Body and mind: how obesity triggers neuropsychiatric and neurodegenerative disorders

Frontiers in Psychiatry, Journal Year: 2025, Volume and Issue: 15

Published: Jan. 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.

Language: Английский

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Lycopene: A Potent Antioxidant with Multiple Health Benefits

Journal of Nutrition and Metabolism, Journal Year: 2024, Volume and Issue: 2024(1)

Published: Jan. 1, 2024

Lycopene is a naturally occurring carotenoid predominantly found in tomatoes and tomato‐based products. Like other phytochemicals, it exhibits health beneficial biological activities that can be exploited when used as dietary supplement. In vitro vivo , lycopene has been demonstrated to mitigate oxidative stress‐induced metabolic dysfunctions diseases including inflammation, obesity, diabetes mellitus. shown alleviate affect the bone, eye, kidney, liver, lungs, heart, nervous system. This review presents state of art regarding lycopene’s benefits its potential applications system delivery. Furthermore, protective effects against toxins, safety use, possible toxicity are explored.

Language: Английский

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Mitigation of Insulin Resistance, Inflammation, Oxidative Stress, and Metabolic Abnormalities by Bavachalcone in High-Fat/High-Fructose Diet-Fed Rats

Indian Journal of Pharmaceutical Education and Research, Journal Year: 2025, Volume and Issue: 59(1), P. 134 - 143

Published: Jan. 6, 2025

Background Obesity is defined by an excess of body fat, together with insulin resistance and dyslipidemia. These factors significantly elevate the risk acquiring chronic disorders such as Diabetes Mellitus (DM), cardiovascular diseases, neurological disorders, etc. Objectives The goal current study was to evaluate bavachalcone's beneficial effects on obesity in experimental rats fed a High-Fat High-Fructose (HFa-HFr) diet. Materials Methods metabolic complications were induced HFa-HFr diet feeding for period 10 weeks treated bavachalcone from 5th 10th weeks. various parameters food water consumption, weight, insulin, blood glucose level, serum biochemical markers, liver oxidative stress proinflammatory cytokine levels assessed after treatment. Additionally, histopathological examination conducted tissues. Results findings showed that exhibited notable elevation glucose, fat deposits, marker enzyme activities. changes effectively mitigated Furthermore, resulted elevated accumulation, stress, inflammatory biomarker levels. In contrast, treatment successfully reduced resistance, deposition, inflammatory, conditions diet-fed rats. Conclusion results clearly diet-caused abnormalities reducing deposition markers. Keywords: Metabolic syndrome, Fatty liver, Bavachalcone, Insulin Inflammation

Language: Английский

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Exploring the Link between Oxidative Stress, Selenium Levels, and Obesity in Youth

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(13), P. 7276 - 7276

Published: July 2, 2024

Obesity is a worldwide increasing concern. Although in adults this easily estimated with the body mass index, children, who are constantly growing and whose bodies changing, reference points to assess weight status age gender, need corroboration complementary data, making their quantification highly difficult. The present review explores interaction spectrum of oxidative stress, selenium status, obesity children adolescents. Any factor related stress that triggers and, conversely, induces part vicious circle, complex chain mechanisms derive from each other reinforce serious health consequences. Selenium its compounds exhibit key antioxidant activity also have significant role nutritional evaluation obese children. balance intake, retention, metabolism emerges as vital aspect health, reflecting interactions between diet, obesity. Understanding whether contributor or consequence could inform interventions public strategies aimed at preventing managing an early age.

Language: Английский

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Cognitive Impairment and Synaptic Dysfunction in Cardiovascular Disorders: The New Frontiers of the Heart–Brain Axis

Biomedicines, Journal Year: 2024, Volume and Issue: 12(10), P. 2387 - 2387

Published: Oct. 18, 2024

Within the central nervous system, synaptic plasticity, fundamental to processes like learning and memory, is largely driven by activity-dependent changes in strength. This plasticity often manifests as long-term potentiation (LTP) depression (LTD), which are bidirectional modulations of efficacy. Strong epidemiological experimental evidence show that heart-brain axis could be severely compromised both neurological cardiovascular disorders. Particularly, disorders, such heart failure, hypertension, obesity, diabetes insulin resistance, arrhythmias, may lead cognitive impairment, a condition known cardiogenic dementia. Herein, we review available knowledge on molecular mechanisms dementia arise describe how LTP and/or LTD induction maintenance CA1 region hippocampus metabolic syndrome, arrhythmias. We also discuss emerging endothelial dysfunction contribute directly altering hippocampal impairing synaptically induced activation nitric oxide synthase. A better understanding CV disorders impact proper function synapses will shed novel light underpinnings dementia, thereby providing new perspective for more specific pharmacological treatments.

