scholarly journals Nuclear receptors and AMPK: can exercise mimetics cure diabetes?

2016 ◽  
Vol 57 (1) ◽  
pp. R49-R58 ◽  
Author(s):  
Christopher E Wall ◽  
Ruth T Yu ◽  
Anne R Atkins ◽  
Michael Downes ◽  
Ronald M Evans
Keyword(s):  
Metabolic Syndrome ◽  
Clinical Trials ◽  
Nuclear Receptors ◽  
Metabolic Diseases ◽  
Human Subjects ◽  
Molecular Targets ◽  
Disease Symptoms ◽  
Beneficial Effects ◽  
Increase Energy Expenditure ◽  
Exercise Mimetics

Endurance exercise can lead to systemic improvements in insulin sensitivity and metabolic homeostasis, and is an effective approach to combat metabolic diseases. Pharmacological compounds that recapitulate the beneficial effects of exercise, also known as ‘exercise mimetics’, have the potential to improve disease symptoms of metabolic syndrome. These drugs, which can increase energy expenditure, suppress hepatic gluconeogenesis, and induce insulin sensitization, have accordingly been highly scrutinized for their utility in treating metabolic diseases including diabetes. Nevertheless, the identity of an efficacious exercise mimetic still remains elusive. In this review, we highlight several nuclear receptors and cofactors that are putative molecular targets for exercise mimetics, and review recent studies that provide advancements in our mechanistic understanding of how exercise mimetics exert their beneficial effects. We also discuss evidence from clinical trials using these compounds in human subjects to evaluate their efficacy in treating diabetes.

scholarly journals Multifaceted Effect of Rubus Occidentalis on Hyperglycemia and Hypercholesterolemia in Mice with Diet-Induced Metabolic Diseases

Nutrients ◽  
2018 ◽  
Vol 10 (12) ◽  
pp. 1846 ◽  
Author(s):  
Jiyeon Kim ◽  
Jinho An ◽  
Heetae Lee ◽  
Kyungjae Kim ◽  
Su Lee ◽  
...  
Keyword(s):  
Metabolic Syndrome ◽  
Metabolic Diseases ◽  
Density Lipoprotein ◽  
Hdl Cholesterol ◽  
Experimental Period ◽  
Tolerance Test ◽  
Metabolic Phenotype ◽  
Simultaneous Occurrence ◽  
Beneficial Effects ◽  
Rubus Occidentalis

Metabolic syndrome is characterized by a combination of several metabolic disorders, including obesity, hyperglycemia, and hyperlipidemia. A simultaneous occurrence is one of the most crucial features of metabolic syndrome; therefore, we selected an animal model in which this would be reflected. We fed C57BL/6N mice a high-fat diet for 23 weeks to develop metabolic syndrome and examined the efficacy of Rubus occidentalis (RO) for hyperglycemia and hypercholesterolemia. Oral administration of RO for 16 weeks improved hyperglycemia as indicated by significantly decreased fasting glucose levels and a glucose tolerance test. Improvements were also observed in hypercholesterolemia, in which significant decreases in serum total cholesterol, non-high-density lipoprotein (non-HDL) cholesterol, apolipoprotein A-1, and apolipoprotein B levels were observed. The time comparison of major biomarkers, observed at the initiation and termination of the experimental period, consistently supported the beneficial effects of RO on each metabolic phenotype. In addition, RO treatment attenuated the excessive fat accumulation in hepatic and adipose tissue by decreasing the size and number of lipid droplets. These results suggested that RO simultaneously exerted antihyperglycemic and antihyperlipidemic effects in mice with diet-induced metabolic syndrome.

scholarly journals Developmental Programming of the Metabolic Syndrome: Can We Reprogram with Resveratrol?

