scholarly journals Melatonin Ameliorates Autophagy Impairment in a Metabolic Syndrome Model

Antioxidants ◽  
2021 ◽  
Vol 10 (5) ◽  
pp. 796
Author(s):  
Adrián Santos-Ledo ◽  
Beatriz de Luxán-Delgado ◽  
Beatriz Caballero ◽  
Yaiza Potes ◽  
Susana Rodríguez-González ◽  
...  

Metabolic syndrome is a global health problem in adults and its prevalence among children and adolescents is rising. It is strongly linked to a lifestyle with high-caloric food, which causes obesity and lipid metabolism anomalies. Molecular damage due to excessive oxidative stress plays a major role during the development of metabolic syndrome complications. Among the different hormones, melatonin presents strong antioxidant properties, and it is used to treat metabolic diseases. However, there is not a consensus about its use as a metabolic syndrome treatment. The aim of this study was to identify melatonin effects in a metabolic syndrome model. Golden hamsters were fed with 60% fructose-enriched food to induce metabolic syndrome and were compared to hamsters fed with regular chow diet. Both groups were also treated with melatonin. Fructose-fed hamsters showed altered blood lipid levels (increased cholesterol and LDL) and phenotypes restored with the melatonin treatment. The Harderian gland (HG), which is an ideal model to study autophagy modulation through oxidative stress, was the organ that was most affected by a fructose diet. Redox balance was altered in fructose-fed HG, inducing autophagic activation. However, since LC3-II was not increased, the impairment must be in the last steps of autophagy. Lipophagy HG markers were also disturbed, contributing to the dyslipidemia. Melatonin treatment improved possible oxidative homeostasis through autophagic induction. All these results point to melatonin as a possible treatment of the metabolic syndrome.

Endocrinology ◽  
2014 ◽  
Vol 155 (8) ◽  
pp. 2810-2819 ◽  
Author(s):  
Taichi Sugizaki ◽  
Mitsuhiro Watanabe ◽  
Yasushi Horai ◽  
Nao Kaneko-Iwasaki ◽  
Eri Arita ◽  
...  

Dyslipidemic patients with diabetes mellitus, including metabolic syndrome, are at increased risk of coronary heart disease. It has been reported that ezetimibe, a cholesterol absorption inhibitor, improves metabolic diseases in mice and humans. However, the underlying mechanism has been unclear. Here we explored the effects of ezetimibe on lipid and glucose homeostasis. Male KK-Ay mice were fed a high-fat diet, which is the mouse model of metabolic syndrome, with or without ezetimibe for 14 weeks. Ezetimibe improved dyslipidemia, steatosis, and insulin resistance. Ezetimibe decreased hepatic oxysterols, which are endogenous agonists of liver X receptor (LXR), to decrease hepatic lipogenic gene expressions, especially in stearoyl-CoA desaturase-1 (SCD1), leading to a remarkable reduction of hepatic oleate content that would contribute to the improvement of steatosis by reducing triglycerides and cholesterol esters. Simultaneously, hepatic β-oxidation, NADPH oxidase and cytochrome P450 2E1 (CYP2E1) were reduced, and thus reactive oxygen species (ROS) and inflammatory cytokines were also decreased. Consistent with these changes, ezetimibe diminished c-Jun N-terminal kinase (JNK) phosphorylation and improved insulin signaling in the liver. In vitro study using primary hepatocytes obtained from male SD rats, treated with oleate and LXR agonist, showed excess lipid accumulation, increased oxidative stress and impaired insulin signaling. Therefore, in obese subjects, ezetimibe reduces hepatic LXR activity by reducing hepatic oxysterols to lower hepatic oleate content. This improves steatosis and reduces oxidative stress, and this reduction improves insulin signaling in the liver. These results provide insight into pathogenesis and strategies for treatment of the metabolic syndrome.


