scholarly journals MECHANISMS IN ENDOCRINOLOGY: Update on treatments for patients with genetic obesity

2020 ◽  
Vol 183 (5) ◽  
pp. R149-R166
Author(s):  
C Poitou ◽  
H Mosbah ◽  
K Clément
Keyword(s):  
Complex Disease ◽  
Severe Obesity ◽  
Multidisciplinary Care ◽  
Epigenetic Factors ◽  
Genetic Obesity ◽  
Molecular Alterations ◽  
Syndromic Obesity ◽  
Innovative Therapies ◽  
Uncertain Outcomes ◽  
Access To Food

Obesity, defined by an excess of body fat impacting on health, is a complex disease resulting from the interaction between many genetic/epigenetic factors and environmental triggers. For some clinical situations with severe obesity, it has been possible to classify these obesity forms according to the molecular alterations. These include: (i) syndromic obesity, which associates severe early-onset obesity with neurodevelopmental disorders and/or polymalformative syndrome and (ii) non-syndromic monogenic obesity, due to gene variants most often located in the leptin-melanocortin pathway. In addition to severe obesity, patients affected by these diseases display complex somatic conditions, eventually including obesity comorbidities, neuropsychological and psychiatric disorders. These conditions render the clinical management of these patients particularly challenging. Patients’ early diagnosis is critical to allow specialized and multidisciplinary care, with a necessary interaction between the health and social sectors. Up to now, the management of genetic obesity was only based, above all, on controlling the patient's environment, which involves limiting access to food, ensuring a reassuring daily eating environment that limits impulsiveness, and the practice of adapted, supported, and supervised physical activity. Bariatric surgery has also been undertaken in genetic obesity cases with uncertain outcomes. The context is rapidly changing, as new innovative therapies are currently being tested both for syndromic and monogenic forms of obesity. This review focuses on care management and new therapeutic opportunities in genetic obesity, including the use of the melanocortin 4 agonist, setmelanotide. The results from ongoing trials will hopefully pave the way to a future precision medicine approach for genetic obesity.

scholarly journals Evaluation and Management of Early Onset Genetic Obesity in Childhood

2021 ◽  
Author(s):  
Sonali Malhotra ◽  
Ramya Sivasubramanian ◽  
Gitanjali Srivastava
Keyword(s):  
Severe Obesity ◽  
Wide Spectrum ◽  
Genetic Disorders ◽  
Treatment Strategies ◽  
Multidisciplinary Care ◽  
The United States ◽  
Management Options ◽  
Syndromic Obesity ◽  
Investigational Drugs ◽  
Surgical Options

AbstractOne in five children and adolescents in the United States are diagnosed with obesity and nearly 6% of them are being classified under the severe obesity category. With over 7% of severe obesity being attributed to genetic disorders, in this review we aim to focus on monogenic and syndromic obesity: its etiology, wide spectrum of clinical presentation, criticalness of early identification, and limited management options. Advanced genetic testing methods including microarray and whole genome sequencing are imperative to identify the spectrum of mutations and develop targeted treatment strategies including personalized multidisciplinary care, use of investigational drugs, and explore surgical options in this unique subset of severe pediatric obesity.

scholarly journals Genetic and Epigenetic Modifiers of Alcoholic Liver Disease

2018 ◽  
Vol 19 (12) ◽  
pp. 3857 ◽  
Author(s):  
Marica Meroni ◽  
Miriam Longo ◽  
Raffaela Rametta ◽  
Paola Dongiovanni
Keyword(s):  
Liver Disease ◽  
Alcohol Consumption ◽  
Alcoholic Liver Disease ◽  
Complex Disease ◽  
Wide Spectrum ◽  
Association Studies ◽  
Phenotypic Variability ◽  
Genome Wide Association Studies ◽  
Epigenetic Factors ◽  
Excessive Alcohol Consumption

Alcoholic liver disease (ALD), a disorder caused by excessive alcohol consumption is a global health issue. More than two billion people consume alcohol in the world and about 75 million are classified as having alcohol disorders. ALD embraces a wide spectrum of hepatic lesions including steatosis, alcoholic steatohepatitis (ASH), fibrosis, cirrhosis, and hepatocellular carcinoma (HCC). ALD is a complex disease where environmental, genetic, and epigenetic factors contribute to its pathogenesis and progression. The severity of alcohol-induced liver disease depends on the amount, method of usage and duration of alcohol consumption as well as on age, gender, presence of obesity, and genetic susceptibility. Genome-wide association studies and candidate gene studies have identified genetic modifiers of ALD that can be exploited as non-invasive biomarkers, but which do not completely explain the phenotypic variability. Indeed, ALD development and progression is also modulated by epigenetic factors. The premise of this review is to discuss the role of genetic variants and epigenetic modifications, with particular attention being paid to microRNAs, as pathogenic markers, risk predictors, and therapeutic targets in ALD.

