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Maedica Sep 2022Obesity is defined by an imbalance between energy expenditure and energy consumption. Presently, it is considered a global problem because people are consuming junk food...
Obesity is defined by an imbalance between energy expenditure and energy consumption. Presently, it is considered a global problem because people are consuming junk food and doing less physical activity in every country of the world. It is all due to sedentary life style. The currently available drugs for the treatment of obesity are not giving satisfactory results as they have many adverse effects along with rebound obesity complications. To evaluate new drug in pre-clinical study, we need to have better supportive animal models. Obesity can be induced by giving drugs, fat food, surgical procedures, and by genetic modifications. In the present review, various obesity induced models have been explained to evaluate new compounds. In experimental animal models, monogenic and polygenic obesity models have been reviewed, with a proper pathway to prepare new drugs being given. While in the existing models, genetic obesity models were not explained so far, here genetic engineered transgenic models were described to evaluate new anti-obesity drugs. This short review on chemically and surgically induced obesity models aimed to provide a better understanding of the experimental design of obesity.
PubMed: 36540593
DOI: 10.26574/maedica.2022.17.3.706 -
Revista Do Colegio Brasileiro de... Oct 2018Knowledge about animal models for metabolic study is the basis of research in this area. This work aims to review the main animal models used in the study of obesity and... (Review)
Review
Knowledge about animal models for metabolic study is the basis of research in this area. This work aims to review the main animal models used in the study of obesity and metabolic syndrome. For this, we performed a search in the Pubmed database using the terms "animal models", "obesity", "metabolic syndrome" and "bariatric surgery". Several species of animals can be used for the study of metabolic disorders. However, rodents are the most commonly used, both as monogenic models and as diet-induced obesity (DIO) ones. Monogenic animals are the best choice if only one aspect is being evaluated. DIO animals tend to better demonstrate the interaction between disease, environment and genetics. However, they are still not fully effective in providing understanding of all disease mechanisms.
Topics: Animals; Bariatric Surgery; Cats; Disease Models, Animal; Dogs; Haplorhini; Metabolic Syndrome; Mice; Obesity; Rats
PubMed: 30379216
DOI: 10.1590/0100-6991e-20181975 -
Public Health Nutrition Oct 2007The aim was to review and update advances in genetics of obesity. (Review)
Review
OBJECTIVE
The aim was to review and update advances in genetics of obesity.
DESIGN
Analysis and interpretation of recent investigations about regulating the energy balance as well as about gene-nutrient interactions and current nutri-genomic research methods. BACKGROUND AND MAIN STATEMENTS: Obesity results from a long-term positive energy balance. However, its rising prevalence in developed and developing societies must reflect lifestyle changes, since genetic susceptibility remains stable over many generations. Like most complex diseases, obesity derives from a failure of adequate homoeostasis within the physiological system controlling body weight. The identification of genes that are involved in syndromic, monogenic and polygenic obesity has seriously improved our knowledge of body weight regulation. This disorder may arise from a deregulation at the genetic level (e.g. gene transcription or altered protein function) or environmental exposure (e.g. diet, physical activity, etc.).
CONCLUSIONS
In practice, obesity involves the interaction between genetic and environmental factors.
Topics: Adipogenesis; Diet; Energy Metabolism; Genetic Predisposition to Disease; Homeostasis; Humans; Life Style; Nutrigenomics; Obesity; Prevalence
PubMed: 17903322
DOI: 10.1017/S1368980007000626 -
Progress in Molecular Biology and... 2016PCSK1, encoding prohormone convertase 1/3 (PC1/3), was one of the first genes linked to monogenic early-onset obesity. PC1/3 is a protease involved in the biosynthetic... (Review)
Review
PCSK1, encoding prohormone convertase 1/3 (PC1/3), was one of the first genes linked to monogenic early-onset obesity. PC1/3 is a protease involved in the biosynthetic processing of a variety of neuropeptides and prohormones in endocrine tissues. PC1/3 activity is essential for the activating cleavage of many peptide hormone precursors implicated in the regulation of food ingestion, glucose homeostasis, and energy homeostasis, for example, proopiomelanocortin, proinsulin, proglucagon, and proghrelin. A large number of genome-wide association studies in a variety of different populations have now firmly established a link between three PCSK1 polymorphisms frequent in the population and increased risk of obesity. Human subjects with PC1/3 deficiency, a rare autosomal-recessive disorder caused by the presence of loss-of-function mutations in both alleles, are obese and display a complex set of endocrinopathies. Increasing numbers of genetic diagnoses of infants with persistent diarrhea has recently led to the finding of many novel PCSK1 mutations. PCSK1-deficient infants experience severe intestinal malabsorption during the first years of life, requiring controlled nutrition; these children then become hyperphagic, with associated obesity. The biochemical characterization of novel loss-of-function PCSK1 mutations has resulted in the discovery of new pathological mechanisms affecting the cell biology of the endocrine cell beyond simple loss of enzyme activity, for example, dominant-negative effects of certain mutants on wild-type PC1/3 protein, and activation of the cellular unfolded protein response by endoplasmic reticulum-retained mutants. A better understanding of these molecular and cellular pathologies may illuminate possible treatments for the complex endocrinopathy of PCSK1 deficiency, including obesity.
