scholarly journals Curcumin and other dietary polyphenols: potential mechanisms of metabolic actions and therapy for diabetes and obesity

2018 ◽  
Vol 314 (3) ◽  
pp. E201-E205 ◽  
Author(s):  
Tianru Jin ◽  
Zhuolun Song ◽  
Jianping Weng ◽  
I. George Fantus
Keyword(s):  
Metabolic Regulation ◽  
Metabolic Diseases ◽  
Therapeutic Potential ◽  
Body Weight Gain ◽  
Metabolic Effects ◽  
Dietary Polyphenols ◽  
Obesity And Diabetes ◽  
Clinical Investigations ◽  
Diabetes Development ◽  
Diabetes And Obesity

Recent controversy regarding the therapeutic potential of curcumin indicates the challenges to research in this field. Here, we highlight the investigations of curcumin and other plant-derived polyphenols that demonstrate their application to metabolic diseases, in particular, obesity and diabetes. Thus, a number of preclinical and clinical investigations have shown the beneficial effect of curcumin (and other dietary polyphenols) in attenuating body weight gain, improving insulin sensitivity, and preventing diabetes development in rodent models and prediabetic subjects. Other intervention studies with dietary polyphenols have also found improvements in insulin resistance. Recent studies suggest that the metabolic effects of curcumin/polyphenols are linked to changes in the gut microbiota. Thus, research into curcumin continues to provide novel insights into metabolic regulation that may ultimately translate into effective therapy.

scholarly journals Long-term effects of ghrelin and ghrelin receptor agonists on energy balance in rats

2008 ◽  
Vol 295 (1) ◽  
pp. E78-E84 ◽  
Author(s):  
Sabine Strassburg ◽  
Stefan D. Anker ◽  
Tamara R. Castaneda ◽  
Lukas Burget ◽  
Diego Perez-Tilve ◽  
...  
Keyword(s):  
Body Weight ◽  
Energy Balance ◽  
Food Intake ◽  
Energy Expenditure ◽  
Therapeutic Potential ◽  
Body Weight Gain ◽  
Metabolic Effects ◽  
Positive Energy ◽  
High Dose ◽  
Growth Hormone Secretagogue

Ghrelin, an endogenous ligand of the growth hormone secretagogue receptor (GHS-R), is the only circulating agent to powerfully promote a positive energy balance. Such action is mediated predominantly by central nervous system pathways controlling food intake, energy expenditure, and nutrient partitioning. The ghrelin pathway may therefore offer therapeutic potential for the treatment of catabolic states. However, the potency of the endogenous hormone ghrelin is limited due to a short half-life and the fragility of its bioactivity ensuring acylation at serine 3. Therefore, we tested the metabolic effects of two recently generated GHS-R agonists, BIM-28125 and BIM-28131, compared with ghrelin. All agents were administered continuously for 1 mo in doses of 50 and 500 nmol·kg−1·day−1 using implanted subcutaneous minipumps in rats. High-dose treatment with single agonists or ghrelin increased body weight gain by promoting fat mass, whereas BIM-28131 was the only one also increasing lean mass significantly. Food intake increased during treatment with BIM-28131 or ghrelin, whereas no effects on energy expenditure were detected. With the lower dose, only BIM-28131 had a significant effect on body weight. This also held true when the compound was administered by subcutaneous injection three times/day. No symptoms or signs of undesired effects were observed in any of the studies or treated groups. These results characterize BIM-28131 as a promising GHS-R agonist with an attractive action profile for the treatment of catabolic disease states such as cachexia.

scholarly journals The Role of Bioactive Peptides in Diabetes and Obesity

Foods ◽  
2021 ◽  
Vol 10 (9) ◽  
pp. 2220
Author(s):  
Ramachandran Chelliah ◽  
Shuai Wei ◽  
Eric Banan-Mwine Daliri ◽  
Fazle Elahi ◽  
Su-Jung Yeon ◽  
...  
Keyword(s):  
Drug Targets ◽  
Bioactive Peptides ◽  
Metabolic Diseases ◽  
Food Protein ◽  
Protein Fragments ◽  
Obesity And Diabetes ◽  
New Ideas ◽  
Diabetes And Obesity ◽  
Metabolic Syndromes

Bioactive peptides are present in most soy products and eggs and have essential protective functions. Infection is a core feature of innate immunity that affects blood pressure and the glucose level, and ageing can be delayed by killing senescent cells. Food also encrypts bioactive peptides and protein sequences produced through proteolysis or food processing. Unique food protein fragments can improve human health and avoid metabolic diseases, inflammation, hypertension, obesity, and diabetes mellitus. This review focuses on drug targets and fundamental mechanisms of bioactive peptides on metabolic syndromes, namely obesity and type 2 diabetes, to provide new ideas and knowledge on the ability of bioactive peptide to control metabolic syndromes.