2018 ◽  
Vol 19 (9) ◽  
pp. 2584 ◽  
Author(s):  
You-Lin Tain ◽  
Chien-Ning Hsu
Keyword(s):  
Metabolic Syndrome ◽  
Early Life ◽  
Wide Spectrum ◽  
Molecular Targets ◽  
Developmental Programming ◽  
Developmental Origins ◽  
Polyphenolic Compound ◽  
Beneficial Effects ◽  
The Metabolic Syndrome ◽  
Health And Disease

Metabolic syndrome (MetS) is a mounting epidemic worldwide. MetS can start in early life, in a microenvironment that is now known as the developmental origins of health and disease (DOHaD). The concept of DOHaD also offers opportunities for reprogramming strategies that aim to reverse programming processes in early life. Resveratrol, a polyphenolic compound has a wide spectrum of beneficial effects on human health. In this review, we first summarize the epidemiological and experimental evidence supporting the developmental programming of MetS. This review also presents an overview of the evidence linking different molecular targets of resveratrol to developmental programming of MetS-related disorders. This will be followed by studies documenting resveratrol as a reprogramming agent to protect against MetS-related disorders. Further clinical studies are required in order to bridge the gap between animal models and clinical trials in order to establish the effective dose and therapeutic duration for resveratrol as a reprogramming therapy on MetS disorders from developmental origins.

scholarly journals The role of bioactives in energy metabolism and metabolic syndrome

2019 ◽  
Vol 78 (3) ◽  
pp. 340-350 ◽  
Author(s):  
A. Bordoni ◽  
C. Boesch ◽  
C. Malpuech-Brugère ◽  
C. Orfila ◽  
L. Tomás-Cobos
Keyword(s):  
Metabolic Syndrome ◽  
Clinical Trials ◽  
Body Weight Gain ◽  
Alternative Therapy ◽  
Bioactive Molecules ◽  
Level Of Evidence ◽  
Beneficial Effects ◽  
Chain Pufa ◽  
Intervention Trials ◽  
Meta Analyses

Some food bioactives potentially exert anti-obesity effects. Anthocyanins (ACN), catechins, β-glucan (BG) and n-3 long chain PUFA (LCPUFA) are among the most promising candidates and have been considered as a strategy for the development of functional foods counteracting body weight gain. At present, clinical trials, reviews and meta-analyses addressing anti-obesity effects of various bioactives or bioactive-rich foods show contradictory results. Abdominal obesity is an important criterion for metabolic syndrome (MetS) diagnosis along with glucose intolerance, dyslipidaemia and hypertension. Food bioactives are supposed to exert beneficial effects on these parameters, therefore representing alternative therapy approaches for the treatment of MetS. This review summarises outcomes on MetS biomarkers in recent clinical trials supplementing ACN, catechins, BG and n-3 LCPUFA, focusing mainly on anti-obesity effects. Overall, it is clear that the level of evidence for the effectiveness varies not only among the different bioactives but also among the different putative health benefits suggested for the same bioactive. Limited evidence may be due to the low number of controlled intervention trials or to inconsistencies in trial design, i.e. duration, dose and/or the method of bioactive supplementation (extracts, supplements, rich or enriched food). At present, the question ‘Are bioactives effective in weight management and prevention of metabolic syndrome?’ remains inconclusive. Thus, a common effort to harmonise the study design of intervention trials focusing on the most promising bioactive molecules is urgently needed to strengthen the evidence of their potential in the treatment of obesity, MetS and related diseases.

scholarly journals Brown Seaweeds for the Management of Metabolic Syndrome and Associated Diseases

Molecules ◽  
2020 ◽  
Vol 25 (18) ◽  
pp. 4182
Author(s):  
Daniela Gabbia ◽  
Sara De Martin
Keyword(s):  
Metabolic Syndrome ◽  
Metabolic Diseases ◽  
Brown Seaweeds ◽  
Beneficial Effects ◽  
Associated Diseases ◽  
Preclinical And Clinical Studies

