Association of Mitochondrial Dysfunction with Oxidative Stress and Immune Suppression in Blunt Snout Bream Megalobrama amblycephala Fed a High‐Fat Diet

Abstract

High-fat diets may have favorable effects on growth, partly based on protein sparing, but high-fat diets often lead to fatty liver (excessive fat deposition in the liver), which may be deleterious to fish growth and health. The goal of this study was therefore to investigate possible adverse effects and how they develop. Juvenile Blunt Snout Bream Megalobrama amblycephala (initial weight ± SE = 17.70 ± 0.10 g) were fed two diets (5% fat [control] or 15% fat). After 8 weeks, fish that were fed the 15% fat diet showed a high rate of mortality and poor growth. The histological results clearly showed that the high fat intake resulted in fat and glycogen accumulation and structural alterations of the hepatocytes, mitochondria, and nuclei. In the high-fat group, impairments of the mitochondria included mitochondrial swelling and the loss of cristae and matrix. Fish that were given the 15% fat diet exhibited low succinate dehydrogenase and Na(+),K(+)-ATPase activities and increased cytochrome-c release from the mitochondria. Expression of genes for complex I and III subunits of the mitochondrial respiratory chain were down-regulated in fish that received the high-fat diet. Increases in malondialdehyde level and the ratio of oxidized glutathione to reduced glutathione suggested oxidative stress in the livers of fish from the high-fat diet group. Moreover, the lower leukocyte count, lysozyme and alternative complement activities, and globulin level in fish that received the high-fat diet indicated suppressive immune responses. Overall, the intake of excessive fat impaired mitochondrial bioenergetics and physiological functions. The dysfunction of the mitochondria subsequently mediated oxidative stress and hepatocyte apoptosis, which in turn led to the reduced efficacy of the immune system.

Effects of high-fat diets on growth performance, endoplasmic reticulum stress and mitochondrial damage in blunt snout breamMegalobrama amblycephala

“…This indicated that a long‐term intake of high‐fat diets could enhance lipogenesis but inhibit lipolysis. Those results were in accordance with previous studies on this species (Lu, Xu, Liu, et al, ; Lu, Xu, Wang, et al, ; Xu et al, ). This result may be explained by two assumptions: (a) SREBP1, a key transcriptional factor involved in lipogenesis (Spiegelman & Flier, ), mediated TG synthesis by the regulation of genes involved in lipogenesis and lipid storage, mainly in the liver (Horton, Goldstein, & Brown, ), such as ACCα which is closely involved in FA biosynthesis (Castro et al, ).…”

“…In addition, an increase in cytochrome c in the cytosol of fish from the high‐fat diet group was indicative of cytochrome c release from the mitochondria, indicating a change in the permeability of the mitochondrial membrane. Those data were in accordance with previous studies on this species (Lu, Xu, Liu, et al, ). However, simvastatin supplementation reduced cytochrome c content in the cytoplasm of blunt snout bream fed high‐fat diet.…”

“…However, in some fish species, the pros and cons of increasing the level of fat in the feed must be evaluated very carefully (Du et al, ). In fact, increasing dietary lipid levels within a certain range will support higher growth rates for fish (Lu, Xu, Liu, et al, ). However, administration of a high‐fat diet near the upper limit often results in the deposition of unwanted fat in the liver inducing a condition known as fatty liver disease (FLD) (Du et al, ; Lu et al, ).…”

Effects of dietary lipid levels on growth, fatty acid composition, antioxidant status and lipid metabolism in juvenileOnychostoma macrolepis

“…In the recent years, there has been a tendency of utilizing lipid‐rich diets in intensive aquaculture, because higher growth rates can be achieved by increasing dietary lipids above their minimum levels, probably as a result of protein sparing and improved feeding efficiency (Boujard et al, ; Lu et al, ). However, there will also be an upper limit that, if exceeded, will result in unwanted deposition of lipids in the tissues due to an imbalance of nutrient and energy supplies, and may negatively affect survival, growth, disease resistance, stress response and lipid metabolism (Chen et al, ; Company, Calduch‐Giner, Kaushik, & Perez‐Sanchez, ; Gaylord & Gatlin, ; Li et al, ; Lu et al, ; Regost et al, ; Wang et al, ).…”

Optimal dietary carbohydrate to lipid ratio for bullfrog Rana (Lithobates) catesbeiana

“…In addition, liver lipid of bullfrog fed the CHO/L 1.82 and 1.20 diets were significantly higher than that of other groups. It is reported that dietary lipid toward an upper limit often leads unwanted deposition in the liver referred as fatty liver, inducing anomalies of metabolism and physical properties (Rueda‐Jasso, Conceição, Dias, Coen, Gomes, Rees, Soares, Dinis & Sorgeloos ; Lu, Xu, Li, Li, Huang & Liu ; Lu, Xu, Liu, Wang, Zhang & Li ).…”