scholarly journals Scaffold Proteins: From Coordinating Signaling Pathways to Metabolic Regulation

Endocrinology ◽  
2018 ◽  
Vol 159 (11) ◽  
pp. 3615-3630 ◽  
Author(s):  
Yves Mugabo ◽  
Gareth E Lim
Keyword(s):  
Signaling Pathways ◽  
Chronic Conditions ◽  
Metabolic Regulation ◽  
Metabolic Diseases ◽  
Scaffold Proteins ◽  
Present Review ◽  
Therapeutic Approaches ◽  
The Past ◽  
Pleiotropic Functions ◽  
Diabetes And Obesity

Abstract Among their pleiotropic functions, scaffold proteins are required for the accurate coordination of signaling pathways. It has only been within the past 10 years that their roles in glucose homeostasis and metabolism have emerged. It is well appreciated that changes in the expression or function of signaling effectors, such as receptors or kinases, can influence the development of chronic diseases such as diabetes and obesity. However, little is known regarding whether scaffolds have similar roles in the pathogenesis of metabolic diseases. In general, scaffolds are often underappreciated in the context of metabolism or metabolic diseases. In the present review, we discuss various scaffold proteins and their involvement in signaling pathways related to metabolism and metabolic diseases. The aims of the present review were to highlight the importance of scaffold proteins and to raise awareness of their physiological contributions. A thorough understanding of how scaffolds influence metabolism could aid in the discovery of novel therapeutic approaches to treat chronic conditions, such as diabetes, obesity, and cardiovascular disease, for which the incidence of all continue to increase at alarming rates.

scholarly journals Effect of Lippia alba essential oil administration on obesity and T2DM markers in Wistar rats

2019 ◽  
Vol 48 (2) ◽  
pp. 411-424
Author(s):  
Maria Victoria Acevedo-Estupiñan ◽  
Elena Stashenko ◽  
Fernando Rodríguez-Sanabria
Keyword(s):  
Essential Oil ◽  
Wistar Rats ◽  
Body Weight Gain ◽  
Metabolic Effects ◽  
Human Beings ◽  
Lippia Alba ◽  
Obesity And Diabetes ◽  
Lower Glucose ◽  
Elisa Technique ◽  
America South

Introduction: Lippia alba (Mill) N.E. Brown (Verbenaceae) is an aromatic plant from Central America, South America, and the Caribbean, it is traditionally used by the Colombian population to treat various diseases such as diabetes and hypertension. The purpose of this research was to evaluate the metabolic effects of Lippia alba essential oil (EO) oral administration on obesity and diabetes markers in Wistar rats. Methods: control and Streptozotocin (STZ) diabetes induced rats were used to evaluate the EO metabolic effects. Glucose and triglycerides were measured using commercial colorimetric kits, the animals’ weight was followed for 21 days treatment and TNF- and adiponectin concentration was determined with ELISA technique. Results: The consumption of EO shows body weight gain regulation, lower glucose and cholesterol levels in normal rats and lower TNF- in comparison with the Glibenclamide treated rats between the STZ diabetic groups. No toxic effects were founded. Conclusions: The EO exerts a benefical metabolic effect in rats, therefore it is interesting to be evaluate a future in human beings with T2DM or overweight.

Fed-EXosome: extracellular vesicles and cell–cell communication in metabolic regulation

2018 ◽  
Vol 62 (2) ◽  
pp. 165-175 ◽  
Author(s):  
Isabella Samuelson ◽  
Antonio J. Vidal-Puig
Keyword(s):  
Extracellular Vesicles ◽  
Cross Talk ◽  
Metabolic Regulation ◽  
Metabolic Diseases ◽  
Whole Body ◽  
Target Cells ◽  
Metabolic Complications ◽  
Obesity And Diabetes ◽  
Lipid Species ◽  
Cell Cell

Extracellular vesicles (EVs) have emerged as a novel messaging system of the organism, mediating cell–cell and interorgan communication. Through their content of proteins and nucleic acids, as well as membrane proteins and lipid species, EVs can interact with and modulate the function of their target cells. The regulation of whole-body metabolism requires cross-talk between key metabolic tissues including adipose tissue (AT), the liver and skeletal muscle. Furthermore, the regulation of nutrient/energy allocation during pregnancy requires co-ordinated communication between the foetus and metabolic organs of the mother. A growing body of evidence is suggesting that EVs play a role in communication between and within key metabolic organs, both physiologically during metabolic homoeostasis but also contributing to pathophysiology during metabolic dysregulation observed in metabolic diseases such as obesity and diabetes. As obesity and its associated metabolic complications are reaching epidemic proportions, characterization of EV-mediated communication between key metabolic tissues may offer important insights into the regulation of metabolic functions during disease and offer global therapeutic opportunities. Here, we focus on the role of EVs in metabolic regulation and, in particular, EV-mediated cross-talk between cells of the AT.