2012 ◽  
Vol 2012 ◽  
pp. 1-13 ◽  
Author(s):  
Rebecca Hutcheson ◽  
Petra Rocic

The metabolic syndrome affects 30% of the US population with increasing prevalence. In this paper, we explore the relationship between the metabolic syndrome and the incidence and severity of cardiovascular disease in general and coronary artery disease (CAD) in particular. Furthermore, we look at the impact of metabolic syndrome on outcomes of coronary revascularization therapies including CABG, PTCA, and coronary collateral development. We also examine the association between the metabolic syndrome and its individual component pathologies and oxidative stress. Related, we explore the interaction between the main external sources of oxidative stress, cigarette smoke and air pollution, and metabolic syndrome and the effect of this interaction on CAD. We discuss the apparent lack of positive effect of antioxidants on cardiovascular outcomes in large clinical trials with emphasis on some of the limitations of these trials. Finally, we present evidence for successful use of antioxidant properties of pharmacological agents, including metformin, statins, angiotensin II type I receptor blockers (ARBs), and angiotensin II converting enzyme (ACE) inhibitors, for prevention and treatment of the cardiovascular complications of the metabolic syndrome.


2021 ◽  
Vol 6 (5) ◽  
pp. 408-413
Author(s):  
N. A. Markhon ◽  
◽  
V. М. Baibakov ◽  
V. A. Kosse ◽  
I. V. Lyulko ◽  
...  

The purpose of the study is to analyze the sources of modern literature of domestic and foreign researchers on the prospects of resveratrol in the prevention and treatment of metabolic syndrome. Metabolic syndrome is a clinical manifestation characterized by many comorbidities, including hyperglycemia, abdominal obesity, hypertension, and dyslipidemia. All components of metabolic syndrome are involved in the induction of low-quality inflammation and oxidative stress, characteristic of this symptom complex. Metabolic syndrome is associated with an increased risk of cardiovascular disease and early mortality, which has a significant impact on health care costs. Finding an effective and alternative therapeutic strategy, which is natural and has no side effects, can be a useful tool in the fight against metabolic syndrome. This review focuses on the potential beneficial effects of a polyphenolic natural compound – resveratrol – on various molecular targets with programming for the development of disorders associated with metabolic syndrome and its comorbidities. A number of data on the effects of resveratrol on body weight, insulin sensitivity, glucose tolerance, lipid profile, blood pressure, oxidative stress indicate that this compound has a wide range of beneficial effects on human health, and also has a beneficial effect on metabolic syndrome. A numerous data on the improvement of homeostasis, glucose, lipids, fat reduction, blood pressure, oxidative stress may demonstrate how resveratrol may be useful in the prevention and treatment of metabolic syndrome and related disorders due to its anti-inflammatory, antiplatelet and antioxidant properties. Resveratrol can be used either early as a reprogramming agent or later as a part of the treatment of metabolic syndrome. A few of the main molecular mechanisms underlying the beneficial effects of resveratrol on metabolic syndrome are given in the article. Conclusion. Presented review of literature outlined the potential of resveratrol as supplementary or alternative medicine. Thus, resveratrol could be a useful regimen for the prevention and treatment of metabolic syndrome and its related conditions. The article considers some molecular level targets for resveratrol in terms of its effect on the metabolic syndrome, such as adenosine monophosphate-activated protein kinase, SIRT1 protein, the main switch of the cellular defense system (Nrf2), nuclear factor-kappa B, estrogen receptor and the like


Planta Medica ◽  
2018 ◽  
Vol 84 (09/10) ◽  
pp. 568-583 ◽  
Author(s):  
Rabia Johnson ◽  
Dalene de Beer ◽  
Phiwayinkosi Dludla ◽  
Daneel Ferreira ◽  
Christo Muller ◽  
...  

