Novel Non-invasive Approaches to the Treatment of Obesity: From Pharmacotherapy to Gene Therapy

2021 ◽  
Author(s):  
Angeliki M Angelidi ◽  
Matthew J Belanger ◽  
Alexander Kokkinos ◽  
Chrysi C Koliaki ◽  
Christos S Mantzoros
Keyword(s):  
Gene Therapy ◽  
Drug Targets ◽  
Energy Homeostasis ◽  
Treatment Options ◽  
Gastrointestinal Hormones ◽  
Interindividual Variation ◽  
Obesity Epidemic ◽  
Treatment Of Obesity ◽  
Underlying Mechanisms ◽  
Novel Therapeutic Strategies

Abstract Recent insights into the pathophysiologic underlying mechanisms of obesity have led to the discovery of several promising drug targets and novel therapeutic strategies to address the global obesity epidemic and its comorbidities. Current pharmacologic options for obesity management are largely limited in number and of modest efficacy/safety profile. Therefore, the need for safe and more efficacious new agents is urgent. Drugs which are currently under investigation modulate targets across a broad range of systems and tissues, including the central nervous system, gastrointestinal hormones, adipose tissue, kidney, liver, and skeletal muscle. Beyond pharmacotherapeutics, other potential antiobesity strategies are being explored, including novel drug delivery systems, vaccines, modulation of the gut microbiome, and gene therapy. The present review summarizes the pathophysiology of energy homeostasis, and highlights pathways being explored in the effort to develop novel antiobesity medications and interventions but does not cover devices and bariatric methods. Emerging pharmacologic agents and alternative approaches targeting these pathways and relevant research in both animals and humans are presented in detail. Special emphasis is given to treatment options at the end of the development pipeline and closer to the clinic, i.e., compounds that have a higher chance to be added to our therapeutic armamentarium in the near future. Ultimately, advancements in our understanding of the pathophysiology and interindividual variation of obesity may lead to multimodal and personalized approaches to obesity treatment that will result in safe, effective and sustainable weight loss until the root causes of the problem are identified and addressed.

A Review of Past and Present Weight Loss Strategies and the Potential Role of Bariatric Arterial Embolization

2020 ◽  
Vol 04 (02) ◽  
pp. 195-205
Author(s):  
Varun R. Danda ◽  
Christopher R. Bailey ◽  
Clifford R. Weiss
Keyword(s):  
Weight Loss ◽  
Treatment Options ◽  
Arterial Embolization ◽  
Health Concern ◽  
Lifestyle Modifications ◽  
Obesity Epidemic ◽  
Cost Treatment ◽  
Clinically Significant ◽  
Treatment Of Obesity ◽  
Bariatric Embolization

AbstractThe obesity epidemic is a growing public health concern that has a severe effect on the health care system with significant morbidity, mortality, and cost. Treatment options for obesity include lifestyle modifications, pharmacotherapy, and bariatric surgery. Newer, less-invasive therapies including endoscopic bariatric procedures have been developed in recent years to fill the treatment gap that exists between noninvasive approaches and surgery. Bariatric artery embolization (BAE) is a novel minimally invasive endovascular procedure that has been developed to treat obesity. Recent evidence has suggested that bariatric embolization is well tolerated and can induce clinically significant weight loss through a hormonally mediated mechanism. This article will review existing preclinical and clinical data, and explore future directions of the endovascular treatment of obesity.

scholarly journals Exercise and High-Fat Diet in Obesity: Functional Genomics Perspectives of Two Energy Homeostasis Pillars

Genes ◽  
2020 ◽  
Vol 11 (8) ◽  
pp. 875 ◽  
Author(s):  
Abdelaziz Ghanemi ◽  
Aicha Melouane ◽  
Mayumi Yoshioka ◽  
Jonny St-Amand
Keyword(s):  
Functional Genomics ◽  
Energy Homeostasis ◽  
Molecular Mechanisms ◽  
High Fat ◽  
Pharmacological Agents ◽  
Adequate Diet ◽  
Obesity Epidemic ◽  
Underlying Mechanisms ◽  
New Applications ◽  
Therapeutic Alternatives