scholarly journals Erythropoietin treatment leads to reduced blood glucose levels and body mass: insights from murine models

2010 ◽  
Vol 205 (1) ◽  
pp. 87-95 ◽  
Author(s):  
Odelia Katz ◽  
Matthew Stuible ◽  
Nathalia Golishevski ◽  
Lilach Lifshitz ◽  
Michel L Tremblay ◽  
...  
Keyword(s):  
Body Weight ◽  
Blood Glucose ◽  
Therapeutic Potential ◽  
Body Weight Gain ◽  
Murine Models ◽  
Erythroid Precursor ◽  
Glucose Levels ◽  
Blood Glucose Levels ◽  
Wide Range ◽  
Diabetes And Obesity

Erythropoietin (EPO) regulates proliferation and differentiation of erythroid precursor cells into erythrocytes. The last decade has revealed non-renal sites of EPO production and extrahematopoietic expression of the EPO receptor, thus suggesting that EPO has pleiotropic functions. Here, we addressed the interplay between EPO/glucose metabolism/body weight by employing a panel of relevant experimental murine models. The models focused on situations of increased EPO levels, including EPO-injected C57BL/6 and BALB/c mice, as well as transgenic mice (tg6) constitutively overexpressing human EPO, thus exposed to constantly high EPO serum levels. As experimental models for diabetes and obesity, we employed protein Tyr phosphatase 1B (PTP1B) knockout mice associated with resistance to diabetes (PTP1B−/−), and ob/ob mice susceptible to diabetes and obesity. The data presented herein demonstrate EPO-mediated decrease in blood glucose levels in all mice models tested. Moreover, in the ob/ob mice, we observed EPO-mediated attenuation of body weight gain and reduction of hemoglobin A1c. Taken together, our data bear significant clinical implications of EPO treatment in the management of a wide range of metabolic diseases, thus adding an important novel therapeutic potential to this pleiotropic hormone.

scholarly journals Hydrogen Therapy in Cardiovascular and Metabolic Diseases: from Bench to Bedside

2018 ◽  
Vol 47 (1) ◽  
pp. 1-10 ◽  
Author(s):  
Yaxing Zhang ◽  
Sihua Tan ◽  
Jingting Xu ◽  
Tinghuai Wang
Keyword(s):  
Molecular Mechanisms ◽  
Ventricular Remodeling ◽  
Metabolic Diseases ◽  
Therapeutic Potential ◽  
Chemical Properties ◽  
Obesity And Diabetes ◽  
Gas Molecules ◽  
Heart Injury ◽  
Physical And Chemical ◽  
And Chemical Properties

Hydrogen (H2) is colorless, odorless, and the lightest of gas molecules. Studies in the past ten years have indicated that H2 is extremely important in regulating the homeostasis of the cardiovascular system and metabolic activity. Delivery of H2 by various strategies improves cardiometabolic diseases, including atherosclerosis, vascular injury, ischemic or hypertrophic ventricular remodeling, intermittent hypoxia- or heart transplantation-induced heart injury, obesity and diabetes in animal models or in clinical trials. The purpose of this review is to summarize the physical and chemical properties of H2, and then, the functions of H2 with an emphasis on the therapeutic potential and molecular mechanisms involved in the diseases above. We hope this review will provide the future outlook of H2-based therapies for cardiometabolic disease.

scholarly journals TFEB drives PGC-1α expression in adipocytes to protect against diet-induced metabolic dysfunction

2019 ◽  
Vol 12 (606) ◽  
pp. eaau2281 ◽  
Author(s):  
Trent D. Evans ◽  
Xiangyu Zhang ◽  
Se-Jin Jeong ◽  
Anyuan He ◽  
Eric Song ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Metabolic Diseases ◽  
Therapeutic Potential ◽  
Metabolic Effects ◽  
Metabolic Dysfunction ◽  
Helix Loop Helix ◽  
Downstream Effects ◽  
Brown Adipose ◽  
Tissue Browning

