scholarly journals Circulating FGF21 Levels in Human Health and Metabolic Disease

2019 ◽  
Vol 128 (11) ◽  
pp. 752-770 ◽  
Author(s):  
Michaela Keuper ◽  
Hans-Ulrich Häring ◽  
Harald Staiger
Keyword(s):  
Metabolic Disease ◽  
Plasma Lipids ◽  
Therapeutic Potential ◽  
Metabolic Effects ◽  
Fibroblast Growth Factor 21 ◽  
Comprehensive Overview ◽  
Fgf Receptor ◽  
Downstream Signaling ◽  
Beneficial Effects ◽  
Receptor Isoforms

AbstractHuman fibroblast growth factor 21 (FGF21) is primarily produced and secreted by the liver as a hepatokine. This hormone circulates to its target tissues (e. g., brain, adipose tissue), which requires two components, one of the preferred FGF receptor isoforms (FGFR1c and FGFR3c) and the co-factor beta-Klotho (KLB) to trigger downstream signaling pathways. Although targeting FGF21 signaling in humans by analogues and receptor agonists results in beneficial effects, e. g., improvements in plasma lipids and decreased body weight, it failed to recapitulate the improvements in glucose handling shown for many mouse models. FGF21’s role and metabolic effects in mice and its therapeutic potential have extensively been reviewed elsewhere. In this review we focus on circulating FGF21 levels in humans and their associations with disease and clinical parameters, focusing primarily on obesity and obesity-associated diseases such as type-2 diabetes. We provide a comprehensive overview on human circulating FGF21 levels under normal physiology and metabolic disease. We discuss the emerging field of inactivating FGF21 in human blood by fibroblast activation protein (FAP) and its potential clinical implications.

Secretin as a satiation whisperer with the potential to turn into an obesity-curbing knight

Endocrinology ◽  
2021 ◽  
Author(s):  
Katharina Schnabl ◽  
Yongguo Li ◽  
Mueez U-Din ◽  
Martin Klingenspor
Keyword(s):  
Bariatric Surgery ◽  
Body Weight ◽  
Energy Balance ◽  
Food Intake ◽  
Weight Control ◽  
Therapeutic Potential ◽  
Physiological Mechanism ◽  
Gut Hormones ◽  
Metabolic Effects ◽  
Beneficial Effects

Abstract The obesity pandemic requires effective preventative and therapeutic intervention strategies. Successful and sustained obesity treatment is currently limited to bariatric surgery. Modulating the release of gut hormones is considered promising to mimic bariatric surgery with its beneficial effects on food intake, body weight and blood glucose levels. The gut peptide secretin was the first molecule to be termed a hormone; nevertheless, it only recently has been established as a legitimate anorexigenic peptide. In contrast to gut hormones that crosstalk with the brain either directly or by afferent neuronal projections, secretin mediates meal-associated brown fat thermogenesis to induce meal termination, thereby qualifying this physiological mechanism as an attractive, peripheral target for the treatment of obesity. In this perspective, it is of pivotal interest to deepen our yet superficial knowledge on the physiological roles of secretin as well as meal-associated thermogenesis in energy balance and body weight regulation. Of note, the emerging differences between meal-associated thermogenesis and cold-induced thermogenesis must be taken into account. In fact, there is no correlation between these two entities. In addition, the investigation of potential effects of secretin in hedonic-driven food intake, bariatric surgery as well as chronic treatment using suitable application strategies to overcome pharmacokinetic limitations will provide further insight into its potential to influence energy balance. The aim of this article is to review the facts on secretin’s metabolic effects, address prevailing gaps in our knowledge, and provide an overview on the opportunities and challenges of the therapeutic potential of secretin in body weight control.

scholarly journals Fibroblast Growth Factor 21 and the Adaptive Response to Nutritional Challenges

