scholarly journals Neuroprotective Effects of Testosterone in the Hypothalamus of an Animal Model of Metabolic Syndrome

2021 ◽  
Vol 22 (4) ◽  
pp. 1589
Author(s):  
Erica Sarchielli ◽  
Paolo Comeglio ◽  
Sandra Filippi ◽  
Ilaria Cellai ◽  
Giulia Guarnieri ◽  
...  
Keyword(s):  
Metabolic Syndrome ◽  
Animal Model ◽  
Energy Homeostasis ◽  
Energy Status ◽  
Neuroprotective Effects ◽  
Beneficial Effects ◽  
Low Testosterone ◽  
Visceral Adipose ◽  
Immunohistochemical Analyses

Metabolic syndrome (MetS) is known to be associated to inflammation and alteration in the hypothalamus, a brain region implicated in the control of several physiological functions, including energy homeostasis and reproduction. Previous studies demonstrated the beneficial effects of testosterone treatment (TTh) in counteracting some MetS symptoms in both animal models and clinical studies. This study investigated the effect of TTh (30 mg/kg/week for 12 weeks) on the hypothalamus in a high-fat diet (HFD)-induced animal model of MetS, utilizing quantitative RT-PCR and immunohistochemical analyses. The animal model recapitulates the human MetS features, including low testosterone/gonadotropin plasma levels. TTh significantly improved MetS-induced hypertension, visceral adipose tissue accumulation, and glucose homeostasis derangements. Within hypothalamus, TTh significantly counteracted HFD-induced inflammation, as detected in terms of expression of inflammatory markers and microglial activation. Moreover, TTh remarkably reverted the HFD-associated alterations in the expression of important regulators of energy status and reproduction, such as the melanocortin and the GnRH-controlling network. Our results suggest that TTh may exert neuroprotective effects on the HFD-related hypothalamic alterations, with positive outcomes on the circuits implicated in the control of energy metabolism and reproductive tasks, thus supporting a possible role of TTh in the clinical management of MetS.

Dietary Carotenoids in Managing Metabolic Syndrome and Role of PPARs in the Process

2020 ◽  
Vol 16 (6) ◽  
pp. 846-853
Author(s):  
Raghunandan Purohith ◽  
Nagendra P.M. Nagalingaswamy ◽  
Nanjunda S. Shivananju
Keyword(s):  
Metabolic Syndrome ◽  
Dietary Intervention ◽  
Bioactive Constituents ◽  
Dietary Antioxidants ◽  
Predisposing Factor ◽  
Beneficial Effects ◽  
Pathological Conditions ◽  
Established Relationship ◽  
Comprehensive Study

Metabolic syndrome is a collective term that denotes disorder in metabolism, symptoms of which include hyperglycemia, hyperlipidemia, hypertension, and endothelial dysfunction. Diet is a major predisposing factor in the development of metabolic syndrome, and dietary intervention is necessary for both prevention and management. The bioactive constituents of food play a key role in this process. Micronutrients such as vitamins, carotenoids, amino acids, flavonoids, minerals, and aromatic pigment molecules found in fruits, vegetables, spices, and condiments are known to have beneficial effects in preventing and managing metabolic syndrome. There exists a well-established relationship between oxidative stress and major pathological conditions such as inflammation, metabolic syndrome, and cancer. Consequently, dietary antioxidants are implicated in the remediation of these complications. The mechanism of action and targets of dietary antioxidants as well as their effects on related pathways are being extensively studied and elucidated in recent times. This review attempts a comprehensive study of the role of dietary carotenoids in alleviating metabolic syndromewith an emphasis on molecular mechanism-in the light of recent advances.

