Mitochondrial Nutrients Research Articles

Mitochondrial dysfunction in Fragile X syndrome and Fragile X-associated tremor/ataxia syndrome: prospect use of antioxidants and mitochondrial nutrients

Fragile X syndrome (FXS) is a genetic disorder characterized by mutation in the FMR1 gene, leading to the absence or reduced levels of fragile X Messenger Ribonucleoprotein 1 (FMRP). This results in neurodevelopmental deficits, including autistic spectrum conditions. On the other hand, Fragile X-associated tremor/ataxia syndrome (FXTAS) is a distinct disorder caused by the premutation in the FMR1 gene. FXTAS is associated with elevated levels of FMR1 mRNA, leading to neurodegenerative manifestations such as tremors and ataxia.Mounting evidence suggests a link between both syndromes and mitochondrial dysfunction (MDF). In this minireview, we critically examine the intricate relationship between FXS, FXTAS, and MDF, focusing on potential therapeutic avenues to counteract or mitigate their adverse effects. Specifically, we explore the role of mitochondrial cofactors and antioxidants, with a particular emphasis on alpha-lipoic acid (ALA), carnitine (CARN) and Coenzyme Q10 (CoQ10). Findings from this review will contribute to a deeper understanding of these disorders and foster novel therapeutic strategies to enhance patient outcomes.

Mitonuclear interactions shape both direct and parental effects of diet on fitness and involve a SNP in mitoribosomal 16s rRNA.

Nutrition is a primary determinant of health, but responses to nutrition vary with genotype. Epistasis between mitochondrial and nuclear genomes may cause some of this variation, but which mitochondrial loci and nutrients participate in complex gene-by-gene-by-diet interactions? Furthermore, it remains unknown whether mitonuclear epistasis is involved only in the immediate responses to changes in diet, or whether mitonuclear genotype might modulate sensitivity to variation in parental nutrition, to shape intergenerational fitness responses. Here, in Drosophila melanogaster, we show that mitonuclear epistasis shapes fitness responses to variation in dietary lipids and amino acids. We also show that mitonuclear genotype modulates the parental effect of dietary lipid and amino acid variation on offspring fitness. Effect sizes for the interactions between diet, mitogenotype, and nucleogenotype were equal to or greater than the main effect of diet for some traits, suggesting that dietary impacts cannot be understood without first accounting for these interactions. Associating phenotype to mtDNA variation in a subset of populations implicated a C/T polymorphism in mt:lrRNA, which encodes the 16S rRNA of the mitochondrial ribosome. This association suggests that directionally different responses to dietary changes can result from variants on mtDNA that do not change protein coding sequence, dependent on epistatic interactions with variation in the nuclear genome.

S-Glutathionylation and S-Nitrosylation in Mitochondria: Focus on Homeostasis and Neurodegenerative Diseases.

Redox post-translational modifications are derived from fluctuations in the redox potential and modulate protein function, localization, activity and structure. Amongst the oxidative reversible modifications, the S-glutathionylation of proteins was the first to be characterized as a post-translational modification, which primarily protects proteins from irreversible oxidation. However, a growing body of evidence suggests that S-glutathionylation plays a key role in core cell processes, particularly in mitochondria, which are the main source of reactive oxygen species. S-nitrosylation, another post-translational modification, was identified >150 years ago, but it was re-introduced as a prototype cell-signaling mechanism only recently, one that tightly regulates core processes within the cell’s sub-compartments, especially in mitochondria. S-glutathionylation and S-nitrosylation are modulated by fluctuations in reactive oxygen and nitrogen species and, in turn, orchestrate mitochondrial bioenergetics machinery, morphology, nutrients metabolism and apoptosis. In many neurodegenerative disorders, mitochondria dysfunction and oxidative/nitrosative stresses trigger or exacerbate their pathologies. Despite the substantial amount of research for most of these disorders, there are no successful treatments, while antioxidant supplementation failed in the majority of clinical trials. Herein, we discuss how S-glutathionylation and S-nitrosylation interfere in mitochondrial homeostasis and how the deregulation of these modifications is associated with Alzheimer’s, Parkinson’s, amyotrophic lateral sclerosis and Friedreich’s ataxia.

