Obesity pharmacotherapy - update 2023.

The increasing prevalence of obesity and its associated complications leads to the need to intensify its prevention and treatment. The treatment of obesity is currently based on lifestyle modification, which often fails in the long term. For the next decade, the long-term administration of anti-obesity drugs, i.e. drugs that have a positive effect not only on the reduction of excess weight but also on the health risks associated with obesity, seems to be a necessary part of obesity treatment, along with surgical approaches. This text provides an overview of the current options for the pharmacotherapy of obesity, including their indications, appropriate patient selection and adverse effects of treatment. It also provides an overview of studies that demonstrate the long-term efficacy and safety of these treatments. Although effective and safe anti-obesity drugs are currently available, it is not even partially covered by general health insurance. However, the cost of treatment is unaffordable in the long term for a large proportion of the obese. The virtual unavailability of effective antiobesity drugs for indicated patients has serious health-economic consequences. Failure to take advantage of effective therapeutic options, confirmed by evidence-based medicine, results in a high prevalence of obesity-related diseases, which are even more costly to treat economically and, in the case of type 2 diabetes, even less effective. We consider at least partial reimbursement of antiobesity drugs from general health insurance for cooperating patients under clearly defined conditions to be a necessary step towards improving the situation, and clearly cost-effective in its consequences.

Obesogens in Foods.

Obesogens, as environmental endocrine-disrupting chemicals, are supposed to have had an impact on the prevalence of rising obesity around the world over the last forty years. These chemicals are probably able to contribute not only to the development of obesity and metabolic disturbances in individuals, but also in their progeny, having the capability to epigenetically reprogram genetically inherited set-up points for body weight and body composition control during critical periods of development, such as fetal, early life, and puberty. In individuals, they may act on myriads of neuro-endocrine-immune metabolic regulatory pathways, leading to pathophysiological consequences in adipogenesis, lipogenesis, lipolysis, immunity, the influencing of central appetite and energy expenditure regulations, changes in gut microbiota-intestine functioning, and many other processes. Evidence-based medical data have recently brought much more convincing data about associations of particular chemicals and the probability of the raised risk of developing obesity. Foods are the main source of obesogens. Some obesogens occur naturally in food, but most are environmental chemicals, entering food as a foreign substance, whether in the form of contaminants or additives, and they are used in a large amount in highly processed food. This review article contributes to a better overview of obesogens, their occurrence in foods, and their impact on the human organism.

Chronic DDE Exposure Modifies Mitochondrial Respiration during Differentiation of Human Adipose-Derived Mesenchymal Stem Cells into Mature Adipocytes.

The contribution of environmental pollutants to the obesity pandemic is still not yet fully recognized. Elucidating possible cellular and molecular mechanisms of their effects is of high importance. Our study aimed to evaluate the effect of chronic, 21-day-long, 2,2-bis (4-chlorophenyl)-1,1-dichlorethylenedichlorodiphenyldichloroethylene (p,p'-DDE) exposure of human adipose-derived mesenchymal stem cells committed to adipogenesis on mitochondrial oxygen consumption on days 4, 10, and 21. In addition, the mitochondrial membrane potential (MMP), the quality of the mitochondrial network, and lipid accumulation in maturing cells were evaluated. Compared to control differentiating adipocytes, exposure to p,p'-DDE at 1 µM concentration significantly increased basal (routine) mitochondrial respiration, ATP-linked oxygen consumption and MMP of intact cells on day 21 of adipogenesis. In contrast, higher pollutant concentration seemed to slow down the gradual increase in ATP-linked oxygen consumption typical for normal adipogenesis. Organochlorine p,p'-DDE did not alter citrate synthase activity. In conclusion, in vitro 1 µM p,p'-DDE corresponding to human exposure is able to increase the mitochondrial respiration per individual mitochondrion at the end of adipocyte maturation. Our data reveal that long-lasting exposure to p,p'-DDE could interfere with the metabolic programming of mature adipocytes.

Adult obese patient in primary care.

Overweight and obesity prevalence in middle aged subjects in the Czech Republic is more than 50 per cent, obesity is found in around 26 per cent of population. Obesity management is a long-term and time-consuming process. Early start of the treatment can prevent continuous weight gain and development of co-morbidities. General practitioners see obese patients usually as the first and they represent the first point of contact for adults with obesity. The basis of obesity management is a change of the lifestyle with added pharmacotherapy and/or bariatric/metabolic surgery. The paper presents overview of methods in obesity diagnostics and management and possibilities of their use in GPs daily practice.