Endokrinológiai tényezők és metabolikus folyamatok szerepe az élettartam szabályozásában

2021 ◽  
Vol 162 (33) ◽  
pp. 1318-1327
Author(s):  
Tamás Halmos ◽  
Ilona Suba
Keyword(s):  
Insulin Resistance ◽  
Metabolic Syndrome ◽  
Life Expectancy ◽  
Significant Risk ◽  
Low Grade ◽  
Aging Effects ◽  
Protective Function ◽  
Beneficial Effects ◽  
Age Related

Összefoglaló. Az emberek a lehető leghosszabb ideig akarnak élni, jó egészségben. Ha kiküszöbölnénk a kedvezőtlen külső körülményeket, a várható élettartam meghaladhatná a 100 évet. A 20. és 21. században a jóléti társadalmakban a várható élettartam jelentősen megnőtt, így Magyarországon is. Az áttekintett irodalom alapján megvizsgáltuk, hogy a genetika és az öröklődés mellett milyen endokrinológiai és metabolikus tényezők játszanak szerepet az élet meghosszabbításában. Megvizsgáltunk minden endogén tényezőt, amely pozitívan vagy negatívan befolyásolhatja az életkorral összefüggő betegségeket (Alzheimer-kór, szív- és érrendszeri betegségek, rák) és az élettartamot. Kiemeltük a hyperinsulinaemia, az inzulinrezisztencia, a metabolikus szindróma öregedést gyorsító hatását, az inzulinszerű növekedési hormon-1 ellentmondásos szerepét, valamint az élet meghosszabbításában részt vevő, újabban felfedezett peptideket, mint a klotho és a humanin. Ismertettük a mitochondriumok szerepét az élettartam meghatározásában, bemutattuk a mitohormesis folyamatát és annak stresszvédő funkcióját. Bemutattuk a rapamicin célszervét, az mTOR-t, amelynek gátlása meghosszabbítja az élettartamot, valamint a szirtuinokat. Kitértünk az autophagia folyamatára, és ismertettük a szenolitikumok szerepét az öregedésben. Az időskori autoimmunitás csökkenése hozzájárul az élettartam rövidüléséhez, utaltunk a thymus koordináló szerepére. Kiemeltük a bélmikrobiom fontos szerepét az élettartam szabályozásában. Hivatkoztunk a „centenáriusok” megfigyeléséből nyert humánadatokra. Megvizsgáltuk, milyen beavatkozási lehetőségek állnak rendelkezésre az egészségben tölthető élettartam meghosszabbításához. Az életmódbeli lehetőségek közül kiemeltük a kalóriabevitel-csökkentés és a testmozgás jótékony szerepét. Megvizsgáltuk egyes gyógyszerek feltételezett hatásait. Ezek közé tartozik a metformin, az akarbóz, a rezveratrol. E gyógyszerek mindegyikének hatása hasonló a kalóriamegszorításéhoz. Nincs olyan „csodaszer”, amely igazoltan meghosszabbítja az élettartamot emberben. Egyes géneknek és génmutációknak jótékony hatásuk van, de ezt környezeti tényezők, betegségek, balesetek és más külső ártalmak módosíthatják. Kiemeljük az elhízás, az alacsony fokozatú gyulladás és az inzulinrezisztencia öregedésre gyakorolt gyorsító hatását. A metabolikus szindróma elterjedtsége miatt ez jelentős népegészségügyi kockázatot jelent. Az inzulin, a növekedési hormon és az inzulinszerű növekedési faktorok hatásainak értékelése továbbra is ellentmondásos. Az egészséges, szellemileg és fizikailag aktív életmód, a kalóriacsökkentés mindenképpen előnyös. Az életet meghosszabbító szerek értékelése még vitatott. Orv Hetil. 2021; 162(33): 1318–1327. Summary. People want to live as long as possible in good health. If we eliminate the unfavorable external conditions, the life expectancy could exceed 100 years. In the 20th and 21th centuries, life expectancy in welfare societies increased significantly, including in Hungary. Based on the reviewed literature, we examined what endocrinological and metabolic factors play a role in prolonging life in addition to genetics and inheritance. We examined all endogenous factors that can positively or negatively affect age-related diseases (Alzheimer’s disease, cardiovascular disease, cancer) and longevity. We highlighted the aging effects of hyperinsulinemia, insulin resistance, metabolic syndrome, the controversial role of insulin-like growth factor-1, and more recently discovered peptides involved in prolonging lifespan, such as klotho and humanin. We described the role of mitochondria in determining longevity, we demonstrated the process of mitohormesis and its stress-protective function. We presented the target organ of rapamycin, mTOR, the inhibition of which prolongs lifespan, as well as sirtuins. We covered the process of autophagy and described the role of senolytics in aging. The decrease in autoimmunity in old age contributes to the shortening of life expectancy, we referred to the coordinating role of the thymus. We highlighted the important role of intestinal microbiome in the regulation of longevity. We referred to human data obtained from observations on “centenarians”. We examined what intervention options are available to prolong healthy life expectancy. Among the lifestyle options, we highlighted the beneficial role of calorie reduction and exercise. We examined the putative beneficial effects of some drugs. These include metformin, acarbose, resveratrol. The effect of each of these drugs is similar to calorie restriction. There is no “miracle cure” that has been shown to prolong life-span in humans. Some genes and gene mutations have beneficial effects, but this can be modified by environmental factors, diseases, accidents, and other external harms. We highlight the accelerating effects of obesity, low-grade inflammation, and insulin resistance on aging. Due to the prevalence of metabolic syndrome, this poses a significant risk to public health. The assessment of the effects of insulin, growth hormone, and insulin-like growth factors remains controversial. A healthy, mentally and physically active lifestyle, calorie reduction is definitely beneficial. The evaluation of life-prolonging agents is still controversial. Orv Hetil. 2021; 162(33): 1318–1327.