Coenzyme Q10 + alpha lipoic acid for chronic COVID syndrome.

Chronic COVID syndrome is characterized by chronic fatigue, myalgia, depression and sleep disturbances, similar to chronic fatigue syndrome (CFS) and fibromyalgia syndrome. Implementations of mitochondrial nutrients (MNs) with diet are important for the clinical effects antioxidant. We examined if use of an association of coenzyme Q10 and alpha lipoic acid (Requpero®) could reduce chronic covid symptoms. The Requpero study is a prospective observational study in which 174 patients, who had developed chronic-covid syndrome, were divided in two groups: The first one (116 patients) received coenzyme Q10 + alpha lipoic acid, and the second one (58 patients) did not receive any treatment. Primary outcome was reduction in Fatigue Severity Scale (FSS) in treatment group compared with control group. complete FSS response was reached most frequently in treatment group than in control group. A FSS complete response was reached in 62 (53.5%) patients in treatment group and in two (3.5%) patients in control group. A reduction in FSS core < 20% from baseline at T1 (non-response) was observed in 11 patients in the treatment group (9.5%) and in 15 patients in the control group (25.9%) (p < 0.0001). To date, this is the first study that tests the efficacy of coenzyme Q10 and alpha lipoic acid in chronic Covid syndrome. Primary and secondary outcomes were met. These results have to be confirmed through a double blind placebo controlled trial of longer duration.

Dapagliflozin Attenuates Severity of Atherosclerosis through Manufacturing Energy-Crisis to Inhibit Ferroptosis of Macrophage

Background: Atherosclerosis is a main potential pathology of most cardiovascular diseases. Growing evidence has indicated that dysregulation of ferroptosis is associated with atherosclerosis. Dapagliflozinas a sodiumglucose cotransporter 2 inhibitor (SGLT2i), in view of the clinically important benefits of the sodium-glucose cotransporter 2 inhibitor (SGLT2i) dapagliflozin in improving cardiovascular outcomes, we aimed to explore its pharmacological effects and underlying mechanisms of atherosclerosis associated with ferroptosis. Method: Ferroptosis and severity of atherosclerosis were assessed in ApoE-/-(control) and ApoE-/-+Dapagliflozin (SGLT2i) mice groups to analyze the changes after Dapagliflozin treatment. ApoE-/-+Dapagliflozin+RSL3 (RSL3) mice group was established to confirm the association between ferroptosis and severity of atherosclerosis. Metabolism of nutrients and energetic phenotype of macrophages sorted by FACS within atherosclerosis plaques were analyzed to explore the mechanism of Dapagliflozin attenuating the severity of atherosclerosis. Result: Alleviated severity of atherosclerosis and ferroptosis were observed in Dapagliflozin treatment mice group, however, RSL3 treatment mice group revoke the beneficial effect. The metabolism of macrophages sorted by Fluorescence Activated Cell Sorter (FACS) with in atherosclerosis plaques indicated that Dapagliflozin treatment weakened fuel flexibility between mitochondrial respiration and nutrients consumption which leads to energy crisis within macrophages. The energy crisis mitigates ferroptosis and keeps more M2 macrophages surviving in atherosclerotic plaques. Conclusion: Dapagliflozin treatments modulate atherosclerotic plaque progression and maintain plaque stabilization by the way of creating energy crisis. Energy crisis keeps more M2 macrophages surviving in atherosclerotic plaque which is more sensitive to ferroptosis than M1 to attenuate severity of atherosclerosis. The pharmacological effects of Dapagliflozin might be a potential new therapeutic medication target for atherosclerosis lesions.

Mitigating the pro-oxidant state and melanogenesis of Retinitis pigmentosa: by counteracting mitochondrial dysfunction.