AbstractAspalathin is a C-glucosyl dihydrochalcone that is abundantly present in Aspalathus linearis. This endemic South African plant, belonging to the Cape Floristic region, is normally used for production of rooibos, a herbal tea. Aspalathin was valued initially only as precursor in the formation of the characteristic red-brown colour of “fermented” rooibos, but the hype about the potential role of natural antioxidants to alleviate oxidative stress, shifted interest in aspalathin to its antioxidant properties and subsequently, its potential role to improve metabolic syndrome, a disease condition interrelated with oxidative stress. The potential use of aspalathin or aspalathin-rich rooibos extracts as a condition-specific nutraceutical is hampered by the limited supply of green rooibos (i.e., “unfermented” plant material) and low levels in “fermented” rooibos, providing incentive for its synthesis. In vitro and in vivo studies relating to the metabolic activity of aspalathin are discussed and cellular mechanisms by which aspalathin improves glucose and lipid metabolism are proposed. Other aspects covered in this review, which are relevant in view of the potential use of aspalathin as an adjunctive therapy, include its poor stability and bioavailability, as well as potential adverse herb-drug interactions, in particular interference with the metabolism of certain commonly prescribed chronic medications for hyperglycaemia and dyslipidaemia.


Biology ◽  
2021 ◽  
Vol 10 (4) ◽  
pp. 253
Author(s):  
Graciela Gavia-García ◽  
Juana Rosado-Pérez ◽  
Taide Laurita Arista-Ugalde ◽  
Itzen Aguiñiga-Sánchez ◽  
Edelmiro Santiago-Osorio ◽  
...  

A great amount of scientific evidence supports that Oxidative Stress (OxS) can contribute to telomeric attrition and also plays an important role in the development of certain age-related diseases, among them the metabolic syndrome (MetS), which is characterised by clinical and biochemical alterations such as obesity, dyslipidaemia, arterial hypertension, hyperglycaemia, and insulin resistance, all of which are considered as risk factors for type 2 diabetes mellitus (T2DM) and cardiovascular diseases, which are associated in turn with an increase of OxS. In this sense, we review scientific evidence that supports the association between OxS with telomere length (TL) dynamics and the relationship with MetS components in aging. It was analysed whether each MetS component affects the telomere length separately or if they all affect it together. Likewise, this review provides a summary of the structure and function of telomeres and telomerase, the mechanisms of telomeric DNA repair, how telomere length may influence the fate of cells or be linked to inflammation and the development of age-related diseases, and finally, how the lifestyles can affect telomere length.


2011 ◽  
Vol 7 (3) ◽  
pp. 219-227 ◽  
Author(s):  
Francesco Angelico ◽  
Lorenzo Loffredo ◽  
Pasquale Pignatelli ◽  
Teresa Augelletti ◽  
Roberto Carnevale ◽  
...  

Circulation ◽  
2008 ◽  
Vol 118 (suppl_18) ◽  
Author(s):  
Kaivan Khavandi ◽  
Adam Greenstein ◽  
Sarah Withers ◽  
Kazuhiko Sonoyama ◽  
Sarah Lewis ◽  
...  