Medical nutrition therapy of obesity and its metabolic complications.

Diet therapy of obesity and its metabolic complications is focused on the reversal of chronic positive energy balance, systemic inflammation and adipose tissue dysfunction. The priority in the treatment is caloric restriction together with increased nutritional quality, prevention of nutritional deficits, care of intestinal microbioma, reduction of the organism's exposure to contaminants and increase of the protective components in the diet. The recommended daily energy dose ranges from very low-calorie diets (1.5 to 3 MJ) to low-calorie diets (5 to 7 MJ). According to common EASD and ADA guidelines, the following energy-restricted types of diets are recommended in the management and prevention of metabolic complications of obesity in the form of type 2 diabetes mellitus: Mediterranean, DASH, low-carbohydrate, and vegetarian style of diet. Particular attention is required for the diet following metabolic-bariatric surgery, which is focused on the prevention and treatment of potential nutritional deficits.

Obesity and COVID-19: A Perspective from the European Association for the Study of Obesity on Immunological Perturbations, Therapeutic Challenges, and Opportunities in Obesity.

Accumulating evidence suggests that obesity is a major risk factor for the initiation, progression, and outcomes of coronavirus disease 2019 (COVID-19). The European Association for the Study of Obesity (EASO), as a scientific and medical society dedicated to the promotion of health and well-being, is greatly concerned about the concomitant obesity and COVID-19 pandemics and their impact on health and society at large. In this perspective, we will address the inherent immunological perturbations and alterations in the renin-angiotensin-aldosterone system in patients with obesity and COVID-19, and discuss how these impairments may underlie the increased susceptibility and more detrimental outcomes of COVID-19 in people with obesity. Clearly, this has important implications for preventive measures, vaccination, and future therapeutic strategies to combat COVID-19. Furthermore, we will highlight important knowledge gaps and provide suggestions for future research and recommendations for policy actions. Since many new reports on COVID-19 rapidly appear, the present perspective should be seen as a focus for discussion to drive forward further understanding, research initiatives, and clinical management of COVID-19.

Obesity and COVID-19: The Two Sides of the Coin.

The World Health Organization declared COVID-19, the infectious disease caused by the coronavirus SARS-CoV-2, a pandemic on March 12, 2020. COVID-19 is causing massive health problems and economic suffering around the world. The European Association for the Study of Obesity (EASO) promptly recognised the impact that the outbreak could have on people with obesity. On one side, emerging data suggest that obesity represents a risk factor for a more serious and complicated course of COVID-19 in adults. On the other side, the health emergency caused by the outbreak diverts attention from the prevention and care of non-communicable chronic diseases to communicable diseases. This might be particularly true for obesity, a chronic and relapsing disease frequently neglected and linked to significant bias and stigmatization. The Obesity Management Task Force (OMTF) of EASO contributes in this paper to highlighting the key aspects of these two sides of the coin and suggests some specific actions.

The origin and development of fat droplet and its role in health and illness.

Lipid droplets are found in most cells, where they are needed for lipid metabolism and energy homeostasis. Their biogenesis is still not entirely described process, in which an organelle with monomolecular layer on the surface originates from two-layer membrane of the smooth endoplasmic reticulum. Large lipid droplets can be formed either by growth or by fusion of smaller lipid droplets. Their basic functions are controlled lipid deposition and lipid metabolism and the protection of the intracellular environment from lipotoxicity. Currently, dysfunction of lipid droplet is associated with a number of diseases such as obesity, cardiometabolic syndrome, tumor and neurodegenerative diseases, lipodystrophy and cachexia. Keywords: lipid droplet, adipocyte, endoplasmic reticulum, perilipin, obesity, type 2 diabetes mellitus, lipodystroph.

Effect of n-3 fatty acids supplementation during life style modification in women with overweight.