2019 ◽  
Vol 20 (19) ◽  
pp. 4692 ◽  
Author(s):  
Úrsula Martínez-Garza ◽  
Daniel Torres-Oteros ◽  
Alex Yarritu-Gallego ◽  
Pedro F. Marrero ◽  
Diego Haro ◽  
...  
Keyword(s):  
Growth Factor ◽  
Fibroblast Growth Factor ◽  
Metabolic Response ◽  
Therapeutic Potential ◽  
Metabolic Effects ◽  
Fibroblast Growth Factor 21 ◽  
Signal Pathways ◽  
Fibroblast Growth ◽  
The Impact

The Fibroblast Growth Factor 21 (FGF21) is considered an attractive therapeutic target for obesity and obesity-related disorders due to its beneficial effects in lipid and carbohydrate metabolism. FGF21 response is essential under stressful conditions and its metabolic effects depend on the inducer factor or stress condition. FGF21 seems to be the key signal which communicates and coordinates the metabolic response to reverse different nutritional stresses and restores the metabolic homeostasis. This review is focused on describing individually the FGF21-dependent metabolic response activated by some of the most common nutritional challenges, the signal pathways triggering this response, and the impact of this response on global homeostasis. We consider that this is essential knowledge to identify the potential role of FGF21 in the onset and progression of some of the most prevalent metabolic pathologies and to understand the potential of FGF21 as a target for these diseases. After this review, we conclude that more research is needed to understand the mechanisms underlying the role of FGF21 in macronutrient preference and food intake behavior, but also in β-klotho regulation and the activity of the fibroblast activation protein (FAP) to uncover its therapeutic potential as a way to increase the FGF21 signaling.

scholarly journals Ketogenic Diet as Medical Nutrition Therapy

2019 ◽  
Vol 7 (02) ◽  
pp. 73-76
Author(s):  
Dharini Krishnan ◽  
Chetan Mehndiratta ◽  
Tanmay Agrawal
Keyword(s):  
Ketogenic Diet ◽  
Therapeutic Potential ◽  
Nutrition Therapy ◽  
The Body ◽  
Metabolic Effects ◽  
Medical Nutrition Therapy ◽  
Moderate Amount ◽  
Beneficial Effects ◽  
Ketogenic Diets ◽  
Medical Nutrition

AbstractMedical nutrition therapy is a therapeutic approach to treat medical conditions and their associated symptoms via using a specifically tailored diet devised under the supervision of a doctor and a registered dietitian or nutrition professional. Ketogenic diet primarily consists of the high amount of fats, a moderate amount of proteins, and very low carbohydrates. It is known to stimulate the metabolic effects of starvation by forcing the body to use primarily fat as a fuel source. Ketogenic diet was developed in the 1920s. Nowadays, it is gaining considerable attention as a potential weight-loss strategy because of the low-carb diet. However, it is being considered for use in several diseases/disorders also because of the beneficial effects on the metabolic health and nervous system. This review revisits the therapeutic potential of ketogenic diets in many pathological conditions and its role as a medical nutrition therapy. It also talks about the ill effects that the keto diet can have in case of self-usage and monitoring.

scholarly journals Role of exercise-induced hepatokines in metabolic disorders

2019 ◽  
Vol 317 (1) ◽  
pp. E11-E24 ◽  
Author(s):  
Gaël Ennequin ◽  
Pascal Sirvent ◽  
Martin Whitham
Keyword(s):  
Metabolic Disease ◽  
Metabolic Disorders ◽  
Molecular Mechanisms ◽  
Acute Exercise ◽  
Whole Body ◽  
Fibroblast Growth Factor 21 ◽  
Beneficial Effects ◽  
Future Challenges ◽  
Exercise Induced

The health-promoting effects of physical activity to prevent and treat metabolic disorders are numerous. However, the underlying molecular mechanisms are not yet completely deciphered. In recent years, studies have referred to the liver as an endocrine organ, since it releases specific proteins called hepatokines. Some of these hepatokines are involved in whole body metabolic homeostasis and are theorized to participate in the development of metabolic disease. In this regard, the present review describes the role of Fibroblast Growth Factor 21, Fetuin-A, Angiopoietin-like protein 4, and Follistatin in metabolic disease and their production in response to acute exercise. Also, we discuss the potential role of hepatokines in mediating the beneficial effects of regular exercise and the future challenges to the discovery of new exercise-induced hepatokines.