scholarly journals Case Report: Liraglutide for Weight Management in Beckwith-Wiedemann Syndromic Obesity

2021 ◽  
Vol 12 ◽  
Author(s):  
Marina Caputo ◽  
Tommaso Daffara ◽  
Simonetta Bellone ◽  
Valentina Mancioppi ◽  
Paolo Marzullo ◽  
...  
Keyword(s):  
Kinase Inhibitor ◽  
Sleep Apnea Syndrome ◽  
Genetic Obesity ◽  
Cyclin Dependent Kinase Inhibitor ◽  
Imprinting Disorder ◽  
Melanocortin 4 Receptor ◽  
First Case ◽  
Syndromic Obesity ◽  
Obstructive Sleep ◽  
Clinical Conditions

Genetic obesity, including syndromic and non-syndromic forms, represents a minority of cases compared to essential obesity but gene dysregulations lead to complex clinical conditions that make their management particularly difficult. Among them, Beckwith-Wiedemann syndrome (BWS) is a multisystem human genomic imprinting disorder characterized by overgrowth. We describe the first case of liraglutide treatment in an 18-year-old boy patient affected by BWS complicated by macroglossia, cryptorchidism, nephroblastoma, organomegaly, microscopic lymphocytic colitis, pharmacologically treated arterial hypertension, obesity, and obstructive sleep apnea syndrome. He presented a normal cognitive development. Body mass index at the time of first transition visit in the adult endocrinology department at the age of 18-years-old was 40.6 kg/m2 without glucose metabolism impairment. Lifestyle interventions failed because of poor compliance. During 20 months of 3.0 mg liraglutide treatment, a weight loss of 19 kg (−13.3%) and BMI reduction of 6.8 points were registered without side effects. To date, liraglutide treatment was effective on obesity in 7 subjects with Prader Willy Syndrome and 14 with melanocortin-4 receptor mutations. The efficacy of liraglutide in BWS could be related to a crosstalk among glucagon-like peptide (GLP)-1 system, mechanisms related to the cyclin-dependent kinase inhibitor 1C (CDKN1C), and dopamine mesolimbic circuit. Clinical trials aiming at a tailored medicine in genetic obesity are needed.

Genetic and Epigenetic Aspects of Obessity and Metabolic Syndrom in Child

2013 ◽  
Vol 4 (2) ◽  
pp. 3-11 ◽  
Author(s):  
Ludmila Viktorovna Tyrtova ◽  
Natalja Vladimirovna Parshina ◽  
Kristina Vladimirovna Skobeleva
Keyword(s):  
Physical Activity ◽  
Metabolic Syndrome ◽  
Early Childhood ◽  
Genetic Variants ◽  
Severe Obesity ◽  
Review Article ◽  
Epigenetic Factors ◽  
Early Prevention ◽  
The Individual

In a review article analyzes the role of heredity in the occurrence of obesity and metabolic syndrome. Debut of hyperphagia and severe obesity from early childhood are typical for monogenic forms and syndromes. Many nonspecific candidate-genes in combination form a polygenic basis for the accumulation of excess body fat, especially under the influence of irrational diet and low physical activity. Examined the role of epigenetic factors in the individual genetic variants in fetus, predisposing to obesity and metabolic syndrome after birth. Discuss the possibilities of early prevention of obesity and metabolic syndrome.

scholarly journals Impact of Genetic Variations and Epigenetic Mechanisms on the Risk of Obesity

2020 ◽  
Vol 21 (23) ◽  
pp. 9035
Author(s):  
Martina Chiurazzi ◽  
Mauro Cozzolino ◽  
Roberta Clara Orsini ◽  
Martina Di Maro ◽  
Matteo Nicola Dario Di Minno ◽  
...  
Keyword(s):  
Energy Balance ◽  
Early Onset ◽  
Severe Obesity ◽  
Metabolic Diseases ◽  
Current Knowledge ◽  
Epigenetic Mechanisms ◽  
Comprehensive Understanding ◽  
Genetic Obesity ◽  
Adequate Management