Retinitis pigmentosa (RP) is a group of mitochondrial diseases characterized by progressive degeneration of rods and cones leading to retinal loss of light sensitivity and, consequently, to blindness. To date, no cure is available according to the clinical literature. As a disease associated with pigmentation-related, pro-oxidant state, and mitochondrial dysfunction, RP may be viewed at the crossroads of different pathogenetic pathways involved in adverse health outcomes, where mitochondria play a preeminent role. RP has been investigated in a number of experimental and clinical studies aimed at delaying retinal hyperpigmentation by means of a number of natural and synthetic antioxidants, as well as mitochondrial cofactors, also termed mitochondrial nutrients (MNs), such as alpha-lipoic acid, coenzyme Q10 and carnitine. One should consider that each MN plays distinct-and indispensable-roles in mitochondrial function. Thus, a logical choice would imply the administration of MN combinations, instead of individual MNs, as performed in previous studies, and with limited, if any, positive outcomes. A rational study design aimed at comparing the protective effects of MNs, separately or in combinations, and in association with other antioxidants, might foresee the utilization of animal RP models. The results should verify a comparative optimization in preventing or effectively contrasting retinal oxidative stress in mouse RP models and, in prospect, in human RP cases.

Understanding oocyte ageing: can we influence the process as clinicians?

Oocyte quality is rate-limiting for pregnancy success and declines with age. Here, I review animal-study evidence showing dramatic reversal of oocyte ageing with mitochondrial nutrients and explore clinical evidence related to their usage. Oocyte ageing is strongly tied to mitochondrial dysfunction and oxidative stress. Quality-defining events occur over a protracted period (2-3 months in humans) when oocyte volume increases over 100-fold. Treating mice during the growth phase with mitochondrial modifiers such as CoQ10 combats oocyte ageing. Exciting new work shows that raising oocyte NAD+ levels also dramatically rejuvenate aged oocytes. However, evidence that any of these agents can reproducibly improve quality in humans is lacking. This is largely because there has been a focus on patients with poor ovarian response during IVF and/or low ovarian follicular pool size, rather than patients with poor oocyte quality. In addition, studies have used short-term treatment during ovarian stimulation after oocyte growth is already complete. Mitochondrial therapeutics such as NAD+-boosting used during the oocyte's growth phase markedly improve oocyte quality in mice. Evaluating them in humans should focus on patients with poor oocyte quality and utilise per-oocyte (rather than per-cycle) endpoints after adequate treatment that captures the growth phase when quality is defined.

The Effect of acetyl-L-carnitine, Alpha-lipoic Acid, and Coenzyme Q10 Combination in Preventing Anti-tuberculosis Drug-induced Hepatotoxicity: A Randomized, Double-blind, Placebo-controlled Clinical Trial.

Drug-induced liver injury (DILI) is one of the most serious adverse effects of anti-tuberculosis (TB) drugs. A suggested mechanism of this adverse effect is mitochondrial dysfunction (MDF). The purpose of this study was an evaluation of the possible preventive effects of the combination of acetyl-L-carnitine (ALCAR), alpha-lipoic acid (ALA), and coenzyme Q10 (CoQ10), as mitochondrial nutrients (MNs), against anti-TB DILI. In this clinical trial, patients who met the inclusion criteria were randomly assigned to either experimental (n = 44) or placebo (n = 43) groups. The experimental group received capsules containing CoQ10 (200 mg) + ALA (250 mg) + ALCAR (250 mg) orally twice daily for two weeks, and the placebo group received oral placebo capsules with the same interval and duration. The mean serum levels of aspartate aminotransferase (AST), alanine aminotransferase (ALT), and total bilirubin (TBil) at the end of the first and second weeks as well as the incidence of DILI during the intervention were recorded and compared between the two groups. At the end of the study, the mean serum levels of AST and ALT in the experimental group were significantly lower than the placebo group (36.27 ± 36.43 vs. 86.02 ± 97.23 and 28.41 ± 27.41 vs. 78.80 ± 118.28, respectively, P = 0.003 for both). Also, the incidence of anti-TB DILI was significantly lower in the experimental group than the placebo group (6.8% vs. 25.6%, P = 0.017). In conclusion, using the combination of ALCAR, ALA, and CoQ10 may provide an effective strategy in preventing anti-TB DILI.