Topics: Humans; Obesity; Polymorphism, Single Nucleotide; Proprotein Convertase 1
PubMed: 27288825
DOI: 10.1016/bs.pmbts.2015.12.001 -
Cells Apr 2022Obesity, one of the major problems in modern human society, is correlated with various diseases, including type 2 diabetes mellitus (T2DM). In particular,... (Review)
Review
Obesity, one of the major problems in modern human society, is correlated with various diseases, including type 2 diabetes mellitus (T2DM). In particular, epidemiological and experimental evidence indicates that obesity is closely linked to at least 13 different types of cancer. The mechanisms that potentially explain the link between obesity and cancer include hyperactivation of the IGF pathway, metabolic dysregulation, dysfunctional angiogenesis, chronic inflammation, and interaction between pro-inflammatory cytokines, endocrine hormones, and adipokines. However, how the largely uniform morbidity of obesity leads to different types of cancer still needs to be investigated. To study the link between obesity and cancer, researchers have commonly used preclinical animal models, particularly mouse models. These models include monogenic models of obesity (e.g., and mice) and genetically modified mouse models of human cancers (e.g., -driven pancreatic cancer, -mutated colorectal cancer, and Her2/neu-overexpressing breast cancer). The experimental results obtained using these mouse models revealed strong evidence of a link between obesity and cancer and suggested their underlying mechanisms.
Topics: Adipokines; Animals; Breast Neoplasms; Diabetes Mellitus, Type 2; Disease Models, Animal; Female; Humans; Mice; Obesity
PubMed: 35563777
DOI: 10.3390/cells11091472 -
Molecules and Cells Apr 2022A primary cilium, a hair-like protrusion of the plasma membrane, is a pivotal organelle for sensing external environmental signals and transducing intracellular... (Review)
Review
A primary cilium, a hair-like protrusion of the plasma membrane, is a pivotal organelle for sensing external environmental signals and transducing intracellular signaling. An interesting linkage between cilia and obesity has been revealed by studies of the human genetic ciliopathies Bardet-Biedl syndrome and Alström syndrome, in which obesity is a principal manifestation. Mouse models of cell type-specific cilia dysgenesis have subsequently demonstrated that ciliary defects restricted to specific hypothalamic neurons are sufficient to induce obesity and hyperphagia. A potential mechanism underlying hypothalamic neuron cilia-related obesity is impaired ciliary localization of G protein-coupled receptors involved in the regulation of appetite and energy metabolism. A well-studied example of this is melanocortin 4 receptor (MC4R), mutations in which are the most common cause of human monogenic obesity. In the paraventricular hypothalamus neurons, a blockade of ciliary trafficking of MC4R as well as its downstream ciliary signaling leads to hyperphagia and weight gain. Another potential mechanism is reduced leptin signaling in hypothalamic neurons with defective cilia. Leptin receptors traffic to the periciliary area upon leptin stimulation. Moreover, defects in cilia formation hamper leptin signaling and actions in both developing and differentiated hypothalamic neurons. The list of obesity-linked ciliary proteins is expending and this supports a tight association between cilia and obesity. This article provides a brief review on the mechanism of how ciliary defects in hypothalamic neurons facilitate obesity.