Garlic and cardioprotection: insights into the molecular mechanisms

2013 ◽  
Vol 91 (6) ◽  
pp. 448-458 ◽  
Author(s):  
Tarak Nath Khatua ◽  
Ramu Adela ◽  
Sanjay K. Banerjee
Keyword(s):  
Molecular Mechanisms ◽  
Plasma Lipids ◽  
Ischemia Reperfusion Injury ◽  
Therapeutic Potential ◽  
Wide Spectrum ◽  
Ischemia Reperfusion ◽  
Cardioprotective Effect ◽  
Cardiovascular Disorders ◽  
Histone Deacetylase Inhibition ◽  
Beneficial Effects

Garlic is widely recognized for its immense therapeutic potential. Garlic has been shown to exert its beneficial effects against a wide spectrum of diseases, including cancer, diabetes, and microbial infections, as well as immunological and cardiovascular disorders. Most of the research on garlic has indicated that garlic and its active compounds are effective in reducing cardiovascular and metabolic risk by normalizing abnormal plasma lipids, oxidized low density lipoproteins, abnormal platelet aggregation, high blood pressure, and cardiac injury. Some of the beneficial effects of dietary garlic against cardiovascular disorders are mediated via the generation of hydrogen sulfide and nitric oxide in cardiomyocytes and endothelial cells. Garlic has the potential to protect the heart against myocardial infarction, doxorubicin-induced cardiotoxicity, arrhythmia, hypertrophy, and ischemia–reperfusion injury. The induction of cardiac endogenous antioxidants and the reduction of lipid peroxidation by garlic has been reported by several different groups. Other mechanisms, such as regulating ion channels, modulating Akt signaling pathways, histone deacetylase inhibition, and cytochrome P450 inhibition, could be responsible for the cardioprotective effect of garlic. Although several mechanisms have been identified for the cardioprotective effect of garlic, there is a need for further research to identify the specific molecular mechanism of cardioprotection in different cardiac diseases.

Dehydroepiandrosterone (DHEA) and its Sulphate (DHEAS) in Alzheimer’s Disease

2020 ◽  
Vol 17 (2) ◽  
pp. 141-157 ◽  
Author(s):  
Dubravka S. Strac ◽  
Marcela Konjevod ◽  
Matea N. Perkovic ◽  
Lucija Tudor ◽  
Gordana N. Erjavec ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Large Scale ◽  
Therapeutic Potential ◽  
Relevant Literature ◽  
Comprehensive Overview ◽  
Brain Functions ◽  
Specific Effects ◽  
And Behavior

Background: Neurosteroids Dehydroepiandrosterone (DHEA) and Dehydroepiandrosterone Sulphate (DHEAS) are involved in many important brain functions, including neuronal plasticity and survival, cognition and behavior, demonstrating preventive and therapeutic potential in different neuropsychiatric and neurodegenerative disorders, including Alzheimer’s disease. Objective: The aim of the article was to provide a comprehensive overview of the literature on the involvement of DHEA and DHEAS in Alzheimer’s disease. Method: PubMed and MEDLINE databases were searched for relevant literature. The articles were selected considering their titles and abstracts. In the selected full texts, lists of references were searched manually for additional articles. Results: We performed a systematic review of the studies investigating the role of DHEA and DHEAS in various in vitro and animal models, as well as in patients with Alzheimer’s disease, and provided a comprehensive discussion on their potential preventive and therapeutic applications. Conclusion: Despite mixed results, the findings of various preclinical studies are generally supportive of the involvement of DHEA and DHEAS in the pathophysiology of Alzheimer’s disease, showing some promise for potential benefits of these neurosteroids in the prevention and treatment. However, so far small clinical trials brought little evidence to support their therapy in AD. Therefore, large-scale human studies are needed to elucidate the specific effects of DHEA and DHEAS and their mechanisms of action, prior to their applications in clinical practice.