Aging-Related Disorders and Mitochondrial Dysfunction: A Critical Review for Prospect Mitoprotective Strategies Based on Mitochondrial Nutrient Mixtures.

A number of aging-related disorders (ARD) have been related to oxidative stress (OS) and mitochondrial dysfunction (MDF) in a well-established body of literature. Most studies focused on cardiovascular disorders (CVD), type 2 diabetes (T2D), and neurodegenerative disorders. Counteracting OS and MDF has been envisaged to improve the clinical management of ARD, and major roles have been assigned to three mitochondrial cofactors, also termed mitochondrial nutrients (MNs), i.e., α-lipoic acid (ALA), Coenzyme Q10 (CoQ10), and carnitine (CARN). These cofactors exert essential–and distinct—roles in mitochondrial machineries, along with strong antioxidant properties. Clinical trials have mostly relied on the use of only one MN to ARD-affected patients as, e.g., in the case of CoQ10 in CVD, or of ALA in T2D, possibly with the addition of other antioxidants. Only a few clinical and pre-clinical studies reported on the administration of two MNs, with beneficial outcomes, while no available studies reported on the combined administration of three MNs. Based on the literature also from pre-clinical studies, the present review is to recommend the design of clinical trials based on combinations of the three MNs.

Central and Peripheral Metabolic Defects Contribute to the Pathogenesis of Alzheimer's Disease: Targeting Mitochondria for Diagnosis and Prevention.

Significance: Epidemiological studies indicate that metabolic disorders are associated with an increased risk for Alzheimer's disease (AD). Metabolic remodeling occurs in the central nervous system (CNS) and periphery, even in the early stages of AD. Mitochondrial dysfunction has been widely accepted as a molecular mechanism underlying metabolic disorders. Therefore, focusing on early metabolic changes, especially from the perspective of mitochondria, could be of interest for early AD diagnosis and intervention. Recent Advances: We and others have identified that the levels of several metabolites are fluctuated in the periphery before their accumulation in the CNS, which plays an important role in the pathogenesis of AD. Mitochondrial remodeling is likely one of the earliest signs of AD, linking nutritional imbalance to cognitive deficits. Notably, by improving mitochondrial function, mitochondrial nutrients efficiently rescue cellular metabolic dysfunction in the CNS and periphery in individuals with AD. Critical Issues: Peripheral metabolic disorders should be intensively explored and evaluated for the early diagnosis of AD. The circulating metabolites derived from mitochondrial remodeling represent novel potential diagnostic biomarkers for AD that are more readily detected than CNS-oriented biomarkers. Moreover, mitochondrial nutrients provide a promising approach to preventing and delaying AD progression. Future Directions: Abnormal mitochondrial metabolism in the CNS and periphery is involved in AD pathogenesis. More clinical studies provide evidence for the suitability and reliability of circulating metabolites and cytokines for the early diagnosis of AD. Targeting mitochondria to rewire cellular metabolism is a promising approach to preventing AD and ameliorating AD-related metabolic disorders.

Mitoprotective Clinical Strategies in Type 2 Diabetes and Fanconi Anemia Patients: Suggestions for Clinical Management of Mitochondrial Dysfunction.

Oxidative stress (OS) and mitochondrial dysfunction (MDF) occur in a number of disorders, and several clinical studies have attempted to counteract OS and MDF by providing adjuvant treatments against disease progression. The present review is aimed at focusing on two apparently distant diseases, namely type 2 diabetes (T2D) and a rare genetic disease, Fanconi anemia (FA). The pathogenetic links between T2D and FA include the high T2D prevalence among FA patients and the recognized evidence for OS and MDF in both disorders. This latter phenotypic/pathogenetic feature—namely MDF—may be regarded as a mechanistic ground both accounting for the clinical outcomes in both diseases, and as a premise to clinical studies aimed at counteracting MDF. In the case for T2D, the working hypothesis is raised of evaluating any in vivo decrease of mitochondrial cofactors, or mitochondrial nutrients (MNs) such as α-lipoic acid, coenzyme Q10, and l-carnitine, with possibly combined MN-based treatments. As for FA, the established knowledge of MDF, as yet only obtained from in vitro or molecular studies, prompts the requirement to ascertain in vivo MDF, and to design clinical studies aimed at utilizing MNs toward mitigating or delaying FA’s clinical progression. Altogether, this paper may contribute to building hypotheses for clinical studies in a number of OS/MDF-related diseases.