Rare genetic obesity disorders are characterized by mutations of genes strongly involved in the central or peripheral regulation of energy balance. These mutations are effective in causing the early onset of severe obesity and insatiable hunger (hyperphagia), suggesting that the genetic component can contribute to 40–70% of obesity. However, genes’ roles in the processes leading to obesity are still unclear. This review is aimed to summarize the current knowledge of the genetic causes of obesity, especially monogenic obesity, describing the role of epigenetic mechanisms in obesity and metabolic diseases. A comprehensive understanding of the underlying genetic and epigenetic mechanisms, with the metabolic processes they control, will permit adequate management and prevention of obesity.

Ovarian cancer and the evolution of subtype classifications using transcriptional profiling†

2019 ◽  
Vol 101 (3) ◽  
pp. 645-658 ◽  
Author(s):  
David P Cook ◽  
Barbara C Vanderhyden
Keyword(s):  
Ovarian Cancer ◽  
Molecular Mechanisms ◽  
Complex Disease ◽  
Transcriptional Profiling ◽  
Model Systems ◽  
Valuable Insight ◽  
Cancer Subtypes ◽  
Molecular Alterations ◽  
Spatially Resolved ◽  
Technological Advances

AbstractOvarian cancer is a complex disease with multiple subtypes, each having distinct histopathologies and variable responses to treatment. This review highlights the technological milestones and the studies that have applied them to change our definitions of ovarian cancer. Over the past 50 years, technologies such as microarrays and next-generation sequencing have led to the discovery of molecular alterations that define each of the ovarian cancer subtypes and has enabled further subclassification of the most common subtype, high-grade serous ovarian cancer (HGSOC). Improvements in mutational profiling have provided valuable insight, such as the ubiquity of TP53 mutations in HGSOC tumors. However, the information derived from these technological advances has also revealed the immense heterogeneity of this disease, from variation between patients to compositional differences within single masses. In looking forward, the emerging technologies for single-cell and spatially resolved transcriptomics will allow us to better understand the cellular composition and structure of tumors and how these contribute to the molecular subtypes. Attempts to incorporate the complexities ovarian cancer has resulted in increasing sophistication of model systems, and the increased precision in molecular profiling of ovarian cancers has already led to the introduction of inhibitors of poly (ADP-ribose) polymerases as a new class of treatments for ovarian cancer with DNA repair deficiencies. Future endeavors to define increasingly accurate classification strategies for ovarian cancer subtypes will allow for confident prediction of disease progression and provide important insight into potentially targetable molecular mechanisms specific to each subtype.

scholarly journals Epigenetic Regulation of microRNAs in Cancer: Shortening the Distance from Bench to Bedside

2021 ◽  
Vol 22 (14) ◽  
pp. 7350
Author(s):  
María J. Pajares ◽  
Ester Alemany-Cosme ◽  
Saioa Goñi ◽  
Eva Bandres ◽  
Cora Palanca-Ballester ◽  
...  
Keyword(s):  
Complex Disease ◽  
Epigenetic Factors ◽  
Clinical Value ◽  
Cellular Processes ◽  
Cancer Management ◽  
Promising Strategy ◽  
Epigenetic Machinery ◽  
Multiple Processes ◽  
Relevant Role ◽  
Non Coding Rnas

Cancer is a complex disease involving alterations of multiple processes, with both genetic and epigenetic features contributing as core factors to the disease. In recent years, it has become evident that non-coding RNAs (ncRNAs), an epigenetic factor, play a key role in the initiation and progression of cancer. MicroRNAs, the most studied non-coding RNAs subtype, are key controllers in a myriad of cellular processes, including proliferation, differentiation, and apoptosis. Furthermore, the expression of miRNAs is controlled, concomitantly, by other epigenetic factors, such as DNA methylation and histone modifications, resulting in aberrant patterns of expression upon the occurrence of cancer. In this sense, aberrant miRNA landscape evaluation has emerged as a promising strategy for cancer management. In this review, we have focused on the regulation (biogenesis, processing, and dysregulation) of miRNAs and their role as modulators of the epigenetic machinery. We have also highlighted their potential clinical value, such as validated diagnostic and prognostic biomarkers, and their relevant role as chromatin modifiers in cancer therapy.

