Mitochondria: It is all about energy

Frontiers in Physiology, Год журнала: 2023, Номер 14

Опубликована: Апрель 25, 2023

Mitochondria play a key role in both health and disease. Their function is not limited to energy production but serves multiple mechanisms varying from iron calcium homeostasis the of hormones neurotransmitters, such as melatonin. They enable influence communication at all physical levels through interaction with other organelles, nucleus, outside environment. The literature suggests crosstalk between mitochondria circadian clocks, gut microbiota, immune system. might even be hub supporting integrating activity across these domains. Hence, they (missing) link Mitochondrial dysfunction related metabolic syndrome, neuronal diseases, cancer, cardiovascular infectious inflammatory disorders. In this regard, diseases Alzheimer’s, Parkinson’s, amyotrophic lateral sclerosis (ALS), chronic fatigue syndrome (CFS), pain are discussed. This review focuses on understanding mitochondrial action that allow for maintenance pathways toward dysregulated mechanisms. Although have allowed us adapt changes over course evolution, turn, evolution has shaped mitochondria. Each evolution-based intervention influences its own way. use physiological stress triggers tolerance stressor, achieving adaptability resistance. describes strategies could recover functioning providing comprehensive, root-cause-focused, integrative approach recovering treating people suffering diseases.

Язык: Английский

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Oxidative Stress and Neurodegeneration in Animal Models of Seizures and Epilepsy

Antioxidants, Год журнала: 2023, Номер 12(5), С. 1049 - 1049

Опубликована: Май 5, 2023

Free radicals are generated in the brain, as well other organs, and their production is proportional to brain activity. Due its low antioxidant capacity, particularly sensitive free radical damage, which may affect lipids, nucleic acids, proteins. The available evidence clearly points a role for oxidative stress neuronal death pathophysiology of epileptogenesis epilepsy. present review devoted generation some animal models seizures epilepsy consequences stress, such DNA or mitochondrial damage leading neurodegeneration. Additionally, properties antiepileptic (antiseizure) drugs possible use compounds patients with reviewed. In numerous seizure models, concentration was significantly elevated. Some inhibit these effects; example, valproate reduced increase malondialdehyde (a marker lipid peroxidation) induced by electroconvulsions. pentylenetetrazol model, prevented glutathione an peroxidation products. scarce clinical data indicate that antioxidants (melatonin, selenium, vitamin E) be recommended adjuvants drug-resistant

Язык: Английский

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Body and mind: how obesity triggers neuropsychiatric and neurodegenerative disorders

