scholarly journals New Horizons: Circadian Control of Metabolism Offers Novel Insight Into the Cause and Treatment of Metabolic Diseases

2020 ◽  
Author(s):  
Shaunak Deota ◽  
Satchidananda Panda
Keyword(s):  
Circadian Rhythm ◽  
Metabolic Disorders ◽  
Metabolic Diseases ◽  
Caloric Intake ◽  
Regulatory System ◽  
New Drugs ◽  
New Horizons ◽  
Circadian Control ◽  
Sense And Respond ◽  
Preclinical Animal Models

Abstract Metabolic homeostasis is achieved by endocrine factors, signaling cascades, and metabolic pathways that sense and respond to metabolic demands in different organs. However, the recent discovery that almost every component of this regulatory system is also modulated by circadian rhythm highlights novel etiology and prognosis of metabolic diseases. First, chronic circadian rhythm disruption, as in shiftwork or shiftwork-like lifestyle, can increase the risk for metabolic diseases. Second, by understanding factors that affect circadian rhythm, we can implement new behavioral or pharmacological interventions for the prevention and management of metabolic disorders. One of these novel circadian-based interventions is time-restricted eating (TRE) in which all daily caloric intake is restricted to a consistent window of 8 to 12 hours. In preclinical animal models, TRE can prevent or reverse many metabolic diseases. Circadian research has also catalyzed attempts to optimally time the dosing of existing drugs to treat metabolic diseases or develop new drugs that target the circadian clock to treat metabolic disorders.

Pharmacological Targeting of Neuronal Kv7.2/3 Channels: A Focus on Chemotypes and Receptor Sites

2018 ◽  
Vol 25 (23) ◽  
pp. 2637-2660 ◽  
Author(s):  
Francesco Miceli ◽  
Maria V. Soldovieri ◽  
Paolo Ambrosino ◽  
Laura Manocchio ◽  
Ilaria Mosca ◽  
...  
Keyword(s):  
Metabolic Diseases ◽  
Scientific Literature ◽  
New Drugs ◽  
Current Status ◽  
Functional Heterogeneity ◽  
Molecular Scaffolds ◽  
Kv7 Channels ◽  
Receptor Sites ◽  
Pharmacological Targets ◽  
Pharmacological Potential

Background: The Kv7 (KCNQ) subfamily of voltage-gated potassium channels consists of 5 members (Kv7.1-5) each showing characteristic tissue distribution and physiological roles. Given their functional heterogeneity, Kv7 channels represent important pharmacological targets for the development of new drugs for neuronal, cardiovascular and metabolic diseases. <p> Objective: In the present manuscript, we focus on describing the pharmacological relevance and potential therapeutic applications of drugs acting on neuronally-expressed Kv7.2/3 channels, placing particular emphasis on the different chemotypes, and highlighting their pharmacodynamic and, whenever possible, pharmacokinetic peculiarities. <p> Methods: The present work is based on an in-depth search of the currently available scientific literature, and on our own experience and knowledge in the field of neuronal Kv7 channel pharmacology. Space limitations impeded to describe the full pharmacological potential of Kv7 channels; thus, we have chosen to focus on neuronal channels composed of Kv7.2 and Kv7.3 subunits, and to mainly concentrate on their involvement in epilepsy. <p> Results: An astonishing heterogeneity in the molecular scaffolds exploitable to develop Kv7.2/3 modulators is evident, with important structural/functional peculiarities of distinct compound classes. <p> Conclusion: In the present work we have attempted to show the current status and growing potential of the Kv7 pharmacology field. We anticipate a bright future for the field, and express our hopes that the efforts herein reviewed will result in an improved treatment of hyperexcitability (or any other) diseases.