scholarly journals Beneficial Effects of Akkermansia muciniphila Are Not Associated with Major Changes in the Circulating Endocannabinoidome but Linked to Higher Mono-Palmitoyl-Glycerol Levels as New PPARα Agonists

Cells ◽  
2021 ◽  
Vol 10 (1) ◽  
pp. 185
Author(s):  
Clara Depommier ◽  
Rosa Maria Vitale ◽  
Fabio Arturo Iannotti ◽  
Cristoforo Silvestri ◽  
Nicolas Flamand ◽  
...  
Keyword(s):  
Metabolic Syndrome ◽  
Univariate Analysis ◽  
Metabolic Effects ◽  
Peroxisome Proliferator ◽  
Peroxisome Proliferator Activated Receptor ◽  
Akkermansia Muciniphila ◽  
Beneficial Effects ◽  
Daily Ingestion ◽  
Before And After ◽  
Palmitoyl Glycerol

Akkermansia muciniphila is considered as one of the next-generation beneficial bacteria in the context of obesity and associated metabolic disorders. Although a first proof-of-concept of its beneficial effects has been established in the context of metabolic syndrome in humans, mechanisms are not yet fully understood. This study aimed at deciphering whether the bacterium exerts its beneficial properties through the modulation of the endocannabinoidome (eCBome). Circulating levels of 25 endogenous endocannabinoid-related lipids were quantified by liquid chromatography with tandem mass spectrometry (LC-MS/MS) in the plasma of overweight or obese individuals before and after a 3 months intervention consisting of the daily ingestion of either alive or pasteurized A. muciniphila. Results from multivariate analyses suggested that the beneficial effects of A. muciniphila were not linked to an overall modification of the eCBome. However, subsequent univariate analysis showed that the decrease in 1-Palmitoyl-glycerol (1-PG) and 2-Palmitoyl-glycerol (2-PG), two eCBome lipids, observed in the placebo group was significantly counteracted by the alive bacterium, and to a lower extent by the pasteurized form. We also discovered that 1- and 2-PG are endogenous activators of peroxisome proliferator-activated receptor alpha (PPARα). We hypothesize that PPARα activation by mono-palmitoyl-glycerols may underlie part of the beneficial metabolic effects induced by A. muciniphila in human metabolic syndrome.

scholarly journals Targeting necroptosis as therapeutic potential in chronic myocardial infarction

2021 ◽  
Vol 28 (1) ◽  
Author(s):  
Chanon Piamsiri ◽  
Chayodom Maneechote ◽  
Natthaphat Siri-Angkul ◽  
Siriporn C. Chattipakorn ◽  
Nipon Chattipakorn
Keyword(s):  
Myocardial Infarction ◽  
Therapeutic Potential ◽  
Coronary Perfusion ◽  
Beneficial Effects ◽  
Cell Death Pathways ◽  
Threatening Condition ◽  
Underlying Mechanisms ◽  
Novel Therapeutic Strategies

AbstractCardiovascular diseases (CVDs) are considered the predominant cause of morbidity and mortality globally. Of these, myocardial infarction (MI) is the most common cause of CVD mortality. MI is a life-threatening condition which occurs when coronary perfusion is interrupted leading to cardiomyocyte death. Subsequent to MI, consequences include adverse cardiac remodeling and cardiac dysfunction mainly contribute to the development of heart failure (HF). It has been shown that loss of functional cardiomyocytes in MI-induced HF are associated with several cell death pathways, in particular necroptosis. Although the entire mechanism underlying necroptosis in MI progression is still not widely recognized, some recent studies have reported beneficial effects of necroptosis inhibitors on cell viability and cardiac function in chronic MI models. Therefore, extensive investigation into the necroptosis signaling pathway is indicated for further study. This article comprehensively reviews the context of the underlying mechanisms of necroptosis in chronic MI-induced HF in in vitro, in vivo and clinical studies. These findings could inform ways of developing novel therapeutic strategies to improve the clinical outcomes in MI patients from this point forward.