TFEB is a basic helix-loop-helix transcription factor that confers protection against metabolic diseases such as atherosclerosis by targeting a network of genes involved in autophagy-lysosomal biogenesis and lipid catabolism. In this study, we sought to characterize the role of TFEB in adipocyte and adipose tissue physiology and evaluate the therapeutic potential of adipocyte-specific TFEB overexpression in obesity. We demonstrated that mice with adipocyte-specific TFEB overexpression (Adipo-TFEB) were protected from diet-induced obesity, insulin resistance, and metabolic sequelae. Adipo-TFEB mice were lean primarily through increased metabolic rate, suggesting a role for adipose tissue browning and enhanced nonshivering thermogenesis in fat. Transcriptional characterization revealed that TFEB targeted genes involved in adipose tissue browning rather than those involved in autophagy. One such gene encoded PGC-1α, an established target of TFEB that promotes adipocyte browning. To dissect the role of PGC-1α in mediating the downstream effects of TFEB overexpression, we generated mice with adipocyte-specific PGC-1α deficiency and TFEB overexpression. Without PGC-1α, the ability of TFEB overexpression to brown adipose tissue and to elicit beneficial metabolic effects was blunted. Overall, these data implicate TFEB as a PGC-1α–dependent regulator of adipocyte browning and suggest its therapeutic potential in treating metabolic disease.

scholarly journals Misconceptions about fructose-containing sugars and their role in the obesity epidemic

2014 ◽  
Vol 27 (1) ◽  
pp. 119-130 ◽  
Author(s):  
Vincent J. van Buul ◽  
Luc Tappy ◽  
Fred J. P. H. Brouns
Keyword(s):  
Body Weight ◽  
Intervention Studies ◽  
Metabolic Diseases ◽  
Body Weight Gain ◽  
Human Subjects ◽  
Metabolic Effects ◽  
Causal Role ◽  
Obesity Epidemic ◽  
Fructose Intake

A causal role of fructose intake in the aetiology of the global obesity epidemic has been proposed in recent years. This proposition, however, rests on controversial interpretations of two distinct lines of research. On one hand, in mechanistic intervention studies, detrimental metabolic effects have been observed after excessive isolated fructose intakes in animals and human subjects. On the other hand, food disappearance data indicate that fructose consumption from added sugars has increased over the past decades and paralleled the increase in obesity. Both lines of research are presently insufficient to demonstrate a causal role of fructose in metabolic diseases, however. Most mechanistic intervention studies were performed on subjects fed large amounts of pure fructose, while fructose is ordinarily ingested together with glucose. The use of food disappearance data does not accurately reflect food consumption, and hence cannot be used as evidence of a causal link between fructose intake and obesity. Based on a thorough review of the literature, we demonstrate that fructose, as commonly consumed in mixed carbohydrate sources, does not exert specific metabolic effects that can account for an increase in body weight. Consequently, public health recommendations and policies aiming at reducing fructose consumption only, without additional diet and lifestyle targets, would be disputable and impractical. Although the available evidence indicates that the consumption of sugar-sweetened beverages is associated with body-weight gain, and it may be that fructose is among the main constituents of these beverages, energy overconsumption is much more important to consider in terms of the obesity epidemic.

scholarly journals Impact of Conventional and Atypical MAPKs on the Development of Metabolic Diseases

Biomolecules ◽  
2020 ◽  
Vol 10 (9) ◽  
pp. 1256
Author(s):  
Toufic Kassouf ◽  
Grzegorz Sumara
Keyword(s):  
Adipose Tissue ◽  
Metabolic Diseases ◽  
Therapeutic Potential ◽  
Cell Metabolism ◽  
Extracellular Signal Regulated Kinase ◽  
Cellular Processes ◽  
Obesity And Diabetes ◽  
Extracellular Signal ◽  
Mediators Of Inflammation ◽  
Mitogen Activated Protein

The family of mitogen-activated protein kinases (MAPKs) consists of fourteen members and has been implicated in regulation of virtually all cellular processes. MAPKs are divided into two groups, conventional and atypical MAPKs. Conventional MAPKs are further classified into four sub-families: extracellular signal-regulated kinases 1/2 (ERK1/2), c-Jun N-terminal kinase (JNK1, 2 and 3), p38 (α, β, γ, δ), and extracellular signal-regulated kinase 5 (ERK5). Four kinases, extracellular signal-regulated kinase 3, 4, and 7 (ERK3, 4 and 7) as well as Nemo-like kinase (NLK) build a group of atypical MAPKs, which are activated by different upstream mechanisms than conventional MAPKs. Early studies identified JNK1/2 and ERK1/2 as well as p38α as a central mediators of inflammation-evoked insulin resistance. These kinases have been also implicated in the development of obesity and diabetes. Recently, other members of conventional MAPKs emerged as important mediators of liver, skeletal muscle, adipose tissue, and pancreatic β-cell metabolism. Moreover, latest studies indicate that atypical members of MAPK family play a central role in the regulation of adipose tissue function. In this review, we summarize early studies on conventional MAPKs as well as recent findings implicating previously ignored members of the MAPK family. Finally, we discuss the therapeutic potential of drugs targeting specific members of the MAPK family.

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