The heavy impact of obesity on both the population general health and the economy makes clarifying the underlying mechanisms, identifying pharmacological targets, and developing efficient therapies for obesity of high importance. The main struggle facing obesity research is that the underlying mechanistic pathways are yet to be fully revealed. This limits both our understanding of pathogenesis and therapeutic progress toward treating the obesity epidemic. The current anti-obesity approaches are mainly a controlled diet and exercise which could have limitations. For instance, the “classical” anti-obesity approach of exercise might not be practical for patients suffering from disabilities that prevent them from routine exercise. Therefore, therapeutic alternatives are urgently required. Within this context, pharmacological agents could be relatively efficient in association to an adequate diet that remains the most efficient approach in such situation. Herein, we put a spotlight on potential therapeutic targets for obesity identified following differential genes expression-based studies aiming to find genes that are differentially expressed under diverse conditions depending on physical activity and diet (mainly high-fat), two key factors influencing obesity development and prognosis. Such functional genomics approaches contribute to elucidate the molecular mechanisms that both control obesity development and switch the genetic, biochemical, and metabolic pathways toward a specific energy balance phenotype. It is important to clarify that by “gene-related pathways”, we refer to genes, the corresponding proteins and their potential receptors, the enzymes and molecules within both the cells in the intercellular space, that are related to the activation, the regulation, or the inactivation of the gene or its corresponding protein or pathways. We believe that this emerging area of functional genomics-related exploration will not only lead to novel mechanisms but also new applications and implications along with a new generation of treatments for obesity and the related metabolic disorders especially with the modern advances in pharmacological drug targeting and functional genomics techniques.

scholarly journals Sir David Cuthbertson Medal Lecture Bariatric surgery as a model to study appetite control

2009 ◽  
Vol 68 (3) ◽  
pp. 227-233 ◽  
Author(s):  
Marco Bueter ◽  
Carel W. le Roux
Keyword(s):  
Bariatric Surgery ◽  
Peptide Yy ◽  
Gastrointestinal Hormones ◽  
Gut Hormones ◽  
Gastric Inhibitory Polypeptide ◽  
Appetite Regulation ◽  
Appetite Control ◽  
Obesity Epidemic ◽  
Glucagon Like Peptide 1 ◽  
Underlying Mechanisms

The obesity epidemic and its associated morbidity and mortality have led to major research efforts to identify mechanisms that regulate appetite. Gut hormones have recently been found to be an important element in appetite regulation as a result of the signals from the periphery to the brain. Candidate hormones include ghrelin, peptide YY, glucagon-like peptide-1 and gastric inhibitory polypeptide, all of which are currently being investigated as potential obesity treatments. Bariatric surgery is currently the most effective therapy for substantial and sustained weight loss. Understanding how levels of gut hormones are modulated by such procedures has greatly contributed to the comprehension of the underlying mechanisms of appetite and obesity. The present paper is a review of how appetite and levels of gastrointestinal hormones are altered after bariatric surgery. Basic principles of common bariatric procedures and potential mechanisms for appetite regulation by gut hormones are also addressed.

scholarly journals Molecular and Cellular Mechanisms of Metformin in Cervical Cancer

Cancers ◽  
2021 ◽  
Vol 13 (11) ◽  
pp. 2545
Author(s):  
Ya-Hui Chen ◽  
Po-Hui Wang ◽  
Pei-Ni Chen ◽  
Shun-Fa Yang ◽  
Yi-Hsuan Hsiao
Keyword(s):  
Cervical Cancer ◽  
Potential Role ◽  
Treatment Options ◽  
Cellular Mechanisms ◽  
Anticancer Effects ◽  
Clinical Benefits ◽  
Underlying Mechanisms