Topics: Animals; Cilia; Humans; Hyperphagia; Hypothalamus; Leptin; Mice; Obesity
PubMed: 35387896
DOI: 10.14348/molcells.2022.2046 -
Children (Basel, Switzerland) Jan 2024Obesity is a significant health problem with a continuously increasing prevalence among children and adolescents that has become a modern pandemic during the last... (Review)
Review
Obesity is a significant health problem with a continuously increasing prevalence among children and adolescents that has become a modern pandemic during the last decades. Nowadays, the genetic contribution to obesity is well-established. For this narrative review article, we searched PubMed and Scopus databases for peer-reviewed research, review articles, and meta-analyses regarding the genetics of obesity and current pharmacological treatment, published in the English language with no time restrictions. We also screened the references of the selected articles for possible additional articles in order to include most of the key recent evidence. Our research was conducted between December 2022 and December 2023. We used the terms "obesity", "genetics", "monogenic", "syndromic", "drugs", "autosomal dominant", "autosomal recessive", "leptin-melanocortin pathway", and "children" in different combinations. Recognizing the genetic background in obesity can enhance the effectiveness of treatment. During the last years, intense research in the field of obesity treatment has increased the number of available drugs. This review analyzes the main categories of syndromic and monogenic obesity discussing current data on genetic-based pharmacological treatment of genetic obesity and highlighting the necessity that cases of genetic obesity should follow specific, pharmacological treatment based on their genetic background.
PubMed: 38397265
DOI: 10.3390/children11020153 -
Journal of Obesity & Metabolic Syndrome Dec 2021Childhood obesity has been increasing steadily in recent decades, and severe childhood obesity has emerged as a major public health problem both nationally and... (Review)
Review
Childhood obesity has been increasing steadily in recent decades, and severe childhood obesity has emerged as a major public health problem both nationally and internationally. A current concern is that lockdown due to the coronavirus disease 2019 (COVID-19) pandemic could exacerbate the spread of childhood obesity and increase the gap in obesity risk. Recent research results indicate the aggravation of obesity after school closures. The consequences of severe childhood obesity are more devastating than those of mild to moderate obesity. Children with severe obesity are at greater risk than others for hypertension, type 2 diabetes, metabolic syndrome, non-alcoholic fatty liver disease, atherosclerosis, and adult obesity. Accurately assessing and diagnosing a child with severe obesity is the key to implementing successful therapy. A detailed and accurate patient history and physical examination are important to discriminate monogenic obesity and metabolic syndrome diagnoses from severe obesity without an underlying cause. Psychosocial factors, including eating behaviors, should be assessed to facilitate better weight management outcomes. Treatment options for severe pediatric obesity include lifestyle modification therapy, pharmacotherapy, and metabolic and bariatric surgery. However, lifestyle modification should be the priority. Although progress has been made, safe and effective treatment for severe pediatric obesity is still challenging. More efforts and innovations are needed to find a solution for the huge medical and emotional burden that these children and their families carry. Public health organizations also need to make efforts to encourage and normalize healthy eating habits and exercise to prevent severe obesity in childhood.
PubMed: 34924365
DOI: 10.7570/jomes21063 -
PeerJ 2015Obesity is a major public health concern. This condition results from a constant and complex interplay between predisposing genes and environmental stimuli. Current... (Review)
Review
Obesity is a major public health concern. This condition results from a constant and complex interplay between predisposing genes and environmental stimuli. Current attempts to manage obesity have been moderately effective and a better understanding of the etiology of obesity is required for the development of more successful and personalized prevention and treatment options. To that effect, mouse models have been an essential tool in expanding our understanding of obesity, due to the availability of their complete genome sequence, genetically identified and defined strains, various tools for genetic manipulation and the accessibility of target tissues for obesity that are not easily attainable from humans. Our knowledge of monogenic obesity in humans greatly benefited from the mouse obesity genetics field. Genes underlying highly penetrant forms of monogenic obesity are part of the leptin-melanocortin pathway in the hypothalamus. Recently, hypothesis-generating genome-wide association studies for polygenic obesity traits in humans have led to the identification of 119 common gene variants with modest effect, most of them having an unknown function. These discoveries have led to novel animal models and have illuminated new biologic pathways. Integrated mouse-human genetic approaches have firmly established new obesity candidate genes. Innovative strategies recently developed by scientists are described in this review to accelerate the identification of causal genes and deepen our understanding of obesity etiology. An exhaustive dissection of the molecular roots of obesity may ultimately help to tackle the growing obesity epidemic worldwide.
PubMed: 25825681
DOI: 10.7717/peerj.856