Frontiers in Psychiatry, Год журнала: 2025, Номер 15

Опубликована: Янв. 7, 2025

Obesity has emerged as a significant health concern, particularly affecting young people worldwide.Its prevalence extends beyond Westernized countries and been projected to rise from 107.7 million obese children adolescents in 2015 254 by 2030 (1). This metabolic disorder poses severe consequences for healthcare systems globally, childhood obesity often persists into adulthood (2). Unlike other diseases, is pathological condition that renders individuals more susceptible various disorders, including syndrome, cardiovascular disease, nonalcoholic fatty liver cancer (3).Metabolic dysfunctions disrupt the structural functional of humans, central nervous system (CNS) (4). The hypothalamus, pivotal region situated between CNS periphery, serves control center energy homeostasis, body temperature, food intake, essential functions (5). Consuming diet high calories, carbohydrates lipids, triggers vicious cycle hyperactivation immune cells neuroinflammatory mediators within resulting widespread effects (6). Consequently, alterations this key brain led impairments all related neuronal circuits areas, mesolimbic dopamine (DA) system, hippocampus, nucleus accumbens, striatum, cortex, which are primarily associated with such cognition mood regulation.The gut microbiota plays role pathophysiology neuropsychiatric neurodegenerative context obesity. gut-brain axis mediates relationship (7). Obesity-induced peripheral influence function enhancing neuroinflammation, altering neurotransmitter synthesis, impairing insulin signaling These mechanisms have elevated risks depression, anxiety, cognitive decline, diseases (8). Specifically, Proteobacteria Cyanobacteria overrepresented patients (9,10). dysregulation metabolites these bacteria may contribute systemic inflammation oxidative damage, indirectly pathways relevant (11,12).Obesity disorders intricately interconnected, their share numerous characteristics (13). At level, obesity-related detrimental factors compromised integrity blood-brain barrier (BBB), prevents entry substances (14). BBB sophisticated highly specialized biological construct, characterized its selective permeability protective CNS. leads BBB, increased permeability, altered transport mechanisms, inflammatory responses Consistently, our findings indicate disruption induced high-fat (HFD) evidenced albumin extravasation hippocampus mice, represents critical mechanism pathogenesis (15). In condition, signals via gut-microbiotabrain can impact activity, both negatively positively metainflammation, levels pro-inflammatory mediators, activates astrogliosis microgliosis, leading neuroinflammation (16). microglia, resident CNS, (17). Under normal conditions, microglia maintain homeostasis regulating synaptic pruning clearing cellular debris. However, response chronic stress or inflammation, become activated release lead neurotoxicity (18). blocks machinery responsible neurogenesis, process renewal (19). Indeed, reduce neurogenesis suppressing stem cell proliferation, increasing apoptosis progenitor cells, decreasing survival newly developing neurons integration existing (20). Furthermore, long-term consumption Western-style HFD, low fiber content, substantial reduction short-chain acids, endogenous molecules notable anti-inflammatory neurogenesis-promoting properties (21). Our studies demonstrated HFD feeding depressive-and anxiety-like behavior intestinal dysbiosis, proliferation inflammatory-related microbes, alteration tryptophan metabolite pathway (22). production toxic tryptophan, quinolinic kynurenic acid, severally (23). neurobiological encompass reward circuitry, diminished serotonin (5-HT) DA levels, augmented hypothalamic-pituitary-adrenal (HPA) component body's (24). particular, known balance neurotransmitters regulation, 5-HT gammaaminobutyric acid (GABA). Elevated interleukin (IL)-6 tumor necrosis factor (TNF)-α serotonergic GABAergic systems, exacerbate symptoms (25). conditions serve etiological basis depressive anxiety phenotypes.Given growing intricate recent evidence also highlights shared mechanistic targets two conditions. For instance, peroxisome proliferator-activated receptor (PPAR)-α, whose lipid metabolism tissues well-established clinical therapy, recently recognized an tranquilizer caused dysmetabolism (26). PPAR-α widely distributed across amygdala, prefrontal thalamic nuclei, ventral tegmental area (VTA), basal ganglia (27). Moreover, research Jiang et al. (28) agonist WY14643 ameliorated depressive-like behaviors effect attributed activation Brain-Derived Neurotrophic Factor pathway.Neurodegenerative increasingly complex, bidirectional (29). Obesity, midlife, risk several Alzheimer's disease (AD), Parkinson's (PD), forms decline (30). correlation mediated combination metabolic, inflammatory, hormonal affect (31). resistance, changes (leptin adipokines), mitochondrial dysfunction, (32). Metainflammation, feature many dysmetabolism, impairs Neuroinflammation, turn, accelerates damage contributes progression. increases free radicals decreases antioxidant defenses, (33). process, coupled impaired function, damages structures, proteins, DNA, accelerating degeneration (34).Emerging underscores obesity, etiology AD, even if aging primary AD (35). Therefore, significantly correlates dysfunction (36). context, excessive weight processes derangements increase amyloid β (Aβ) accumulation (37). connection Aβ deposition; low-grade state, reactive oxygen species (38). (39). HFD-linked observed induce impair impacting (40).Notably, VTA, involved function.Different types HFDs alter potentially perceptions intake (41).Insulin influences transporter establishing outcomes (42). appears involve expression dopamine-degrading enzymes MAO-A MAO-B, reduces (43).Furthermore, microglial progression (44). interplay implies not only but through involving adipose tissue.While PD traditionally genetic environmental toxins, emerging indicates development (29).Specifically, suggested later life. mass index range at midlife exhibited higher likelihood years (45).Obesity linked worsening motor non-motor (46). It causing stiffness, flexibility, hindering physical already challenge PD. Additionally, older adults, be vascular health, worsen (47). during adipocytes cytokines TNF-α, IL-6, C-reactive protein (48).Lipid overnutrition subsequent metainflammation direct on brain, exacerbating player As it dopaminergic neurons, crucial (49). Since neurotoxic promote obesity-induced further activation, (50).At molecular regulate DA, contributing onset (51). Notably, leptin, produced adipocytes, regulation brain's (52). Research suggests leptin hallmark signal transduction, (53).The purpose opinion draw attention obesity-driven investigating how address "pandemic wellness." Identifying causal interrelationships comorbidities, although complex task, prevent counteract gluco-lipid dysmetabolism. scientific community made progress understanding pathogenic (Figure 1), there still much accomplish. contemplating possibly targeting due could innovative therapeutic strategies emphasizing necessity comprehensive approach takes account disorders.