Cervical cancer is one of the major gynecologic malignancies worldwide. Treatment options include chemotherapy, surgical resection, radiotherapy, or a combination of these treatments; however, relapse and recurrence may occur, and the outcome may not be favorable. Metformin is an established, safe, well-tolerated drug used in the treatment of type 2 diabetes; it can be safely combined with other antidiabetic agents. Diabetes, possibly associated with an increased site-specific cancer risk, may relate to the progression or initiation of specific types of cancer. The potential effects of metformin in terms of cancer prevention and therapy have been widely studied, and a number of studies have indicated its potential role in cancer treatment. The most frequently proposed mechanism underlying the diabetes–cancer association is insulin resistance, which leads to secondary hyperinsulinemia; furthermore, insulin may exert mitogenic effects through the insulin-like growth factor 1 (IGF-1) receptor, and hyperglycemia may worsen carcinogenesis through the induction of oxidative stress. Evidence has suggested clinical benefits of metformin in the treatment of gynecologic cancers. Combining current anticancer drugs with metformin may increase their efficacy and diminish adverse drug reactions. Accumulating evidence is indicating that metformin exerts anticancer effects alone or in combination with other agents in cervical cancer in vitro and in vivo. Metformin might thus serve as an adjunct therapeutic agent for cervical cancer. Here, we reviewed the potential anticancer effects of metformin against cervical cancer and discussed possible underlying mechanisms.

scholarly journals 4E Interacting Protein as a Potential Novel Drug Target for Nucleoside Analogues in Trypanosoma Brucei

2021 ◽  
Vol 9 (4) ◽  
pp. 826
Author(s):  
Dorien Mabille ◽  
Camila Cardoso Santos ◽  
Rik Hendrickx ◽  
Mathieu Claes ◽  
Peter Takac ◽  
...  
Keyword(s):  
Mode Of Action ◽  
Drug Target ◽  
Drug Targets ◽  
De Novo ◽  
Treatment Options ◽  
Adenosine Kinase ◽  
Nucleoside Analogues ◽  
Purine Salvage ◽  
Interacting Protein ◽  
Novel Drug

Human African trypanosomiasis is a neglected parasitic disease for which the current treatment options are quite limited. Trypanosomes are not able to synthesize purines de novo and thus solely depend on purine salvage from the host environment. This characteristic makes players of the purine salvage pathway putative drug targets. The activity of known nucleoside analogues such as tubercidin and cordycepin led to the development of a series of C7-substituted nucleoside analogues. Here, we use RNA interference (RNAi) libraries to gain insight into the mode-of-action of these novel nucleoside analogues. Whole-genome RNAi screening revealed the involvement of adenosine kinase and 4E interacting protein into the mode-of-action of certain antitrypanosomal nucleoside analogues. Using RNAi lines and gene-deficient parasites, 4E interacting protein was found to be essential for parasite growth and infectivity in the vertebrate host. The essential nature of this gene product and involvement in the activity of certain nucleoside analogues indicates that it represents a potential novel drug target.

scholarly journals Propolis Extract and Chitosan Improve Health of Nosema ceranae Infected Giant Honey Bees, Apis dorsata Fabricius, 1793

Pathogens ◽  
2021 ◽  
Vol 10 (7) ◽  
pp. 785
Author(s):  
Sanchai Naree ◽  
Rujira Ponkit ◽  
Evada Chotiaroonrat ◽  
Christopher L. Mayack ◽  
Guntima Suwannapong
Keyword(s):  
Honey Bees ◽  
Treatment Options ◽  
Survival Rates ◽  
Nosema Ceranae ◽  
Apis Dorsata ◽  
Propolis Extract ◽  
Bee Health ◽  
Honey Bee Health ◽  
Underlying Mechanisms ◽  
Honey Solution