Brain angiotensin system: a new promise in the management of epilepsy?

2021 ◽  
Vol 135 (6) ◽  
pp. 725-730
Author(s):  
Alberto Javier Ramos
Keyword(s):  
Therapeutic Potential ◽  
Renin Angiotensin System ◽  
B Cell Lymphoma ◽  
Ang Ii ◽  
Angiotensin System ◽  
Beneficial Effects ◽  
System A ◽  
Pilocarpine Model ◽  
Animal Models Of Epilepsy ◽  
Future Work

Abstract Epilepsy is a highly prevalent neurological disease and anti-epileptic drugs (AED) are almost the unique clinical treatment option. A disbalanced brain renin–angiotensin system (RAS) has been proposed in epilepsy and several reports have shown that angiotensin II (Ang II) receptor-1 (ATR1) activation is pro-inflammatory and pro-epileptogenic. In agreement, ATR1 blockage with the repurposed drug losartan has shown benefits in animal models of epilepsy. Processing of Ang II by ACE2 enzyme renders Ang-(1-7), a metabolite that activates the mitochondrial assembly (Mas) receptor (MasR) pathway. MasR activation presents beneficial effects, facilitating vasodilatation, increasing anti-inflammatory and antioxidative responses. In a recent paper published in Clinical Science, Gomes and colleagues (Clin. Sci. (Lond.) (2020) 134, 2263–2277) performed intracerebroventricular (icv) infusion of Ang-(1-7) in animals subjected to the pilocarpine model of epilepsy, starting after the first spontaneous motor seizure (SMS). They showed that this approach reduced the frequency of SMS, restored animal anxiety, increased exploration, and augmented the hippocampal expression of protective catalase enzyme and antiapoptotic protein B-cell lymphoma 2 (Bcl-2). Interestingly, but surprisingly, Gomes and colleagues showed that MasR expression and mTor activity were reduced in the hippocampus of the epileptic Ang-(1-7) treated animals. These results show that Ang-(1-7) administration could represent a new avenue for developing strategies for the management of epilepsy in clinical settings. However, future work is necessary to evaluate the levels of RAS metabolites and the activity of key enzymes in these experimental interventions to completely understand the therapeutic potential of the brain RAS manipulation in epilepsy.

From mesenchymal stem cells and stromal cells - from bench to bedside

2019 ◽  
Vol 1 (1) ◽  
pp. 36-39
Author(s):  
Bernd Giebel ◽  
Verena Börger ◽  
Mario Gimona ◽  
Eva Rohde
Keyword(s):  
Stem Cells ◽  
Clinical Trials ◽  
Mesenchymal Stem Cells ◽  
Stromal Cells ◽  
Therapeutic Agent ◽  
Therapeutic Potential ◽  
Therapeutic Effects ◽  
Cell Replacement ◽  
Beneficial Effects ◽  
Promising Tool

Human mesenchymal stem/stromal cells (MSCs) represent a promising tool in regenerative medicine. Until now, almost one thousand NIH-registered clinical trials investigated their immunomodulatory and pro-regenerative therapeutic potential in various diseases. Despite controversial reports regarding the efficacy of MSC-treatments, MSCs appear to exert their beneficial effects in a paracrine manner rather than by cell replacement. In this context, extracellular vesicles (EVs), such as exosomes and microvesicles, seem to induce the MSCs’ therapeutic effects. Here, we briefly illustrate the potential of MSC-EVs as therapeutic agent of the future.

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