scholarly journals Neural Underpinnings of Obesity: The Role of Oxidative Stress and Inflammation in the Brain

Antioxidants ◽  
2020 ◽  
Vol 9 (10) ◽  
pp. 1018
Author(s):  
Caitlyn A. Mullins ◽  
Ritchel B. Gannaban ◽  
Md Shahjalal Khan ◽  
Harsh Shah ◽  
Md Abu B. Siddik ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Energy Homeostasis ◽  
Dorsal Striatum ◽  
Brain Regions ◽  
Therapeutic Interventions ◽  
Low Grade ◽  
Obesity Prevalence ◽  
Beneficial Effects ◽  
The Brain

Obesity prevalence is increasing at an unprecedented rate throughout the world, and is a strong risk factor for metabolic, cardiovascular, and neurological/neurodegenerative disorders. While low-grade systemic inflammation triggered primarily by adipose tissue dysfunction is closely linked to obesity, inflammation is also observed in the brain or the central nervous system (CNS). Considering that the hypothalamus, a classical homeostatic center, and other higher cortical areas (e.g. prefrontal cortex, dorsal striatum, hippocampus, etc.) also actively participate in regulating energy homeostasis by engaging in inhibitory control, reward calculation, and memory retrieval, understanding the role of CNS oxidative stress and inflammation in obesity and their underlying mechanisms would greatly help develop novel therapeutic interventions to correct obesity and related comorbidities. Here we review accumulating evidence for the association between ER stress and mitochondrial dysfunction, the main culprits responsible for oxidative stress and inflammation in various brain regions, and energy imbalance that leads to the development of obesity. Potential beneficial effects of natural antioxidant and anti-inflammatory compounds on CNS health and obesity are also discussed.

scholarly journals Functional Foods: An Approach to Modulate Molecular Mechanisms of Alzheimer’s Disease

Cells ◽  
2020 ◽  
Vol 9 (11) ◽  
pp. 2347
Author(s):  
Anna Atlante ◽  
Giuseppina Amadoro ◽  
Antonella Bobba ◽  
Valentina Latina
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Molecular Mechanisms ◽  
Food Product ◽  
Neuroprotective Effects ◽  
The Road ◽  
Beneficial Effects ◽  
Β Amyloid ◽  
The Brain