Metabolic syndrome is characterized by the coexistence of different metabolic disorders which increase the risk of developing type 2 diabetes mellitus and cardiovascular diseases. Therefore, metabolic syndrome leads to a reduction in patients’ quality of life as well as to an increase in morbidity and mortality. In the last few decades, it has been demonstrated that seaweeds exert multiple beneficial effects by virtue of their micro- and macronutrient content, which could help in the management of cardiovascular and metabolic diseases. This review aims to provide an updated overview on the potential of brown seaweeds for the prevention and management of metabolic syndrome and its associated diseases, based on the most recent evidence obtained from in vitro and in vivo preclinical and clinical studies. Owing to their great potential for health benefits, brown seaweeds are successfully used in some nutraceuticals and functional foods for treating metabolic syndrome comorbidities. However, some issues still need to be tackled and deepened to improve the knowledge of their ADME/Tox profile in humans, in particular by finding validated indexes of their absorption and obtaining reliable information on their efficacy and long-term safety.

scholarly journals Sources, isolation, characterisation and evaluation of probiotics

2013 ◽  
Vol 109 (S2) ◽  
pp. S35-S50 ◽  
Author(s):  
Luis Fontana ◽  
Miriam Bermudez-Brito ◽  
Julio Plaza-Diaz ◽  
Sergio Muñoz-Quezada ◽  
Angel Gil
Keyword(s):  
Gel Electrophoresis ◽  
Metabolic Diseases ◽  
Denaturing Gradient Gel Electrophoresis ◽  
Human Subjects ◽  
Functional Roles ◽  
Primer Selection ◽  
Beneficial Effects ◽  
Positive Effects ◽  
Clinical Benefits ◽  
Gradient Gel Electrophoresis

Probiotics are live microorganisms that, when ingested in adequate amounts, provide health benefits to the host. The strains most frequently used as probiotics include lactic acid bacteria and bifidobacteria, which are isolated from traditional fermented products and the gut, faeces and breast milk of human subjects. The identification of microorganisms is the first step in the selection of potential probiotics. The present techniques, including genetic fingerprinting, gene sequencing, oligonucleotide probes and specific primer selection, discriminate closely related bacteria with varying degrees of success. Additional molecular methods, such as denaturing gradient gel electrophoresis/temperature gradient gel electrophoresis and fluorescencein situhybridisation, are employed to identify and characterise probiotics. The ability to examine fully sequenced genomes has accelerated the application of genetic approaches to elucidate the functional roles of probiotics. One of the best-demonstrated clinical benefits of probiotics is the prevention and treatment of acute and antibiotic-associated diarrhoea; however, there is mounting evidence for a potential role for probiotics in the treatment of allergies and intestinal, liver and metabolic diseases. These positive effects are generally attributed to the ability of probiotics to regulate intestinal permeability, normalise host intestinal microbiota, improve gut immune barrier function and equilibrate the balance between pro-inflammatory and anti-inflammatory cytokines. However, the positive effects of probiotics are not always substantiated by findings from properly conducted clinical trials. Notably, even when the results from randomised, placebo-controlled trials support the beneficial effects of a particular probiotic for a specific indication, the benefits are generally not translatable to other probiotic formulations.

scholarly journals Are There Any Beneficial Effects of Spirulina Supplementation for Metabolic Syndrome Components in Postmenopausal Women?

Marine Drugs ◽  
2020 ◽  
Vol 18 (12) ◽  
pp. 651
Author(s):  
Elena Bobescu ◽  
Andreea Bălan ◽  
Marius Alexandru Moga ◽  
Andreea Teodorescu ◽  
Maria Mitrică ◽  
...  
Keyword(s):  
Metabolic Syndrome ◽  
Clinical Trials ◽  
Postmenopausal Women ◽  
Cardiovascular Events ◽  
Filamentous Cyanobacterium ◽  
Beneficial Effects ◽  
Positive Effects ◽  
The Metabolic Syndrome ◽  
Postmenopausal Period ◽  
Metabolic Syndrome Components

