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Lancet (London, England) Apr 2023The goal of obesity management is to improve health. Sustained weight loss of more than 10% overall bodyweight improves many of the complications associated with obesity... (Review)
Review
The goal of obesity management is to improve health. Sustained weight loss of more than 10% overall bodyweight improves many of the complications associated with obesity (eg, prevention and control of type 2 diabetes, hypertension, fatty liver disease, and obstructive sleep apnoea), as well as quality of life. Maintenance of weight loss is the major challenge of obesity management. Like all chronic diseases, managing obesity requires a long-term, multimodal approach, taking into account each individual's treatment goals, and the benefit and risk of different therapies. In conjunction with lifestyle interventions, anti-obesity medications and bariatric surgery improve the maintenance of weight loss and associated health gains. Most available anti-obesity medications act on central appetite pathways to reduce hunger and food reward. In the past 5 years, therapeutic advances have seen the development of targeted treatments for monogenic obesities and a new generation of anti-obesity medications. These highly effective anti-obesity medications are associated with weight losses of more than 10% of overall bodyweight in more than two-thirds of clinical trial participants. Long-term data on safety, efficacy, and cardiovascular outcomes are awaited. Long-term studies have shown that bariatric surgical procedures typically lead to a durable weight loss of 25% and rapid, sustained improvements in complications of obesity, although they have not yet been compared with new-generation highly effective anti-obesity medications. Further work is required to determine optimal patient-specific treatment strategies, including combinations of lifestyle interventions, anti-obesity medications, endoscopic and bariatric surgical procedures, and to ensure equitable access to effective treatments.
Topics: Adult; Humans; Diabetes Mellitus, Type 2; Quality of Life; Obesity; Bariatric Surgery; Anti-Obesity Agents; Body Weight; Weight Loss
PubMed: 36774932
DOI: 10.1016/S0140-6736(22)02403-5 -
Circulation Research May 2020This review addresses the interplay between obesity, type 2 diabetes mellitus, and cardiovascular diseases. It is proposed that obesity, generally defined by an excess... (Review)
Review
This review addresses the interplay between obesity, type 2 diabetes mellitus, and cardiovascular diseases. It is proposed that obesity, generally defined by an excess of body fat causing prejudice to health, can no longer be evaluated solely by the body mass index (expressed in kg/m) because it represents a heterogeneous entity. For instance, several cardiometabolic imaging studies have shown that some individuals who have a normal weight or who are overweight are at high risk if they have an excess of visceral adipose tissue-a condition often accompanied by accumulation of fat in normally lean tissues (ectopic fat deposition in liver, heart, skeletal muscle, etc). On the other hand, individuals who are overweight or obese can nevertheless be at much lower risk than expected when faced with excess energy intake if they have the ability to expand their subcutaneous adipose tissue mass, particularly in the gluteal-femoral area. Hence, excessive amounts of visceral adipose tissue and of ectopic fat largely define the cardiovascular disease risk of overweight and moderate obesity. There is also a rapidly expanding subgroup of patients characterized by a high accumulation of body fat (severe obesity). Severe obesity is characterized by specific additional cardiovascular health issues that should receive attention. Because of the difficulties of normalizing body fat content in patients with severe obesity, more aggressive treatments have been studied in this subgroup of individuals such as obesity surgery, also referred to as metabolic surgery. On the basis of the above, we propose that we should refer to obesities rather than obesity.