Язык: Английский

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Long-term obesity impacts brain morphology, functional connectivity and cognition in adults

Nature Mental Health, Год журнала: 2025, Номер unknown

Опубликована: Март 3, 2025

Язык: Английский

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Dietary Polyphenols as a Protection against Cognitive Decline: Evidence from Animal Experiments; Mechanisms and Limitations

Antioxidants, Год журнала: 2023, Номер 12(5), С. 1054 - 1054

Опубликована: Май 5, 2023

Emerging evidence suggests that cognitive impairments may result from various factors, such as neuroinflammation, oxidative stress, mitochondrial damage, impaired neurogenesis, synaptic plasticity, blood–brain barrier (BBB) disruption, amyloid β protein (Aβ) deposition, and gut dysbiosis. Meanwhile, dietary polyphenol intake in a recommended dosage has been suggested to reverse dysfunction via pathways. However, excessive of polyphenols could trigger unwanted adverse effects. Thus, this review aims outline possible causes how alleviate memory loss pathways based on vivo experimental studies. identify potentially relevant articles, the keywords (1) nutritional intervention NOT medicine AND neuron growth OR (2) neurogenesis impairment (3) regeneration deterioration (Boolean operators) were used Nature, PubMed, Scopus, Wiley online libraries. Based inclusion exclusion criteria, 36 research papers selected be further reviewed. The outcome all studies included supports statement appropriate by taking into consideration gender differences, underlying conditions, lifestyle, causative factors for decline, which will significantly boost power. Therefore, recapitulates mechanism involving signaling modulating memory, dysbiosis, endogenous antioxidants, bioavailability, dosage, safety efficacy polyphenols. Hence, is expected provide basic understanding therapeutic development future.

Язык: Английский

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Diosmetin Ameliorates HFD-induced Cognitive Impairments via Inhibiting Metabolic Disorders, Mitochondrial Dysfunction and Neuroinflammation in Male SD Rats

Molecular Neurobiology, Год журнала: 2024, Номер 61(10), С. 8069 - 8085

Опубликована: Март 9, 2024

Язык: Английский

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Obesity-driven mitochondrial dysfunction in human adipose tissue-derived mesenchymal stem/stromal cells involves epigenetic changes

Cell Death and Disease, Год журнала: 2024, Номер 15(6)

Опубликована: Июнь 1, 2024

Abstract Obesity exacerbates tissue degeneration and compromises the integrity reparative potential of mesenchymal stem/stromal cells (MSCs), but underlying mechanisms have not been sufficiently elucidated. Mitochondria modulate viability, plasticity, proliferative capacity, differentiation MSCs. We hypothesized that alterations in 5-hydroxymethylcytosine (5hmC) profile mitochondria-related genes may mediate obesity-driven dysfunction human adipose-derived MSCs were harvested from abdominal subcutaneous fat obese age/sex-matched non-obese subjects ( n = 5 each). The 5hmC expression nuclear-encoded mitochondrial examined by hydroxymethylated DNA immunoprecipitation sequencing (h MeDIP-seq) mRNA-seq, respectively. MSC structure (electron microscopy) function, metabolomics, proliferation, neurogenic evaluated vitro, before after epigenetic modulation. hMeDIP-seq identified 99 peaks hyper-hydroxymethylation 150 hypo-hydroxymethylation Obese- versus Non-obese-MSCs. Integrated hMeDIP-seq/mRNA-seq analysis a select group overlapping (altered levels both mRNA) involved ATP production, redox activity, cell migration, fatty acid metabolism, neuronal development. Furthermore, Obese-MSCs exhibited decreased matrix density, membrane potential, metabolites, increased superoxide impaired differentiation, which improved with elicits changes MSCs, accompanied structural functional their mitochondria metabolism capacity. These observations assist developing novel therapies to preserve for repair regeneration individuals.