Spirulina is a phytosynthetic filamentous cyanobacterium with microscopic dimensions, which naturally grows in the highly-salted alkaline lakes of Africa, Mexico, America, and Asia. Several bioactive peptides extracted from Spirulina were demonstrated to possess antimicrobial, antiviral, antitumor, immunomodulatory, antiallergic and antihypertensive properties. It has been reported that the consumption of Spirulina could prevent or manage metabolic syndrome components. In women, metabolic disorders are more prevalent during menopause. Postmenopausal women present higher waist circumference, increased blood pressure, hypertriglyceridemia, hyperglycemia, and decreased HDL-cholesterol values, leading to an increased risk of cardiovascular events. Therefore, in order to prevent cardiovascular diseases, it is essential to manage the components of the metabolic syndrome during the postmenopausal period. As recent reports indicated the efficiency of Spirulina supplementation in the management of the metabolic syndrome components, our study aims to review all the clinical trials conducted on this topic. Our main objective is to have a better understanding of whether and how this cyanobacterium could manage the abnormalities included in the metabolic syndrome and if it could be used as a therapeutic approach in postmenopausal women with this condition. We selected relevant articles from PubMed, Google Scholar and CrossRef databases, and a total number of 20 studies met our criteria. All included clinical trials indicated that Spirulina has positive effects in managing metabolic syndrome components. Spirulina is a valuable cyanobacterium that can be used as a food supplement for the management of metabolic syndrome, and it is able to reduce the risk of cardiovascular events. The optimal dose and period of administration remain a debated subject, and future investigations are required. Considering the beneficial effects reported against each component of the metabolic syndrome, Spirulina could also be effective in the postmenopausal period, when this syndrome is the most prevalent, but there is a strong need for human clinical trials in order to sustain this observation.

scholarly journals Road to exercise mimetics: targeting nuclear receptors in skeletal muscle

2013 ◽  
Vol 51 (3) ◽  
pp. T87-T100 ◽  
Author(s):  
Weiwei Fan ◽  
Annette R Atkins ◽  
Ruth T Yu ◽  
Michael Downes ◽  
Ronald M Evans
Keyword(s):  
Skeletal Muscle ◽  
Physical Exercise ◽  
Nuclear Receptors ◽  
Beneficial Effects ◽  
The Metabolic Syndrome ◽  
Bona Fide ◽  
Exercise Mimetics ◽  
Exercise Induced ◽  
Muscle Energy Metabolism ◽  
Clinical Conditions

Skeletal muscle is the largest organ in the human body and is the major site for energy expenditure. It exhibits remarkable plasticity in response to physiological stimuli such as exercise. Physical exercise remodels skeletal muscle and enhances its capability to burn calories, which has been shown to be beneficial for many clinical conditions including the metabolic syndrome and cancer. Nuclear receptors (NRs) comprise a class of transcription factors found only in metazoans that regulate major biological processes such as reproduction, development, and metabolism. Recent studies have demonstrated crucial roles for NRs and their co-regulators in the regulation of skeletal muscle energy metabolism and exercise-induced muscle remodeling. While nothing can fully replace exercise, development of exercise mimetics that enhance or even substitute for the beneficial effects of physical exercise would be of great benefit. The unique property of NRs that allows modulation by endogenous or synthetic ligands makes them bona fide therapeutic targets. In this review, we present an overview of the current understanding of the role of NRs and their co-regulators in skeletal muscle oxidative metabolism and summarize recent progress in the development of exercise mimetics that target NRs and their co-regulators.

scholarly journals The Therapeutic Effects and Mechanisms of Quercetin on Metabolic Diseases: Pharmacological Data and Clinical Evidence

2021 ◽  
Vol 2021 ◽  
pp. 1-16
Author(s):  
Huan Yi ◽  
Hengyang Peng ◽  
Xinyue Wu ◽  
Xinmei Xu ◽  
Tingting Kuang ◽  
...  
Keyword(s):  
Metabolic Diseases ◽  
Human Subjects ◽  
Animal Experiments ◽  
Basic Research ◽  
Blood Lipid ◽  
Future Research ◽  
Therapeutic Effects ◽  
Nonalcoholic Fatty Liver ◽  
Hepatic Lipid Accumulation ◽  
Beneficial Effects