Topics: Animals; Cardiovascular Diseases; Diabetes Mellitus; Humans; Obesity
PubMed: 32437302
DOI: 10.1161/CIRCRESAHA.120.316101 -
The Indian Journal of Medical Research Jan 2020Obesity is a serious medical condition worldwide, which needs new approaches and recognized international consensus in treating diseases leading to morbidity. The aim of... (Review)
Review
Obesity is a serious medical condition worldwide, which needs new approaches and recognized international consensus in treating diseases leading to morbidity. The aim of this review was to examine heterogeneous links among the various phenotypes of obesity in adults. Proteins and associated genes in each group were analysed to differentiate between biomarkers. A variety of terms for classification and characterization within this pathology are currently in use; however, there is no clear consensus in terminology. The most significant groups reviewed include metabolically healthy obese, metabolically abnormal obese, metabolically abnormal, normal weight and sarcopenic obese. These phenotypes do not define particular genotypes or epigenetic gene regulation, or proteins related to inflammation. There are many other genes linked to obesity, though the value of screening all of those for diagnosis has low predictive results, as there are no significant biomarkers. It is important to establish a consensus in the terminology used and the characteristics attributed to obesity subtypes. The identification of specific molecular biomarkers is also required for better diagnosis in subtypes of obesity.
Topics: Adult; Biomarkers; Genotype; Humans; Obesity; Phenotype; Proteins
PubMed: 32134010
DOI: 10.4103/ijmr.IJMR_1768_17 -
European Journal of Haematology Mar 2021The prevalence of obesity is increasing and progressively influencing physician-patient interactions. While there is a sizable amount of data demonstrating that obesity... (Review)
Review
The prevalence of obesity is increasing and progressively influencing physician-patient interactions. While there is a sizable amount of data demonstrating that obesity is a state of low-grade inflammation, to our knowledge, there is no single review summarizing its effects on hematologic parameters and thrombotic risk. We performed a literature search which largely surfaced observational studies, with a few systematic reviews and meta-analyses of these studies. We took care to review the mechanisms driving an inflammatory state and obesity's effect on white blood cells, red blood cells, platelets, and thrombotic risk. There is an observed relative, and sometimes absolute leukocytosis driven by this inflammatory state. Obesity is also associated with increased platelet counts and an increased risk for venous thromboembolism (VTE). Lastly, the association between obesity, iron deficiency (ID), and red blood cell counts may be present but remains uncertain. Recognizing the above associations may provide clinicians with reassurance regarding otherwise unexplained hematologic abnormalities in obese individuals. We hope this review will prompt future studies to further understand the underlying mechanisms driving these abnormalities and identify modifiable risk factors and potential therapeutic targets to prevent the development of probable obesity-associated conditions with significant morbidity and mortality, such as ID and VTE.
Topics: Adipose Tissue; Animals; Biomarkers; Cytokines; Disease Susceptibility; Humans; Inflammation; Inflammation Mediators; Leukocyte Count; Leukocytosis; Obesity; Sex Factors
PubMed: 33270290
DOI: 10.1111/ejh.13560 -
Biomedicine & Pharmacotherapy =... May 2021Currently, obesity has become a global health issue and is referred to as an epidemic. Dysfunctional obese adipose tissue plays a pivotal role in the development of... (Review)
Review
Currently, obesity has become a global health issue and is referred to as an epidemic. Dysfunctional obese adipose tissue plays a pivotal role in the development of insulin resistance. However, the mechanism of how dysfunctional obese-adipose tissue develops insulin-resistant circumstances remains poorly understood. Therefore, this review attempts to highlight the potential mechanisms behind obesity-associated insulin resistance. Multiple risk factors are directly or indirectly associated with the increased risk of obesity; among them, environmental factors, genetics, aging, gut microbiota, and diets are prominent. Once an individual becomes obese, adipocytes increase in their size; therefore, adipose tissues become larger and dysfunctional, recruit macrophages, and then these polarize to pro-inflammatory states. Enlarged adipose tissues release excess free fatty acids (FFAs), reactive oxygen species (ROS), and pro-inflammatory cytokines. Excess systemic FFAs and dietary lipids enter inside the cells of non-adipose organs such as the liver, muscle, and pancreas, and are deposited as ectopic fat, generating lipotoxicity. Toxic lipids dysregulate cellular organelles, e.g., mitochondria, endoplasmic reticulum, and lysosomes. Dysregulated organelles release excess ROS and pro-inflammation, resulting in systemic inflammation. Long term low-grade systemic inflammation prevents insulin from its action in the insulin signaling pathway, disrupts glucose homeostasis, and results in systemic dysregulation. Overall, long-term obesity and overnutrition develop into insulin resistance and chronic low-grade systemic inflammation through lipotoxicity, creating the circumstances to develop clinical conditions. This review also shows that the liver is the most sensitive organ undergoing insulin impairment faster than other organs, and thus, hepatic insulin resistance is the primary event that leads to the subsequent development of peripheral tissue insulin resistance.