Language: Английский

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Functional effects and mechanisms of Phyllanthus emblica fruit and gallic acid on metabolic diseases: Experimental evidence and clinical perspectives

Food Bioscience, Journal Year: 2024, Volume and Issue: 59, P. 104039 - 104039

Published: April 7, 2024

Language: Английский

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Oxidative stress and type 2 diabetes: the development and the pathogenesis, Jordanian cross-sectional study

European journal of medical research, Journal Year: 2024, Volume and Issue: 29(1)

Published: July 17, 2024

Abstract Accumulation of reactive oxygen species (ROS) can disrupt the antioxidant defense system, leading to oxidative stress that leads pathological damage vital human organs, including hormone-producing glands. Normal physiological function is subsequently disrupted and disorders such as Type 2 Diabetes Mellitus (T2DM) may develop. The critical role system in counteracting ROS mitigating fundamental understanding pathogenesis T2DM. In our study, we monitored oxidant/antioxidant status a selected Jordanian population further elucidate this relationship. Our results show higher serum levels Malondialdehyde (MDA); 0.230 ± 0.05 0.207 0.06 μmol/l for diabetic obese groups, respectively, relative 0.135 0.04 non-obese healthy group. Lower activity Catalase (CAT) was recorded among (9.2 3.2) groups (11.0 2.8), compared group (12.1 3.5). Significant elevations ( P < 0.05) were observed uric acid concentrations subjects: 451 57 mg/dl 430 51, versus 342 Moreover, no significant differences obtained between all studied albumin total protein concentrations. findings demonstrate potential development occurrence

Language: Английский

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The association between Weight-adjusted-Waist Index (WWI) and cognitive function in older adults: a cross-sectional NHANES 2011–2014 study

BMC Public Health, Journal Year: 2024, Volume and Issue: 24(1)

Published: Aug. 8, 2024

The impact of obesity on cognitive function has engendered considerable interest. Weight-adjusted waist index (WWI) emerged as a novel and innovative marker that reflects weight-independent abdominal obesity. However, the association between WWI remains unclear. To address this gap, present study aims to explore relationship weight-adjusted performance in older adults.

Language: Английский

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Elucidating the effect of camel α-lactalbumin in modulating obesity-related metabolic disorders in an obese rat model

International Journal of Biological Macromolecules, Journal Year: 2025, Volume and Issue: 295, P. 139693 - 139693

Published: Jan. 8, 2025

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Exploring the application of dietary antioxidant index for disease risk assessment: a comprehensive review

Frontiers in Nutrition, Journal Year: 2025, Volume and Issue: 11

Published: Jan. 16, 2025

Oxidative stress contributes to the development of cardiometabolic diseases and cancers. Numerous studies have highlighted adverse effects high reactive oxygen species (ROS) levels in progression chronic noncommunicable also during infections. On other hand, antioxidants play a crucial role preventing oxidative or postponing cell damage via direct scavenging free radicals indirectly Keap1/Nrf2/ARE pathway, among others. Dietary can be obtained from various sources, mainly through plant-based diet, including fruits vegetables. The dietary antioxidant index (DAI) has been developed assess total intake diet. This review delineated performance DAI risk assessment different diseases. It is suggested that score prevents obesity-related diseases, diabetes mellitus, hyperuricemia, dyslipidemia, metabolic (dysfunction)-associated steatotic liver disease (MASLD). Additionally, negatively associated with Helicobacter pylori Human papillomavirus infection, thus reducing gastric cervical cancer. Also, osteoporosis, miscarriage, infertility, mental illnesses. However, further prospective observations clinical trials are warranted confirm application studied.

Language: Английский

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