Metabolic diseases have become major public health issues worldwide. Searching for effective drugs for treating metabolic diseases from natural compounds has attracted increasing attention. Quercetin, an important natural flavonoid, is extensively present in fruits, vegetables, and medicinal plants. Due to its potentially beneficial effects on human health, quercetin has become the focus of medicinal attention. In this review, we provide a timely and comprehensive summary of the pharmacological advances and clinical data of quercetin in the treatment of three metabolic diseases, including diabetes, hyperlipidemia, and nonalcoholic fatty liver disease (NAFLD). Accumulating evidences obtained from animal experiments prove that quercetin has beneficial effects on these three diseases. It can promote insulin secretion, improve insulin resistance, lower blood lipid levels, inhibit inflammation and oxidative stress, alleviate hepatic lipid accumulation, and regulate gut microbiota disorders in animal models. However, human clinical studies on the effects of quercetin in diabetes, hyperlipidemia, and NAFLD remain scarce. More clinical trials with larger sample sizes and longer trial durations are needed to verify its true effectiveness in human subjects. Moreover, another important issue that needs to be resolved in future research is to improve the bioavailability of quercetin. This review may provide valuable information for the basic research, drug development, and clinical application of quercetin in the treatment of metabolic diseases.

scholarly journals Dietary Polyphenols in Metabolic Diseases and Neurodegeneration: Molecular Targets on Autophagy and Biological Effects

2020 ◽  
Author(s):  
Ana García-Aguilar ◽  
Olga Palomino Ruiz-Poveda ◽  
Manuel Benito de las Heras ◽  
Carlos Guillén Viejo
Keyword(s):  
Oxidative Stress ◽  
Cell Proliferation ◽  
Metabolic Diseases ◽  
Biological Effects ◽  
Molecular Targets ◽  
Biological Processes ◽  
Dietary Polyphenols ◽  
Beneficial Effects ◽  
Cardiovascular Damage ◽  
Obesity And Diabetes

Polyphenols represent a group of secondary metabolites of plants which have been analyzed as potent regulators of multiple biological processes, including cell proliferation, apoptosis and autophagy, among others. These natural compounds exhibit beneficial effects and protection against inflammation, oxidative stress and related injuries including metabolic diseases, such as cardiovascular damage, obesity and diabetes and neurodegeneration. In the present review, we report the main biological effects in relationship to autophagy regulation in response to different dietary polyphenols and its impact on metabolic and neurodegenerative diseases

Nuclear receptors in disease: the oestrogen receptors

2004 ◽  
Vol 40 ◽  
pp. 157-167 ◽  
Author(s):  
Maria Nilsson ◽  
Karin Dahlman-Wright ◽  
Jan-Åke Gustafsson
Keyword(s):  
Nuclear Receptors ◽  
Target Genes ◽  
Receptor Subtype ◽  
Target Tissue ◽  
Oestrogen Receptors ◽  
Nucleotide Polymorphisms ◽  
Cell Type ◽  
Single Nucleotide ◽  
Beneficial Effects ◽  
The Family

For several decades, it has been known that oestrogens are essential for human health. The discovery that there are two oestrogen receptors (ERs), ERalpha and ERbeta, has facilitated our understanding of how the hormone exerts its physiological effects. The ERs belong to the family of ligand-activated nuclear receptors, which act by modulating the expression of target genes. Studies of ER-knockout (ERKO) mice have been instrumental in defining the relevance of a given receptor subtype in a certain tissue. Phenotypes displayed by ERKO mice suggest diseases in which dysfunctional ERs might be involved in aetiology and pathology. Association between single-nucleotide polymorphisms (SNPs) in ER genes and disease have been demonstrated in several cases. Selective ER modulators (SERMs), which are selective with regard to their effects in a certain cell type, already exist. Since oestrogen has effects in many tissues, the goal with a SERM is to provide beneficial effects in one target tissue while avoiding side effects in others. Refined SERMs will, in the future, provide improved therapeutic strategies for existing and novel indications.

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