Non-alcoholic fatty liver disease (NAFLD) is a common disease that causes serious liver damage. Exercise is recognized as a non-pharmacological tool to improve the pathology of NAFLD. However, the antioxidative effects and mechanisms by which exercise ameliorates NAFLD remain unclear. The present study conducted exercise training on zebrafish during a 12-week high-fat feeding period to study the antioxidant effect of exercise on the liver. We found that swimming exercise decreased lipid accumulation and improved pathological changes in the liver of high-fat diet-fed zebrafish. Moreover, swimming alleviated NOX4-derived reactive oxygen species (ROS) overproduction and reduced methanedicarboxylic aldehyde (MDA) levels. We also examined the anti-apoptotic effects of swimming and found that it increased the expression of antiapoptotic factor bcl2 and decreased the expression of genes associated with apoptosis (caspase3, bax). Mechanistically, swimming intervention activated SIRT1/AMPK signaling-mediated lipid metabolism and inflammation as well as enhanced AKT and NRF2 activation and upregulated downstream antioxidant genes. In summary, exercise attenuates pathological changes in the liver induced by high-fat diets. The underlying mechanisms might be related to NRF2 and mediated by SIRT1/AMPK signaling.

Sarcopenia is a common skeletal muscle degenerative disease characterized by decreased skeletal muscle mass and mitochondrial dysfunction that involves microRNAs (miR) as regulatory factors in various pathways. Exercise reduces age-related oxidative damage and chronic inflammation and increases autophagy, among others. Moreover, whether aerobic exercise can regulate mitochondrial homeostasis by modulating the miR-128/insulin-like growth factor-1 (IGF-1) signaling pathway and can improve sarcopenia requires further investigation. Interestingly, zebrafish have been used as a model for aging research for over a decade due to their many outstanding advantages. Therefore, we established a model of zebrafish sarcopenia using d-galactose immersion and observed substantial changes, including reduced skeletal muscle cross-sectional area, increased tissue fibrosis, decreased motility, increased skeletal muscle reactive oxygen species, and notable alterations in mitochondrial morphology and function. We found that miR-128 expression was considerably upregulated, where as Igf1 and peroxisome proliferator-activated receptor gamma coactivator 1-alpha were significantly downregulated; moreover, mitochondrial homeostasis was reduced. Four weeks of aerobic exercise delayed sarcopenia progression and prevented the disruption of mitochondrial function and homeostasis. The genes related to atrophy and miR-128 were downregulated, Igf1 expression was considerably upregulated, and the phosphorylation levels of Pi3k, Akt, and Foxo3a were upregulated. Furthermore, mitochondrial respiration and homeostasis were enhanced. In conclusion, aerobic exercise improved skeletal muscle quality and function via the miR-128/IGF-1 signaling pathway, consequently ameliorating mitochondrial homeostasis in aging skeletal muscle.

Obesity is a highly prevalent disease that can induce metabolic syndrome and is associated with a greater risk of muscular atrophy. Mitochondria play central roles in regulating the physiological metabolism of skeletal muscle; however, whether a decreased mitochondrial function is associated with impaired muscle function is unclear. In this study, we evaluated the effects of a high-fat diet on muscle mitochondrial function in a zebrafish model of sarcopenic obesity (SOB). In SOB zebrafish, a significant decrease in exercise capacity and skeletal muscle fiber cross-sectional area was detected, accompanied by high expression of the atrophy-related markers Atrogin-1 and muscle RING-finger protein-1. Zebrafish with SOB exhibited inhibition of mitochondrial biogenesis and fatty acid oxidation as well as disruption of mitochondrial fusion and fission in atrophic muscle. Thus, our findings showed that muscle atrophy was associated with SOB-induced mitochondrial dysfunction. Overall, these results showed that the SOB zebrafish model established in this study may provide new insights into the development of therapeutic strategies to manage mitochondria-related muscular atrophy.

Introduction: Recent reports indicate that mitochondrial quality decreases during non-alcoholic fatty liver disease (NAFLD) progression, and targeting the mitochondria may be a possible treatment for NAFLD. Exercise can effectively slow NAFLD progression or treat NAFLD. However, the effect of exercise on mitochondrial quality in NAFLD has not yet been established.Methods: In the present study, we fed zebrafish a high-fat diet to model NAFLD, and subjected the zebrafish to swimming exercise.Results: After 12 weeks, swimming exercise significantly reduced high-fat diet-induced liver injury, and reduced inflammation and fibrosis markers. Swimming exercise improved mitochondrial morphology and dynamics, inducing upregulation of optic atrophy 1(OPA1), dynamin related protein 1 (DRP1), and mitofusin 2 (MFN2) protein expression. Swimming exercise also activated mitochondrial biogenesis via the sirtuin 1 (SIRT1)/ AMP-activated protein kinase (AMPK)/ PPARgamma coactivator 1 alpha (PGC1α) pathway, and improved the mRNA expression of genes related to mitochondrial fatty acid oxidation and oxidative phosphorylation. Furthermore, we find that mitophagy was suppressed in NAFLD zebrafish liver with the decreased numbers of mitophagosomes, the inhibition of PTEN-induced kinase 1 (PINK1) – parkin RBR E3 ubiquitin protein ligase (PARKIN) pathway and upregulation of sequestosome 1 (P62) expression. Notably, swimming exercise partially recovered number of mitophagosomes, which was associated with upregulated PARKIN expression and decreased p62 expression.Discussion: These results demonstrate that swimming exercise could alleviate the effects of NAFLD on the mitochondria, suggesting that exercise may be beneficial for treating NAFLD.

Congenital heart defects (CHDs) are common human birth defects. Genetic mutations potentially cause the exhibition of various pathological phenotypes associated with CHDs, occurring alone or as part of certain syndromes. Zebrafish, a model organism with a strong molecular conservation similar to humans, is commonly used in studies on cardiovascular diseases owing to its advantageous features, such as a similarity to human electrophysiology, transparent embryos and larvae for observation, and suitability for forward and reverse genetics technology, to create various economical and easily controlled zebrafish CHD models. In this review, we outline the pros and cons of zebrafish CHD models created by genetic mutations associated with single defects and syndromes and the underlying pathogenic mechanism of CHDs discovered in these models. The challenges of zebrafish CHD models generated through gene editing are also discussed, since the cardiac phenotypes resulting from a single-candidate pathological gene mutation in zebrafish might not mirror the corresponding human phenotypes. The comprehensive review of these zebrafish CHD models will facilitate the understanding of the pathogenic mechanisms of CHDs and offer new opportunities for their treatments and intervention strategies.