The Effects of Coenzyme Q10 Supplementation on Lipid Profiles Among Patients with Metabolic Diseases: A Systematic Review and Meta-analysis of Randomized Controlled Trials

2018 ◽  
Vol 24 (23) ◽  
pp. 2729-2742 ◽  
Author(s):  
Nasrin Sharifi ◽  
Reza Tabrizi ◽  
Mahmood Moosazadeh ◽  
Naghmeh Mirhosseini ◽  
Kamran B. Lankarani ◽  
...  
Keyword(s):  
Systematic Review ◽  
Lipid Profile ◽  
Coenzyme Q10 ◽  
Metabolic Disorders ◽  
Metabolic Diseases ◽  
Meta Analysis ◽  
Lipid Profiles ◽  
Controlled Trials ◽  
Serum Triglycerides ◽  
Coq10 Supplementation

Background and objective: Oxidative stress and inflammation are key parameters in developing metabolic disorders. Hence, antioxidant intake might be an appropriate approach. Several studies have evaluated the effect of coenzyme Q10 (CoQ10) supplementation on lipid profile among patients with metabolic diseases, though findings are controversial. The aim of this systematic review and meta-analysis was to determine the effects of CoQ10 supplementation on lipid profile in patients with metabolic disorders. Methods: We searched PubMed, EMBASE, Web of Science and Cochrane Library databases until July 2017. Prospective clinical trials were selected assessing the effect of CoQ10 supplementation on different biomarkers. Two reviewers independently assessed the eligibility of studies, extracted data, and evaluated the risk of bias of included studies. A fixed- or random-effects model was used to pool the data, which expressed as a standardized mean difference with 95% confidence interval. Heterogeneity was measured using a Q-test and with I2 statistics. Results: A total of twenty-one controlled trials (514 patients and 525 controls) were included. The meta-analysis indicated a significant reduction in serum triglycerides levels (SMD -0.28; 95% CI, -0.56, -0.005). CoQ10 supplementation also decreased total-cholesterol (SMD -0.07; 95% CI, -0.45, 0.31), increased LDL- (SMD 0.04; 95% CI, -0.27, 0.36), and HDL-cholesterol levels (SMD 0.10; 95% CI, -0.32, 0.51), not statistically significant. Conclusion: CoQ10 supplementation may significantly reduce serum triglycerides levels, and help to improve lipid profiles in patients with metabolic disorders. Additional prospective studies are recommended using higher supplementation doses and longer intervention period.

INHERITED METABOLIC DISORDERS AND HEART DISEASES

2019 ◽  
Author(s):  
Vjekoslav Krželj ◽  
Ivana Čulo Čagalj
Keyword(s):  
Metabolic Disorders ◽  
Metabolic Diseases ◽  
Technological Development ◽  
Heart Diseases ◽  
Glycogen Storage ◽  
Acid Oxidation ◽  
Lysosomal Storage ◽  
Glycogen Storage Diseases ◽  
Coronary Diseases ◽  
Inherited Metabolic Disorders

Inherited metabolic disorders can cause heart diseases, cardiomyopathy in particular, as well as cardiac arrhythmias, valvular and coronary diseases. More than 40 different inherited metabolic disorders can provoke cardiomyopathy, including lysosomal storage disorders, fatty acid oxidation defects, organic acidemias, amino acidopathies, glycogen storage diseases, congenital disorders of glycosylation as well as peroxisomal and mitochondrial disorders. If identified and diagnosed on time, some of congenital metabolic diseases could be successfully treated. It is important to assume them in cases when heart diseases are etiologically undefined. Rapid technological development has made it easier to establish the diagnosis of these diseases. This article will focus on common inherited metabolic disorders that cause heart diseases, as well as on diseases that might be possible to treat.

scholarly journals Sex Differences in Rest-Activity Circadian Rhythm in Patients With Metabolic Syndrome

2021 ◽  
Vol 12 ◽  
Author(s):  
Antonino Mulè ◽  
Eleonora Bruno ◽  
Patrizia Pasanisi ◽  
Letizia Galasso ◽  
Lucia Castelli ◽  
...  
Keyword(s):  
Risk Factors ◽  
Metabolic Syndrome ◽  
Circadian Rhythm ◽  
Metabolic Diseases ◽  
Activity Level ◽  
Activity Count ◽  
Cross Sectional ◽  
The Metabolic Syndrome ◽  
Parametric Analyses ◽  
Rest Activity