A new epoch is emerging with intense research on nutraceuticals, i.e., “food or food product that provides medical or health benefits including the prevention and treatment of diseases”, such as Alzheimer’s disease. Nutraceuticals act at different biochemical and metabolic levels and much evidence shows their neuroprotective effects; in particular, they are able to provide protection against mitochondrial damage, oxidative stress, toxicity of β-amyloid and Tau and cell death. They have been shown to influence the composition of the intestinal microbiota significantly contributing to the discovery that differential microorganisms composition is associated with the formation and aggregation of cerebral toxic proteins. Further, the routes of interaction between epigenetic mechanisms and the microbiota–gut–brain axis have been elucidated, thus establishing a modulatory role of diet-induced epigenetic changes of gut microbiota in shaping the brain. This review examines recent scientific literature addressing the beneficial effects of some natural products for which mechanistic evidence to prevent or slowdown AD are available. Even if the road is still long, the results are already exceptional.

Rhodiola and salidroside in the treatment of metabolic disorders

2019 ◽  
Vol 19 (19) ◽  
pp. 1611-1626 ◽  
Author(s):  
Xiang-Li Bai ◽  
Xiu-Ling Deng ◽  
Guang-Jie Wu ◽  
Wen-Jing Li ◽  
Si Jin
Keyword(s):  
Metabolic Disorders ◽  
Energy Homeostasis ◽  
Molecular Mechanisms ◽  
Metabolic Diseases ◽  
Ex Vivo ◽  
Treatment Strategies ◽  
Ampk Signaling ◽  
Beneficial Effects

Over the past three decades, the knowledge gained about the mechanisms that underpin the potential use of Rhodiola in stress- and ageing-associated disorders has increased, and provided a universal framework for studies that focused on the use of Rhodiola in preventing or curing metabolic diseases. Of particular interest is the emerging role of Rhodiola in the maintenance of energy homeostasis. Moreover, over the last two decades, great efforts have been undertaken to unravel the underlying mechanisms of action of Rhodiola in the treatment of metabolic disorders. Extracts of Rhodiola and salidroside, the most abundant active compound in Rhodiola, are suggested to provide a beneficial effect in mental, behavioral, and metabolic disorders. Both in vivo and ex vivo studies, Rhodiola extracts and salidroside ameliorate metabolic disorders when administered acutely or prior to experimental injury. The mechanism involved includes multi-target effects by modulating various synergistic pathways that control oxidative stress, inflammation, mitochondria, autophagy, and cell death, as well as AMPK signaling that is associated with possible beneficial effects on metabolic disorders. However, evidence-based data supporting the effectiveness of Rhodiola or salidroside in treating metabolic disorders is limited. Therefore, a comprehensive review of available trials showing putative treatment strategies of metabolic disorders that include both clinical effective perspectives and fundamental molecular mechanisms is warranted. This review highlights studies that focus on the potential role of Rhodiola extracts and salidroside in type 2 diabetes and atherosclerosis, the two most common metabolic diseases.

Curcumin dietary supplementation ameliorates disease phenotype in an animal model of Huntington’s disease.

2019 ◽  
Author(s):  
F Elifani ◽  
E Amico ◽  
G Pepe ◽  
L Capocci ◽  
S Castaldo ◽  
...  
Keyword(s):  
Animal Model ◽  
Huntington's Disease ◽  
Huntington’S Disease ◽  
Body Weight Loss ◽  
Beneficial Effects ◽  
Naturally Occurring ◽  
Human Pathology ◽  
The Brain

Abstract Huntington’s disease (HD) has traditionally been described as a disorder purely of the brain, however evidence indicates that peripheral abnormalities are also commonly seen. Among others, severe unintended body weight loss represents a prevalent and often debilitating feature of HD pathology, with no therapies available. It correlates with disease progression and significantly affects the quality of life of HD patients. Curcumin, a naturally occurring polyphenol with multiple therapeutic properties, has been validated to exert important beneficial effects under health conditions as well as in different pathological settings, including neurodegenerative and gastrointestinal (GI) disorders. Here, we investigated the potential therapeutic action that curcumin-supplemented diet may exert on central and peripheral dysfunctions in R6/2 mice, a well-characterized HD animal model which recapitulates some features of human pathology. Maintenance of normal motor function, protection from neuropathology and from GI dysfunction, preservation of GI emptying, and conserved intestinal contractility, proved the beneficial role of life-long dietary curcumin in HD and corroborated the potential of the compound to be exploited to alleviate very debilitating symptoms associated with the disease.