Topics: Adipose Tissue; Animals; Humans; Insulin Resistance; Obesity
PubMed: 33561645
DOI: 10.1016/j.biopha.2021.111315 -
Gastroenterology Jan 2021Changes in the intestinal microbiome have been associated with obesity and type 2 diabetes, in epidemiological studies and studies of the effects of fecal transfer in... (Review)
Review
Metabolism and Metabolic Disorders and the Microbiome: The Intestinal Microbiota Associated With Obesity, Lipid Metabolism, and Metabolic Health-Pathophysiology and Therapeutic Strategies.
Changes in the intestinal microbiome have been associated with obesity and type 2 diabetes, in epidemiological studies and studies of the effects of fecal transfer in germ-free mice. We review the mechanisms by which alterations in the intestinal microbiome contribute to development of metabolic diseases, and recent advances, such as the effects of the microbiome on lipid metabolism. Strategies have been developed to modify the intestinal microbiome and reverse metabolic alterations, which might be used as therapies. We discuss approaches that have shown effects in mouse models of obesity and metabolic disorders, and how these might be translated to humans to improve metabolic health.
Topics: Animals; Diabetes Mellitus, Type 2; Disease Models, Animal; Gastrointestinal Microbiome; Humans; Insulin Resistance; Lipid Metabolism; Metabolic Diseases; Mice; Obesity
PubMed: 33253685
DOI: 10.1053/j.gastro.2020.10.057 -
Drugs Feb 2021Setmelanotide (IMCIVREE™, Rhythm Pharmaceuticals) is a melanocortin-4 (MC4) receptor agonist developed for the treatment of obesity arising from proopiomelanocortin... (Review)
Review
Setmelanotide (IMCIVREE™, Rhythm Pharmaceuticals) is a melanocortin-4 (MC4) receptor agonist developed for the treatment of obesity arising from proopiomelanocortin (POMC), proprotein convertase subtilisin/kexin type 1 (PCSK1), or leptin receptor (LEPR) deficiency. The drug has received its first approval in the USA for chronic weight management in patients 6 years and older with obesity caused by POMC, PCSK1 and LEPR deficiency and has been granted PRIority MEdicines (PRIME) designation by the European Medicines Agency for the treatment of obesity and the control of hunger associated with deficiency disorders of the MC4 receptor pathway. Setmelanotide is also being developed in other rare genetic disorders associated with obesity including Bardet-Biedl Syndrome, Alström Syndrome, POMC and other MC4R pathway heterozygous deficiency obesities, and POMC epigenetic disorders. This article summarizes the milestones in the development of setmelanotide leading to this first approval for obesity caused by POMC, PCSK1 and LEPR deficiency.