Nosema ceranae is a large contributing factor to the most recent decline in honey bee health worldwide. Developing new alternative treatments against N. ceranae is particularly pressing because there are few treatment options available and therefore the risk of increased antibiotic resistance is quite high. Recently, natural products have demonstrated to be a promising avenue for finding new effective treatments against N. ceranae. We evaluated the effects of propolis extract of stingless bee, Tetrigona apicalis and chito-oligosaccharide (COS) on giant honey bees, Apis dorsata, experimentally infected with N. ceranae to determine if these treatments could improve the health of the infected individuals. Newly emerged Nosema-free bees were individually inoculated with 106N. ceranae spores per bee. We fed infected and control bees the following treatments consisting of 0%, 50%, propolis extracts, 0 ppm and 0.5 ppm COS in honey solution (w/v). Propolis extracts and COS caused a significant increase in trehalose levels in hemolymph, protein contents, survival rates and acini diameters of the hypopharyngeal glands in infected bees. Our results suggest that propolis and COS could improve the health of infected bees. Further research is needed to determine the underlying mechanisms responsible for the improved health of the infected bees.

scholarly journals Targeting Autophagy to Counteract Obesity-Associated Oxidative Stress

Antioxidants ◽  
2021 ◽  
Vol 10 (1) ◽  
pp. 102
Author(s):  
Federico Pietrocola ◽  
José Manuel Bravo-San Pedro
Keyword(s):  
Oxidative Stress ◽  
Oxygen Species ◽  
Alcoholic Fatty Liver ◽  
Redox Biology ◽  
Obesity Therapy ◽  
Treatment Of Obesity ◽  
Novel Therapeutic Strategies ◽  
Alcoholic Fatty Liver Disease ◽  
Shed Light

Reactive oxygen species (ROS) operate as key regulators of cellular homeostasis within a physiological range of concentrations, yet they turn into cytotoxic entities when their levels exceed a threshold limit. Accordingly, ROS are an important etiological cue for obesity, which in turn represents a major risk factor for multiple diseases, including diabetes, cardiovascular disorders, non-alcoholic fatty liver disease, and cancer. Therefore, the implementation of novel therapeutic strategies to improve the obese phenotype by targeting oxidative stress is of great interest for the scientific community. To this end, it is of high importance to shed light on the mechanisms through which cells curtail ROS production or limit their toxic effects, in order to harness them in anti-obesity therapy. In this review, we specifically discuss the role of autophagy in redox biology, focusing on its implication in the pathogenesis of obesity. Because autophagy is specifically triggered in response to redox imbalance as a quintessential cytoprotective mechanism, maneuvers based on the activation of autophagy hold promises of efficacy for the prevention and treatment of obesity and obesity-related morbidities.

scholarly journals The Function of Gastrointestinal Hormones in Obesity—Implications for the Regulation of Energy Intake

Nutrients ◽  
2021 ◽  
Vol 13 (6) ◽  
pp. 1839
Author(s):  
Mona Farhadipour ◽  
Inge Depoortere
Keyword(s):  
Energy Homeostasis ◽  
Gastric Bypass Surgery ◽  
Gastrointestinal Hormones ◽  
Enteroendocrine Cells ◽  
Hormone Balance ◽  
Gut Hormone ◽  
Control Food ◽  
Induce Weight Loss ◽  
Novel Strategy ◽  
Control Food Intake

The global burden of obesity and the challenges of prevention prompted researchers to investigate the mechanisms that control food intake. Food ingestion triggers several physiological responses in the digestive system, including the release of gastrointestinal hormones from enteroendocrine cells that are involved in appetite signalling. Disturbed regulation of gut hormone release may affect energy homeostasis and contribute to obesity. In this review, we summarize the changes that occur in the gut hormone balance during the pre- and postprandial state in obesity and the alterations in the diurnal dynamics of their plasma levels. We further discuss how obesity may affect nutrient sensors on enteroendocrine cells that sense the luminal content and provoke alterations in their secretory profile. Gastric bypass surgery elicits one of the most favorable metabolic outcomes in obese patients. We summarize the effect of different strategies to induce weight loss on gut enteroendocrine function. Although the mechanisms underlying obesity are not fully understood, restoring the gut hormone balance in obesity by targeting nutrient sensors or by combination therapy with gut peptide mimetics represents a novel strategy to ameliorate obesity.