P-337 - Mitochondrial metabolic remodeling involved in the progression of Alzheimer's disease

Pathogenesis of Alzheimer's disease (AD) affects not only central nervous system, but also peripheral glucose and lipid metabolism. We recently find the hepatic mitochondrial metabolic remodeling arises at the early stage of AD. For example, we have demonstrated that early inflammation-associated factors diminish high fat diet-induced hepatic lipid deposition by inhibiting SREBP-1-mediated de novo lipogenesis in APP/PS1 mice, thus driving substrate flux to glucose production for hyperglycemia and hepatic insulin resistance. We also reveal that hepatic inflammatory factor enhances ketogenesis (hydroxybutyrate) through HMGCS2 (3-hydroxy-3- methylglutaryl-CoA synthase 2) signaling activation by p38/NF-kappa B p65. These results provide a novel peripheral metabolic remodeling and suggest a plausible early AD phenotype to diagnose AD. More importantly, we define a group of compounds targeting mitochondria and benefiting mitochondrial metabolic function as “mitochondrial nutrients”, promising agents in AD prevention and treatment.

Adaptations of Skeletal Muscle Mitochondria to Obesity, Exercise, and Polyunsaturated Fatty Acids.

Mitochondria intricately modulate their energy production through the control of mitochondrial adaptation (mitochondrial biogenesis, fusion, and/or fission) to meet energy demands. Nutrient overload may result in dysregulated mitochondrial biogenesis, morphology toward mitochondrial fragmentation, and oxidative stress in the skeletal muscle. In addition, physical activity and diet components influence mitochondrial function. Exercise may stimulate mitochondrial biogenesis and promote mitochondrial fusion/fission in the skeletal muscle. Moreover, some dietary fatty acids, such as n-3 polyunsaturated fatty acids and conjugated linoleic acid, have been identified to positively regulate mitochondrial adaptation in the skeletal muscle. This review discusses the association of mitochondrial impairments and obesity, and presents an overview of various mechanisms of which exercise training and mitochondrial nutrients promote mitochondrial function in the skeletal muscle.

Mitochondrial modifying nutrients in treating chronic fatigue syndrome: A 16-week open-label pilot study

IntroductionRecent evidence suggests that mitochondrial dysfunction may play a role in the pathophysiology of chronic fatigue syndrome (CFS). We undertook a pilot investigation of a combination of nutraceutical nutrient compounds which are involved in mitochondrial function and energy generation, to assess their efficacy in improving symptoms of CFS. An open-label design was employed as CFS is largely treatment-resistant with limited placebo-response. MethodsA 16-week open-label trial of a nutraceutical combination (primary nutrients: Coenzyme Q10, Alpha lipoic acid, Acetyl-l-carnitine, N-acetyl cysteine, B Vitamins, in addition to co-factors) was undertaken in ten patients with CFS. Fatigue symptoms, mood and general health were assessed at each 4-week time point over 16 weeks. Of the ten patients (7 female, 3 male) with a mean age of 36.3, eight completed the trial. ResultsLinear mixed model analysis demonstrated a significant improvement in fatigue symptoms across treatment period on the Chalder Fatigue Scale (p<0.001). Specific improvements were found in tiredness, weakness, feeling sleepy or drowsy, as well as in sleep, and clinician-reported symptom-improvement. No benefit was observed in mood or other functional domains. No serious adverse events were noted. ConclusionThese preliminary findings suggest that a combination nutraceutical compound of mitochondrial agents may improve CFS symptoms. Further investigation is warranted in a larger double-blind RCT.

Mitochondrial dysfunction and ovarian aging.