Topics: Humans; Molecular Conformation; Obesity; Receptor, Melanocortin, Type 4; alpha-MSH
PubMed: 33638809
DOI: 10.1007/s40265-021-01470-9 -
Journal of Clinical Research in... May 2023Obesity derives from impaired central control of body weight, implying interaction between environment and an individual genetic predisposition. Genetic obesities,... (Review)
Review
Obesity derives from impaired central control of body weight, implying interaction between environment and an individual genetic predisposition. Genetic obesities, including monogenic and syndromic obesities, are rare and complex neuro-endocrine pathologies where the genetic contribution is predominant. Severe and early-onset obesity with eating disorders associated with frequent comorbidities make these diseases challenging. Their current estimated prevalence of 5-10% in severely obese children is probably underestimated due to the limited access to genetic diagnosis. A central alteration of hypothalamic regulation of weight implies that the leptin-melanocortin pathway is responsible for the symptoms. The management of genetic obesity has so far been only based, above all, on lifestyle intervention, especially regarding nutrition and physical activity. New therapeutic options have emerged in the last years for these patients, raising great hope to manage their complex situation and improve quality of life. Implementation of genetic diagnosis in clinical practice is thus of paramount importance to allow individualized care. This review describes the current clinical management of genetic obesity and the evidence on which it is based. Some insights will also be provided into new therapies under evaluation.
Topics: Pediatric Obesity; Humans; Child; Genetic Predisposition to Disease; Male; Female; Quality of Life; Bariatric Surgery; Exercise; Diet, Healthy; Anti-Obesity Agents
PubMed: 37191347
DOI: 10.4274/jcrpe.galenos.2023.2023-3-2 -
International Journal of Molecular... Dec 2021There is a large literature on the relationship between obesity and bone. What we can conclude from this review is that the increase in body weight causes an increase in... (Review)
Review
There is a large literature on the relationship between obesity and bone. What we can conclude from this review is that the increase in body weight causes an increase in BMD, both for a mechanical effect and for the greater amount of estrogens present in the adipose tissue. Nevertheless, despite an apparent strengthening of the bone witnessed by the increased BMD, the risk of fracture is higher. The greater risk of fracture in the obese subject is due to various factors, which are carefully analyzed by the Authors. These factors can be divided into metabolic factors and increased risk of falls. Fractures have an atypical distribution in the obese, with a lower incidence of typical osteoporotic fractures, such as those of hip, spine and wrist, and an increase in fractures of the ankle, upper leg, and humerus. In children, the distribution is different, but it is not the same in obese and normal-weight children. Specifically, the fractures of the lower limb are much more frequent in obese children. Sarcopenic obesity plays an important role. The authors also review the available literature regarding the effects of high-fat diet, weight loss and bariatric surgery.
Topics: Body Mass Index; Body Weight; Fractures, Bone; Humans; Obesity; Risk Factors
PubMed: 34948466
DOI: 10.3390/ijms222413662 -
International Journal of Molecular... Apr 2020Obesity has become a global epidemic and a public health crisis in the Western World, experiencing a threefold increase in prevalence since 1975. High-caloric diets and... (Review)
Review
Obesity has become a global epidemic and a public health crisis in the Western World, experiencing a threefold increase in prevalence since 1975. High-caloric diets and sedentary lifestyles have been identified as significant contributors to this widespread issue, although the role of genetic, social, and environmental factors in obesity's pathogenesis remain incompletely understood. In recent years, much attention has been drawn to the contribution of the gut microbiota in the development of obesity. Indeed, research has shown that in contrast to their healthier counterparts the microbiomes of obese individuals are structurally and functionally distinct, strongly suggesting microbiome as a potential target for obesity therapeutics. In particular, pre and probiotics have emerged as effective and integrative means of modulating the microbiome, in order to reverse the microbial dysbiosis associated with an obese phenotype. The following review brings forth animal and human research supporting the myriad of mechanisms by which the microbiome affects obesity, as well as the strengths and limitations of probiotic or prebiotic supplementation for the prevention and treatment of obesity. Finally, we set forth a roadmap for the comprehensive development of functional food solutions in combatting obesity, to capitalize on the potential of pre/probiotic therapies in optimizing host health.
Topics: Animals; Bile Acids and Salts; Diet; Disease Susceptibility; Dysbiosis; Energy Metabolism; Functional Food; Gastrointestinal Microbiome; Humans; Metabolic Syndrome; Microbiota; Obesity; Prebiotics; Probiotics
PubMed: 32326175
DOI: 10.3390/ijms21082890