The role of AMP-activated protein kinase in the coordination of skeletal muscle turnover and energy homeostasis

2012 ◽  
Vol 303 (5) ◽  
pp. C475-C485 ◽  
Author(s):  
Anthony M. J. Sanchez ◽  
Robin B. Candau ◽  
Alfredo Csibi ◽  
Allan F. Pagano ◽  
Audrey Raibon ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Protein Kinase ◽  
Energy Homeostasis ◽  
Therapeutic Potential ◽  
Energy Status ◽  
Muscle Plasticity ◽  
Glucose And Lipid Metabolism ◽  
Muscle Homeostasis ◽  
Amp Activated Protein Kinase

The AMP-activated protein kinase (AMPK) is a serine/threonine protein kinase that acts as a sensor of cellular energy status switch regulating several systems including glucose and lipid metabolism. Recently, AMPK has been implicated in the control of skeletal muscle mass by decreasing mTORC1 activity and increasing protein degradation through regulation of ubiquitin-proteasome and autophagy pathways. In this review, we give an overview of the central role of AMPK in the control of skeletal muscle plasticity. We detail particularly its implication in the control of the hypertrophic and atrophic signaling pathways. In the light of these cumulative and attractive results, AMPK appears as a key player in regulating muscle homeostasis and the modulation of its activity may constitute a therapeutic potential in treating muscle wasting syndromes in humans.

scholarly journals Testosterone in COVID-19: An Adversary Bane or Comrade Boon

2021 ◽  
Vol 11 ◽  
Author(s):  
Hayder M. Al-kuraishy ◽  
Ali I. Al-Gareeb ◽  
Hani Faidah ◽  
Athanasios Alexiou ◽  
Gaber El-Saber Batiha
Keyword(s):  
Inflammatory Cytokines ◽  
Primary Source ◽  
Beneficial Effects ◽  
Pulmonary Manifestations ◽  
Low Testosterone ◽  
Low Levels ◽  
Testicular Injury ◽  
Respiratory Coronavirus ◽  
Harmful Effects

COVID-19 is a pandemic disease caused by severe acute respiratory coronavirus 2 (SARS-CoV-2), which leads to pulmonary manifestations like acute lung injury (ALI) and acute respiratory distress syndrome (ARDS). In addition, COVID-19 may cause extra-pulmonary manifestation such as testicular injury. Both high and low levels of testosterone could affect the severity of COVID-19. Herein, there is substantial controversy regarding the potential role of testosterone in SARS-CoV-2 infection and COVID-19 severity. Therefore, the present study aimed to review and elucidate the assorted view of preponderance regarding the beneficial and harmful effects of testosterone in COVID-19. A related literature search in PubMed, Scopus, Web of Science, Google Scholar, and Science Direct was done. All published articles related to the role of testosterone and COVID-19 were included in this mini-review. The beneficial effects of testosterone in COVID-19 are through inhibition of pro-inflammatory cytokines, augmentation of anti-inflammatory cytokines, modulation of the immune response, attenuation of oxidative stress, and endothelial dysfunction. However, its harmful effects in COVID-19 are due to augmentation of transmembrane protease serine 2 (TMPRSS2), which is essential for cleaving and activating SARS-CoV-2 spike protein during acute SARS-CoV-2 infection. Most published studies illustrated that low testosterone levels are linked to COVID-19 severity. A low testosterone level in COVID-19 is mainly due to testicular injury, the primary source of testosterone.

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