Mitochondria are double-membrane-bound organelles that are responsible for the generation of most of the cell's energy. Mitochondrial dysfunction has been implicated in cellular senescence in general and ovarian aging in particular. Recent studies exploited this association by studying mitochondrial DNA (mtDNA) copy number as a potential biomarker of embryo viability and the use of mitochondrial nutrients and autologous mitochondrial transfer as a potential treatment for poor ovarian function and response.

Mitochondrial Dysfunction and Oxidative Stress in Pediatric Diseases

Oxidative stress is a distinctive sign in a long series of human diseases, including metabolic, neurologic, and cancer disorders. Several studies demonstrated that the toxic effects resulting from a redox imbalance take place even during infant age. Recent literature focused in particular on the role exerted by unpaired mitochondrial function in the pathogenesis of these diseases. Oxidative damage and mitochondrial dysfunction are cofactors in the pathogenesis of diabetes, as well as major contributors to its associated complications, primarily represented by cardiovascular disease. In epilepsy, mitochondrial failure is thought to be one of the possible mechanisms for seizure generation through a dysregulation in calcium homeostasis; moreover, the prolonged seizure-related neuronal excitation is able to trigger mitochondrial damage, proving the existence of interdependency between epileptic activity and mitochondrial dysfunction. Oxidative stress plays a pivotal role in carcinogenesis, and its intervention has been demonstrated in the pathogenesis of cancer-prone genetic diseases. The identification of specific molecular targets linked to altered mitochondrial function allows to select more rational and appropriate supportive treatments using antioxidants and mitochondrial nutrients as potential new therapeutic approaches.

Conjunction of mitochondrial targeting nutrients for the management of heart dysfunctions associated with type 2 diabetes

Backgrounds and aims The heart is known to be susceptible to oxidative damage from high ambient oxidant levels, hypercoagulation and hypofibrinolysis associated with diabetes. It is also likely that poly(ADP-ribose)polymerase-1 (PARP-1) activation plays a crucial role in the pathogenesis of heart dysfunctions induced by diabetes. The study was performed to evaluate cardioprotective efficacy of a combined supplementation of mitochondria-specific antioxidants [acetyl-L-carnitine (ALC) and alpha-lipoic acid (ALA)] and nicotinamide (NAm), as a multiple-action drug in prevention of metabolic and haemostatic system's abnormalities induced by diabetes. Material and methods Neonatal diabetes was induced by STZ (80mg/kg b. w., i.p.) on the 2nd day of male Wistar rats' life. Rats were treated for 2 wks with or without combination of ALC, ALA and NAm (respectively 100, 50 and 100mg/kg b.w., i.p.) after 12 wks of STZ-induced diabetes. PARP-1 activity in heart was measured by the incorporation of radioactivity from NAD+ (labeled in the adenine moiety) into nuclei proteins. The metabolic and hemostatic system's parameters were also assessed. Results After 14 wks diabetic animals had not lost weight compared with control and treatment did not affect it, P P P P P Conclusion The findings suggest that combined supplement of naturally occurring biologically active compounds such as ALC, ALA and NAm offer a non-toxic, well tolerated and rational option for heart dysfunctions associated with type 2 diabetes improving metabolic and haemostatic system's alterations.

Dietary supplementation with coenzyme Q10 in poor responder patients undergoing IVF-ICSI Treatment

