-
Advances in Nutrition (Bethesda, Md.) Jan 2019The global obesity epidemic continues its relentless advance, currently affecting >2 billion people. This paper explores alternative ways to assess the potential disease...
The global obesity epidemic continues its relentless advance, currently affecting >2 billion people. This paper explores alternative ways to assess the potential disease impact of the epidemic, which is currently based almost exclusively on body mass index (BMI) data. It also argues in favor of concerted efforts to modify the built ecosystem that is driving the obesity epidemic. Most of the epidemiologic data on obesity are based on BMI (in kg/m2) and use the ranges of 18.5-24.9 for normality, 25-29.9 for overweight, and ≥30 for obesity. But the gap between the median of the "normal" BMI distribution (∼22) and the current population BMI of, for example, the United States (27.7) has become so wide that it is unlikely that we will be able to close that gap in the near future. Furthermore, the correlation between BMI and disease risk is not linear. Over 60% of the global disease burden of obesity affects individuals with a BMI ≥30, who comprise only ∼10% of the global population of overweight/obese persons. Furthermore, BMI accounts for only ∼17% of the risk of insulin resistance and subsequent type 2 diabetes in the BMI ≥25 population. Epigenetics, specifically DNA methylation, appears to play a far more important role than BMI in determining the risk of obesity's comorbidities, such as diabetes. Similarly, socioeconomic status carries a higher risk than BMI level for the development of obesity-related noncommunicable diseases. Finally, the built environment that sustains our species' lifestyle is a major driver of the obesity epidemic. Modifying that ecosystem will require no less than a social movement, one able to promote and sustain the necessary coordinated action of virtually all sectors of society.
Topics: Body Mass Index; Comorbidity; Cost of Illness; DNA Methylation; Diabetes Mellitus, Type 2; Ecosystem; Environment Design; Epigenesis, Genetic; Global Health; Humans; Insulin Resistance; Life Style; Obesity; Social Class
PubMed: 30721956
DOI: 10.1093/advances/nmy055 -
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 -
BMJ (Clinical Research Ed.) Feb 2017Obesity is the most common medical condition in women of reproductive age. Obesity during pregnancy has short term and long term adverse consequences for both mother and... (Review)
Review
Obesity is the most common medical condition in women of reproductive age. Obesity during pregnancy has short term and long term adverse consequences for both mother and child. Obesity causes problems with infertility, and in early gestation it causes spontaneous pregnancy loss and congenital anomalies. Metabolically, obese women have increased insulin resistance in early pregnancy, which becomes manifest clinically in late gestation as glucose intolerance and fetal overgrowth. At term, the risk of cesarean delivery and wound complications is increased. Postpartum, obese women have an increased risk of venous thromboembolism, depression, and difficulty with breast feeding. Because 50-60% of overweight or obese women gain more than recommended by Institute of Medicine gestational weight guidelines, postpartum weight retention increases future cardiometabolic risks and prepregnancy obesity in subsequent pregnancies. Neonates of obese women have increased body fat at birth, which increases the risk of childhood obesity. Although there is no unifying mechanism responsible for the adverse perinatal outcomes associated with maternal obesity, on the basis of the available data, increased prepregnancy maternal insulin resistance and accompanying hyperinsulinemia, inflammation, and oxidative stress seem to contribute to early placental and fetal dysfunction. We will review the pathophysiology underlying these data and try to shed light on the specific underlying mechanisms.
Topics: Disease Management; Female; Humans; Infant, Newborn; Obesity; Pregnancy; Pregnancy Complications; Pregnancy Outcome; Time
PubMed: 28179267
DOI: 10.1136/bmj.j1 -
Fertility and Sterility Apr 2017The worldwide upward trend in obesity has been dramatic, now affecting more than 20% of American women of reproductive age. Obesity is associated with many adverse... (Review)
Review
The worldwide upward trend in obesity has been dramatic, now affecting more than 20% of American women of reproductive age. Obesity is associated with many adverse maternal and fetal effects prenatally, but it also exerts a negative influence on female fertility. Obese women are more likely to have ovulatory dysfunction due to dysregulation of the hypothalamic-pituitary-ovarian axis. Women with polycystic ovarian syndrome who are also obese demonstrate a more severe metabolic and reproductive phenotype. Obese women have reduced fecundity even when eumenorrheic and demonstrate poorer outcomes with the use of in vitro fertilization. Obesity appears to affect the oocyte and the preimplantation embryo, with disrupted meiotic spindle formation and mitochondrial dynamics. Excess free fatty acids may have a toxic effect in reproductive tissues, leading to cellular damage and a chronic low-grade inflammatory state. Altered levels of adipokines, such as leptin, in the obese state can affect steroidogenesis and directly affect the developing embryo. The endometrium is also susceptible, with evidence of impaired stromal decidualization in obese women. This may explain subfecundity due to impaired receptivity, and may lead to placental abnormalities as manifested by higher rates of miscarriage, stillbirth, and preeclampsia in the obese population. Many interventions have been explored to mitigate the effect of obesity on infertility, including weight loss, physical activity, dietary factors, and bariatric surgery. These data are largely mixed, with few high quality studies to guide us. As we improve our understanding of the pathophysiology of obesity in human reproduction we hope to identify novel treatment strategies.