Язык: Английский

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Assessing the state of obesity care: Quality, access, guidelines, and standards

Obesity Science & Practice, Год журнала: 2024, Номер 10(4)

Опубликована: Июль 17, 2024

Abstract Background An international panel of obesity medicine experts from multiple professional organizations examined patterns care and current treatment guidelines to identify areas requiring updating in response emerging science clinical evidence. Aims The focused on medical health societal issues influencing effective identified several unmet needs the definition, assessment, obesity. Methods was held Leesburg, Virginia September 2019. Results panelists recommended addressing these through research, education, evaluation delivery payment care, practice (CPG) better reflect obesity’s pathophysiological basis heterogeneity, as well disease’s health, sociocultural, economic complications; effects quality life; need for standards quantitative comparison benefits, risks, costs; more effectively integrate into routine facilitate direct clinician participation improve public understanding a disease with basis. also that working people collaborate via group develop an updated, patient‐focused, comprehensive CPG establishing needs, providing routine, periodic review updating. Conclusions Unmet assessment were blueprint address developed guideline can be utilized worldwide respond increasing prevalence

Язык: Английский

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Altered hippocampal effective connectivity predicts BMI and food approach behavior in children with obesity

International Journal of Clinical and Health Psychology, Год журнала: 2025, Номер 25(1), С. 100541 - 100541

Опубликована: Янв. 1, 2025

The vicious circle model of obesity proposes that the hippocampus plays a crucial role in food reward processing and obesity. However, few studies focused on whether how pediatric influences potential direction information exchange between key regions, as well these alterations neural interaction could predict future BMI eating behaviors. In this longitudinal study, total 39 children with excess weight (overweight/obesity) 51 normal weight, aged 8 to 12, underwent resting-state fMRI. One year later, we conducted follow-up assessments behaviors BMI. Resting-state functional connectivity spectral dynamic casual modeling (spDCM) technique were used examine altered effective (EC) overweight/obesity. Linear support vector regression, machine learning method, was employed further investigate sensitive hippocampal connections at baseline Compared controls, displayed abnormal bidirectional inhibitory effects right left postcentral gyrus (PoCG), is, stronger hippocampus→PoCG EC but weaker PoCG→hippocampus EC, which predicted approach behavior one later. These findings point particularly important somatosensory cortex behavior, provide novel insights into hierarchical mechanisms underlying childhood expand spDCM adult by identifying directionality circuits associated appetitive regulation.

Язык: Английский

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Sarcopenic obesity and brain health: A critical appraisal of the current evidence

Nutrition Bulletin, Год журнала: 2025, Номер unknown

Опубликована: Янв. 12, 2025

Abstract Sarcopenic obesity (SO) is a body composition phenotype derived from the simultaneous presence in same individual of an increase fat mass and decrease skeletal muscle and/or function. Several protocols for diagnosis SO have been proposed last two decades making prevalence disease risk estimates heterogeneous challenging to interpret. Dementia complex neurological disorder that significantly impacts patients, carers healthcare systems. The identification factors early cognitive impairment dementia key mitigating forecasted trends 2‐fold case numbers over next worldwide. Excess adiposity sarcopenia both independently associated with dementia. Whether greater currently uncertain. This review critically appraises current evidence on association between outcomes risk. It also discusses some putative biological mechanisms may link alteration brain functions.

Язык: Английский

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