scholarly journals In search of an ideal drug for safer treatment of obesity: The false promise of pseudoephedrine

2021 ◽  
Author(s):  
Antonio Munafò ◽  
Stefano Frara ◽  
Norberto Perico ◽  
Rosaria Di Mauro ◽  
Monica Cortinovis ◽  
...  
Keyword(s):  
Adverse Events ◽  
Treatment Options ◽  
Public Health Problem ◽  
Cardiovascular Death ◽  
Regulation Of Transcription ◽  
Major Public Health Problem ◽  
Obese Patients ◽  
Ephedra Sinica ◽  
The Central Nervous System ◽  
Treatment Of Obesity

AbstractObesity is a major public health problem worldwide. Only relatively few treatment options are, at present, available for the management of obese patients. Furthermore, treatment of obesity is affected by the widespread misuse of drugs and food supplements. Ephedra sinica is an old medicinal herb, commonly used in the treatment of respiratory tract diseases. Ephedra species contain several alkaloids, including pseudoephedrine, notably endowed with indirect sympathomimetic pharmacodynamic properties. The anorexigenic effect of pseudoephedrine is attributable primarily to the inhibition of neurons located in the hypothalamic paraventricular nucleus (PVN), mediating satiety stimuli. Pseudoephedrine influences lipolysis and thermogenesis through interaction with β3 adrenergic receptors and reduces fat accumulation through down-regulation of transcription factors related to lipogenesis. However, its use is associated with adverse events that involve to a large extent the cardiovascular and the central nervous system. Adverse events of pseudoephedrine also affect the eye, the intestine, and the skin, and, of relevance, sudden cardiovascular death related to dietary supplements containing Ephedra alkaloids has also been reported. In light of the limited availability of clinical data on pseudoephedrine in obesity, along with its significantly unbalanced risk/benefit profile, as well as of the psychophysical susceptibility of obese patients, it appears reasonable to preclude the prescription of pseudoephedrine in obese patients of any order and degree.

Management of Plantar Keratodermas

2017 ◽  
Vol 107 (5) ◽  
pp. 428-435 ◽  
Author(s):  
Rebecca M. Porter ◽  
Albert A. Bravo ◽  
Frances J.D. Smith
Keyword(s):  
Gene Therapy ◽  
Salicylic Acid ◽  
Alternative Treatment ◽  
Autosomal Dominant ◽  
Treatment Options ◽  
Clinical Manifestations ◽  
Specific Treatment ◽  
Inherited Mutations ◽  
Pachyonychia Congenita

Plantar keratodermas can arise due to a variety of genetically inherited mutations. The need to distinguish between different plantar keratoderma disorders is becoming increasingly apparent because there is evidence that they do not respond identically to treatment. Diagnosis can be aided by observation of other clinical manifestations, such as palmar keratoderma, more widespread hyperkeratosis of the epidermis, hair and nail dystrophies, or erythroderma. However, there are frequent cases of plantar keratoderma that occur in isolation. This review focuses on the rare autosomal dominant keratin disorder pachyonychia congenita, which presents with particularly painful plantar keratoderma for which there is no specific treatment. Typically, patients regularly trim/pare/file/grind their calluses and file/grind/clip their nails. Topical agents, including keratolytics (eg, salicylic acid, urea) and moisturizers, can provide limited benefit by softening the skin. For some patients, retinoids help to thin calluses but may lead to increased pain. This finding has stimulated a drive for alternative treatment options, from gene therapy to alternative nongenetic methods that focus on novel findings regarding the pathogenesis of pachyonychia congenita and the function of the underlying genes.

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