced fission machinery has also been found in the liver of genetically obese and diet-induced obese animals [12,13]. In order to figure out the regulation mechanism of catalpol on hepatocyte mitochondrial ATP content, the expressions of genes related to these events were analyzed.…”

“…Furthermore, the idea that the disruption of mitochondrial dynamics underlies the pathogenesis of diabetic liver disease is gaining support. Enhanced fission machinery and decreased mitochondrial respiratory capacity have been found in the livers of db/db mice and high-fat diet (HFD) rats [12,13].…”

Ablation of adipose-HO-1 expression increases white fat over beige fat through inhibition of mitochondrial fusion and of PGC1α in female mice

“…Additionally, there is a mitochondrial network function that depends on signaling molecules and the relationship between mitochondrial fusion and fission. While mitochondrial fission is orchestrated by the dynamin-related protein 1 (DRP1) and the mitochondrial fission 1 (Fis1) protein [34], [35], the fusion process is controlled by the autosomal dominant optic atrophy 1 (OPA1) protein, together with the mitochondrial fusion proteins mitofusion 1 and 2 (Mfn 1 and 2), located on the mitochondrial outer membrane, [36], [37]. As HO-1/HO-2 are known regulators of mitochondrial integrity and function [38], [39], [40], [41], we hypothesized that adipose HO-1 gene is essential for increased mitochondrial fusion that may result in an increase in the beige cell population within adipose tissue or conversion of white adipose function populations and white adipose function that include expression of PGC1α levels and thermogenic genes.…”

Lard-based high-fat diet increases secretory leukocyte protease inhibitor expression and attenuates the inflammatory response of acute lung injury in endotoxemic rats

“…Under-reporting is an important bias in epidemiological studies on diet and obesity in human subjects; therefore animal models have been widely utilized for experiments on dietary obesity [10]. Lionetti et al reported that lard (40% fat J/J) aggravated liver injury as indicated by increased hepatic TNF-a and infiltration of inflammatory cells compared with fish oil (40% fat J/J) in a 6 week feeding study in rats [11]. In contrast, as for the effect of high-fat diet (HFD) on the lungs in the absence of any acute injury, lard-based HFD (60 kcal% fat) did not influence inflammatory cytokines in the lung tissue after 3 weeks feeding [12], or in BALF after 9 weeks feeding [13] in mice.…”