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.

scholarly journals Ayurveda Internal Medicine for the Management of Common Metabolic Disorders W.S.R. to Madhumeha and Sthoulya

2019 ◽  
Vol 9 (5-s) ◽  
pp. 167-169
Author(s):  
Dhananjay S. Khot
Keyword(s):  
Internal Medicine ◽  
Metabolic Syndrome ◽  
Life Style ◽  
Metabolic Disorders ◽  
Dietary Habits ◽  
Metabolic Diseases ◽  
Health Issues ◽  
The Metabolic Syndrome ◽  
Sedentary Life Style

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.       

scholarly journals Empowering Melatonin Therapeutics with Drosophila Models

Diseases ◽  
2021 ◽  
Vol 9 (4) ◽  
pp. 67
Author(s):  
Cassandra Millet-Boureima ◽  
Caroline C. Ennis ◽  
Jurnee Jamison ◽  
Shana McSweeney ◽  
Anna Park ◽  
...  
Keyword(s):  
Circadian Rhythm ◽  
Model Organism ◽  
New Drugs ◽  
Renal Diseases ◽  
Disease Pathogenesis ◽  
Multiple Functions ◽  
Functional Conservation ◽  
Oxidative Response ◽  
Pharmacological Potential ◽  
Drosophila Models

Melatonin functions as a central regulator of cell and organismal function as well as a neurohormone involved in several processes, e.g., the regulation of the circadian rhythm, sleep, aging, oxidative response, and more. As such, it holds immense pharmacological potential. Receptor-mediated melatonin function mainly occurs through MT1 and MT2, conserved amongst mammals. Other melatonin-binding proteins exist. Non-receptor-mediated activities involve regulating the mitochondrial function and antioxidant cascade, which are frequently affected by normal aging as well as disease. Several pathologies display diseased or dysfunctional mitochondria, suggesting melatonin may be used therapeutically. Drosophila models have extensively been employed to study disease pathogenesis and discover new drugs. Here, we review the multiple functions of melatonin through the lens of functional conservation and model organism research to empower potential melatonin therapeutics to treat neurodegenerative and renal diseases.

scholarly journals Genome-Wide DNA Methylation Profiles of Phlegm-Dampness Constitution

2018 ◽  
Vol 45 (5) ◽  
pp. 1999-2008 ◽  
Author(s):  
Haiqiang Yao ◽  
Shanlan Mo ◽  
Ji Wang ◽  
Yingshuai Li ◽  
Chong-Zhi Wang ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Metabolic Disorders ◽  
Mononuclear Cells ◽  
Metabolic Diseases ◽  
Body Type ◽  
Peripheral Blood Mononuclear ◽  
Molecular Features ◽  
Genome Wide ◽  
A Genome ◽  
Differentially Methylated Genes

Background/Aims: Metabolic diseases are leading health concerns in today’s global society. In traditional Chinese medicine (TCM), one body type studied is the phlegm-dampness constitution (PC), which predisposes individuals to complex metabolic disorders. Genomic studies have revealed the potential metabolic disorders and the molecular features of PC. The role of epigenetics in the regulation of PC, however, is unknown. Methods: We analyzed a genome-wide DNA methylation in 12 volunteers using Illumina Infinium Human Methylation450 BeadChip on peripheral blood mononuclear cells (PBMCs). Eight volunteers had PC and 4 had balanced constitutions. Results: Methylation data indicated a genome-scale hyper-methylation pattern in PC. We located 288 differentially methylated probes (DMPs). A total of 256 genes were mapped, and some of these were metabolic-related. SQSTM1, DLGAP2 and DAB1 indicated diabetes mellitus; HOXC4 and SMPD3, obesity; and GRWD1 and ATP10A, insulin resistance. According to Ingenuity Pathway Analysis (IPA), differentially methylated genes were abundant in multiple metabolic pathways. Conclusion: Our results suggest the potential risk for metabolic disorders in individuals with PC. We also explain the clinical characteristics of PC with DNA methylation features.

Sign in / Sign up

Export Citation Format

Share Document