In order to investigate the contribution of perivascular adipose tissue (PVAT) to arterial function, a total of 55 small arteries harvested from 35 skin biopsies of patients with Metabolic Syndrome and matched controls were mounted as ring preparations in a wire myograph. Contractility to cumulative doses of Norepinephrine in the presence or absence of PVAT showed an anticontractile effect in arteries from healthy volunteers (p=0.009), which was lost in patients with Metabolic Syndrome. Bioassay studies confirmed that PVAT releases a hydrophilic anticontractile factor in health, which is absent in obesity. Using a soluble fragment of the human Type 1 receptor, we identified that the anticontractile factor was adiponectin, which is the sole mediator of vasodilation, acting by increasing endothelial bioavailability of nitric oxide. Significant endothelial dysfunction was observed in patients with Metabolic Syndrome (p<0.001). Quantitative image analysis of adipose tissue revealed significantly increased adipocyte cell size in patients with Metabolic Syndrome, compared with healthy controls (p<0.006). There was immunohistochemical evidence of inflammation with upregulation of TNF-alpha receptor 1 in these patients (p<0.001). Application of exogenous TNF-alpha abolished the anticontractile effect of PVAT by reducing adiponectin bioavailability. Oxidative stress also induced by cytokines TNF-alpha and IL-6 but not IL-1, reduced adiponectin production from PVAT and increased basal tone. When the obese microenvironment was replicated in vitro by inflicting hypoxia on PVAT, adiponectin activity was lost but then rescued by incubation with cytokine antagonists. Further application of the adiponectin receptor fragment abolished PVAT relaxation. We conclude that in healthy arteries, PVAT releases adiponectin which reduces vascular tone. In obesity, this is lost by a cascade of adipocyte hypertrophy, hypoxia, inflammation and oxidative stress. The resulting vasoconstriction contributes to hypertension, hypertriglyceridaemia and insulin resistance. Direct targeting of adiponectin release from PVAT therefore provides a novel therapeutic opportunity in the Metabolic Syndrome.


2021 ◽  
Vol 12 ◽  
Author(s):  
Antonino Mulè ◽  
Eleonora Bruno ◽  
Patrizia Pasanisi ◽  
Letizia Galasso ◽  
Lucia Castelli ◽  
...  

Rest-Activity circadian Rhythm (RAR) can be used as a marker of the circadian timing system. Recent studies investigated the relationship between irregular circadian rhythms and cardiovascular risk factors such as hypertension, obesity, and dyslipidemia. These factors are related to the Metabolic Syndrome (MS), a clustering of metabolic risk factors that increases the risk of several cardiovascular and metabolic diseases. This cross-sectional analysis aimed to explore the RAR characteristics by actigraphy in subjects with MS, particularly in relation to sex and MS parameters, using parametric and non-parametric analyses. Distinguishing the characteristics of RAR based on sex could prove useful as a tool to improve the daily level of activity and set up customized activity programs based on each person’s circadian activity profile. This study showed that female participants exhibited higher values than male participants in the Midline Estimating Statistic of Rhythm (MESOR) (243.3 ± 20.0 vs 197.6 ± 17.9 activity count), Amplitude (184.5 ± 18.5 vs 144.2 ± 17.2 activity count), which measures half of the extent of the rhythmic variation in a cycle, and the most active 10-h period (M10) (379.08 ± 16.43 vs 295.13 ± 12.88 activity count). All these parameters are indicative of a higher daily activity level in women. Female participants also had lower Intradaily Variability (IV) than male participants (0.75 ± 0.03 vs 0.85 ± 0.03 activity count), which indicates a more stable and less fragmented RAR. These preliminary data provide the first experimental evidence of a difference in RAR parameters between male and female people with MS.


2019 ◽  
Vol 9 (5-s) ◽  
pp. 167-169
Author(s):  
Dhananjay S. Khot

The metabolic disorders are major health issues of today’s scenario and incidences of metabolic diseases increases day by day due to the disturbed pattern of life style. Ayurveda texts have described term “Santarpanjanya Vikaras” which resembles diseases of defective tissue metabolism. Ayurveda mentioned that improper dietary habits and sedentary life style affects state of Agni which resulted Ama production and finally leading to the metabolic syndrome. The vitiation of Dosha, diminish state of Dhatu and blockage of channels, etc. also can initiate pathogenesis of metabolic disorders. The Kayachikitsa branch of Ayurveda recommended use of internal medicine for the management of various metabolic disorders. Considering increased health burden of society due to the metabolic syndrome present article explore role of ayurveda internal medicine for the management of metabolic syndrome. Keywords: Ayurveda, metabolic syndrome, Santarpanjanya, Madhumeha and Sthoulya.       


Sign in / Sign up

Export Citation Format

Share Document