Topics: Adipose Tissue; Adiposity; Bariatric Surgery; Diet; Female; Fertility; Genetic Predisposition to Disease; Healthy Lifestyle; Humans; Hypothalamo-Hypophyseal System; Infertility, Female; Lipid Metabolism; Obesity; Oocytes; Ovary; Pregnancy; Pregnancy Complications; Risk Assessment; Risk Factors; Risk Reduction Behavior; Sedentary Behavior; Weight Loss
PubMed: 28292619
DOI: 10.1016/j.fertnstert.2017.01.017 -
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 -
The Journal of Allergy and Clinical... Apr 2018Obesity is a vast public health problem and both a major risk factor and disease modifier for asthma in children and adults. Obese subjects have increased asthma risk,... (Review)
Review
Obesity is a vast public health problem and both a major risk factor and disease modifier for asthma in children and adults. Obese subjects have increased asthma risk, and obese asthmatic patients have more symptoms, more frequent and severe exacerbations, reduced response to several asthma medications, and decreased quality of life. Obese asthma is a complex syndrome, including different phenotypes of disease that are just beginning to be understood. We examine the epidemiology and characteristics of this syndrome in children and adults, as well as the changes in lung function seen in each age group. We then discuss the better recognized factors and mechanisms involved in disease pathogenesis, focusing particularly on diet and nutrients, the microbiome, inflammatory and metabolic dysregulation, and the genetics/genomics of obese asthma. Finally, we describe current evidence on the effect of weight loss and mention some important future directions for research in the field.
Topics: Adult; Asthma; Child; Humans; Microbiota; Obesity; Quality of Life; Syndrome
PubMed: 29627041
DOI: 10.1016/j.jaci.2018.02.004 -
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 -
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 -
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 -
Acta Bio-medica : Atenei Parmensis Aug 2022Obesity has been associated with reduced fertility, although the dynamics and mechanisms which link excess weight to reduced fertility are not yet fully clarified. Obese...
Obesity has been associated with reduced fertility, although the dynamics and mechanisms which link excess weight to reduced fertility are not yet fully clarified. Obese women, especially those with central obesity, are less likely to conceive per cycle. Obese women suffer from perturbations of the hypothalamus-pituitary-ovary axis, disturbances of the menstrual cycle and are up to three times more likely to suffer from oligo/anovulation. A delicate hormonal balance regulates follicular development and the maturation of oocytes and it has been observed that obesity can alter the hormonal environment: adipocytes, in fact, are responsible for the production of a hormone called leptin (present in high quantities in obese women) which has been associated with reduced fecundity. In addition to compromising ovulation, obesity negatively affects the development and implantation of the endometrium. The expression of polycystic ovary syndrome (PCOS) is regulated, in part, by weight, so obese women with PCOS often have a more severe phenotype and higher subfertility rates. Furthermore, obesity impairs women's response to medically assisted procreation (MAP) treatments. The authors have set out to delineate a broad-ranging overview of obesity's impact on female fertility, by drawing upon sources spanning the 1994-2022 period. Assisted reproductive technology (ART) procedures are also discussed as they relate to obese patients. In addition the dynamics by which maternal obesity reportedly affects fetal, neonatal and child development have also been briefly enunciated.
Topics: Anovulation; Female; Fertility; Humans; Infertility, Female; Obesity; Polycystic Ovary Syndrome; Pregnancy
PubMed: 36043953
DOI: 10.23750/abm.v93i4.13466