Ovarian aging and age-related reduction in live birth rate reflects a decline in response to ovarian stimulation, reduced embryo quality and pregnancy rate (PR), and an increased incidence of miscarriages and fetal aneuploidy. This is attributed to a high rate of aneuploidy and follicle depletion, probably due to energy-dependent mechanism as mitocondrial mutations in follicular cells increase with age and oxidative phosphorylation an ATP production in the follicle is also impaired in older women. Coenzyme Q10 (CoQ10) is a crucial substrate in the electron transport chain of mitochondria., and has been shown to decrease in several tissues with aging. The aim of this study was to asses if dietary supplementation of mitochondrial nutrients such as C0Q10 may improve mitochondrial energy production for the maturing oocyte and developing embryo, thereby improving ovarian response and reproductive outcome in poor responders. Prospective randomized controlled study. Seventy eight poor responders (36-40 years of age) in a previous IVF cycle according to Bologna criteria were randomized to Group 1 : 600 mg Co Q10 twice a day for 12 weeks and Group 2: no treatment for 12 weeks. Mean age was 37.8 yrs. in Group 1 and 37.2 yrs in group 2. Anti-Mullerian hormone (AMH) (0.67 +- 0.26vs 0.7 +-0.28) and FSH values (12 +- 2.11 vs 11.6 +- 1.89) were comparable. The primary outcomes were number of oocytes retrieved, number of good quality embryos obtained, pregnancy rate and live birth. Both groups were comparable in terms of age, BMI, ovarian reserve (AMH and FSH) and length of treatment. There were no significant differences in the number of MII oocytes retrieved (1.82 ± 0.82 vs. 1.87 ± 0.76; p=0.77), implantation rate (26.2% vs. 21.4%; p=0.75) and clinical pregnancy rate (fetal heartbeat at 7 weeks) (15.4% vs. 12.8%; p=0.64) No significant differences in outcome were detected between the CoQ10 and no treatment groups. However, the sample size of this study may be underpowered to detect a significant difference.

Coral calcium hydride prevents hepatic steatosis in high fat diet-induced obese rats: A potent mitochondrial nutrient and phase II enzyme inducer

Diet-induced nonalcoholic fatty liver disease (NAFLD) is characterized by profound lipid accumulation and associated with an inflammatory response, oxidative stress and hepatic mitochondrial dysfunction. We previously demonstrated that some mitochondrial nutrients effectively ameliorated high fat diet (HFD)-induced hepatic steatosis and metabolic disorders. Molecular hydrogen in hydrogen-rich liquid or inhaling gas, which has been confirmed in scavenging reactive oxygen species and preventing mitochondrial decay, improved metabolic syndrome in patients and animal models. Coral calcium hydride (CCH) is a new solid molecular hydrogen carrier made of coral calcium. However, whether and how CCH impacts HFD-induced hepatic steatosis remains uninvestigated. In the present study, we applied CCH to a HFD-induced NAFLD rat model for 13weeks. We found that CCH durably generated hydrogen in vivo and in vitro. CCH treatment significantly reduced body weight gain, improved glucose and lipid metabolism and attenuated hepatic steatosis in HFD-induced obese rats with no influence on food and water intake. Moreover, CCH effectively improved HFD-induced hepatic mitochondrial dysfunction, reduced oxidative stress, and activated phase II enzymes. Our results suggest that CCH is an efficient hydrogen-rich agent, which could prevent HFD-induced NAFLD via activating phase II enzymes and improving mitochondrial function.

Oocyte mitochondrial function and reproduction.

Mitochondria are cellular organelles that are required for energy production. Emerging evidence demonstrates their role in oocyte development and reproduction. In this review, we examine recent animal and clinical studies on the role of mitochondria in fertility. We also analyse the impact of assisted reproductive techniques (ARTs) on mitochondrial function and discuss the future clinical implications of mitochondrial nutrients and mitochondrial replacement. Mitochondria affect all aspects of mammalian reproduction. They are essential for optimal oocyte maturation, fertilization and embryonic development. Mitochondrial dysfunction causes a decrease in oocyte quality and interferes with embryonic development. ART procedures affect mitochondrial function, while mitochondrial nutrients may increase mitochondrial performance in oocytes. New mitochondrial replacement procedures using mitochondria obtained from polar bodies or from the patient's own oogonial stem cells are promising and may address concerns related to the induction of high-levels of heteroplasmy, which could potentially result in negative long-term health effects. Optimal energy production is required for oocyte and embryo development, and mitochondrial abnormalities have devastating reproductive consequences. Improvement of oocyte mitochondrial function via intake of compounds that boost mitochondrial activity may have clinical benefits, and mitochondrial replacement could potentially be used for the prevention of mitochondrial diseases.