scholarly journals Clinical management of patients with genetic obesity during COVID-19 pandemic: position paper of the ESE Growth & Genetic Obesity COVID-19 Study Group and Rare Endo-ERN main thematic group on Growth and Obesity

Endocrine ◽  
2021 ◽  
Author(s):  
Cornelis Jan De Groot ◽  
Christine Poitou Bernert ◽  
Muriel Coupaye ◽  
Karine Clement ◽  
Stavroula A. Paschou ◽  
...  
Keyword(s):  
Healthy Lifestyle ◽  
Position Paper ◽  
Study Group ◽  
Obesity Management ◽  
Genetic Obesity ◽  
Syndromic Obesity ◽  
Prevention And Treatment ◽  
Medication Dose ◽  
Inflammatory Phenotype ◽  
Intellectual Deficit

AbstractThis article aims to provide guidance on prevention and treatment of COVID-19 in patients with genetic obesity. Key principals of the management of patients with genetic obesity during COVID-19 pandemic for patients that have contracted COVID-19 are to be aware of: possible adrenal insufficiency (e.g., POMC deficiency, PWS); a more severe course in patients with concomitant immunodeficiency (e.g., LEP and LEPR deficiency), although defective leptin signalling could also be protective against the pro-inflammatory phenotype of COVID-19; disease severity being masked by insufficient awareness of symptoms in syndromic obesity patients with intellectual deficit (in particular PWS); to adjust medication dose to increased body size, preferably use dosing in m2; the high risk of malnutrition in patients with Sars-Cov2 infection, even in case of obesity. Key principals of the obesity management during the pandemic are to strive for optimal obesity management and a healthy lifestyle within the possibilities of the regulations to prevent weight (re)gain and to address anxiety within consultations, since prevalence of anxiety for COVID-19 is underestimated.

Risk Factors and Genetics in Wet-Form (Neovascular) Age-Related Macular Degeneration

2017 ◽  
pp. 167-172
Keyword(s):  
Risk Factors ◽  
Macular Degeneration ◽  
Complex Disease ◽  
Factor H ◽  
Age Related Macular Degeneration ◽  
Genetic Knowledge ◽  
Complement Factor ◽  
Epigenetic Factors ◽  
Age Related

Age-related macular degeneration (AMD) is a complex disease, with both genetic and environmental risk factors. Epigenetic factors also seem to play a role in the pathogenesis of AMD. Current genetic knowledge has brought opportunities for improved risk assessment and diagnosis of genetic variants. Complement factor H (CFH) and age-related maculopathy susceptibility 2 (ARMS2) are the most studied genes associated with AMD. A better understanding of the role of genetics in AMD may lead to personalized treatment in the future.

scholarly journals Anesthesia in Children with Neuroblastoma, Perioperative and Operative Management

Children ◽  
2021 ◽  
Vol 8 (5) ◽  
pp. 395
Author(s):  
Costanza Tognon ◽  
Rebecca Pulvirenti ◽  
Federica Fati ◽  
Federica De Corti ◽  
Elisabetta Viscardi ◽  
...  
Keyword(s):  
Multidisciplinary Care ◽  
Operative Management ◽  
Tumor Location ◽  
Biological Behavior ◽  
Cross Sectional ◽  
Pediatric Malignancy ◽  
Major Morbidity ◽  
Innovative Therapies ◽  
Patient Preparation

Neuroblastoma (NB) is the most common extracranial, solid, pediatric malignancy and, despite the constant progress of treatment and development of innovative therapies, remains a complex, challenging disease causing major morbidity and mortality in children. There is significant variability in the management of neuroblastoma, partially due to the heterogeneity of the clinical and biological behavior, and partially secondary to the different approaches between treating institutions. Anesthesia takes an integral part in the multidisciplinary care of patients with NB, from diagnosis to surgery and pain control. This paper aims to review and discuss the critical steps of the perioperative and operative management of children undergoing surgery for neuroblastoma. Anesthesia and analgesia largely depend on tumor location, surgical approach, and extension of the surgical dissection. Attention should be paid to the physio-pathological changes on cardiovascular, gastrointestinal, and immune systems induced by the tumor or by chemotherapy. At the time of surgery meticulous patient preparation needs to be carried out to optimize intraoperative monitoring and minimize the risk of complications. The cross-sectional role of anesthesia in cancer care requires effective communication between all members of the multidisciplinary team.

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