OBJECTIVE: The marine n-3 fatty acids eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) exert numerous beneficial effects on health, but their potency to defend against development of peripheral insulin resistance of healthy person with overweight remains poorly characterized. We aimed to evaluate the effect of a combination intervention using EPA + DHA and the lifestyle modification (LSM) in women with overweight. METHOD: In a parallel-group, three-arm, randomized trial (UMIN Clinical Trials Registry - R000031131), 34 women were assigned to a 12-week-intervention using corn oil (1.5 g/day; placebo); LSM and corn oil (1.5 g/day; LSM); or LSM and EPA + DHA concentrate (1.5 g/day, containing ~ 0.6 g EPA + DHA; LSM & n-3). At baseline and after intervention, anthropometric measurements including bioelectrical impedance analysis, spiroergometry, 24-hours dietary recall, and various metabolic markers, adiponectin and cytokines were evaluated in serum using standard procedures. Data from 29 women were used for the final evaluation. Wilcoxon two-sided rank-sum test was used to inspect the differences between LSM and LSM & n-3, and placebo groups, with a p-value of ≤ 0.05. All computations were performed with MATLAB Statistics Toolbox. RESULTS: In comparison with placebo, LSM and LSM & n-3 decreased body weight, waist circumference, and body fat, and increased VO2max/kg. LSM & n-3 increased adiponectin levels in comparison to LSM. Fasting insulin, IL8, and cholesterol were decreased by LSM, but were unchanged by LSM & n-3. IL6 was not affected in LSM & n-3, while it was increased in LSM. Other inflammatory markers, as well as leptin, LIF, follistatin, BDNF, and fasting triacylglycerol were not significantly affected by any of the interventions. CONCLUSION: Besides preventing a modest negative effect of LSM on IL6 and adiponectin level, the combination of LSM and EPA + DHA supplementation could be probably used to improve the functional capacity of adipose tissue in women with overweight.

A Proposal of the European Association for the Study of Obesity to Improve the ICD-11 Diagnostic Criteria for Obesity Based on the Three Dimensions Etiology, Degree of Adiposity and Health Risk.

Diagnostic criteria for complex medical conditions caused by a multitude of both genetic and environmental factors should be descriptive and avoid any attribution of causality. Furthermore, the wording used to describe a disorder should be evidence-based and avoid stigmatization of the affected individuals. Both terminology and categorizations should be readily comprehensible for healthcare professionals and guide clinical decision making. Uncertainties with respect to diagnostic issues and their implications may be addressed to direct future clinical research. In this context, the European Association of the Study of Obesity (EASO) considers it an important endeavor to review the current ICD-11 Beta Draft for the definition of overweight and obesity and to propose a substantial revision. We aim to provide an overview of the key issues that we deem relevant for the discussion of the diagnostic criteria. We first discuss the current ICD-10 criteria and those proposed in the ICD 11 Beta Draft. We conclude with our own proposal for diagnostic criteria, which we believe will improve the assessment of patients with obesity in a clinically meaningful way.

Phthalates exposure indicators determined by urinary phthalate metabolites in healthy non-obese Czech adults: FANTOM study.

It is assumed that human exposure to phthalates may be associated with adverse health effects. The indicators of urinary phthalate metabolite concentrations in healthy adults are limited. In this study, the phthalate metabolites concentrations were detected from 24-h urine collection in non-obese Czech adults (n = 201). Each participant filled in an 80-item questionnaire (FANTOM-SQ 2013) regarding the outdoor and indoor sources of phthalates, the use of personal care products and food intake sources. The concentrations of 15 phthalates metabolites were analysed following enzymatic cleavage of the glucuronide using ultra-high-performance liquid chromatography-electrospray ionisation tandem mass spectrometry (UHPLC-ESI-MS/MS). The indicators of chronic or acute exposure phthalate-containing materials were identified. It is shown that higher fruit consumption was positively and significantly associated with a higher level of total 15 urinary phthalates biomarkers (p < 0.001). Regular meat consumption showed a negative significant association with total 15 phthalates metabolites (p < 0.01). The use of personal care products was significantly and positively correlated with monoethyl phthalate urine concentrations (p < 0.05). The analysis of the dietary behaviour and personal care products use in the Czech non-obese population showed it to be a predictable tool in the level of phthalates exposure when high fruit consumption and personal care products use are linked to higher phthalate metabolite contents in the urine. However, this topic deserves more research.

[Potential sources of phthalates and bisphenol A and their significance in the development of metabolic diseases]. / Potenciální zdroje ftalátu a bisfenolu A a jejich význam u metabolických onemocnení.

Nowadays, there is increasing evidence showing that the development of the metabolic syndrome combining obesity, type 2 diabetes mellitus, arterial hypertension and dyslipidemia involves except of traditional risk factors (overnutrition, lack of physical activity, genetic predisposition) also the effect of environmental organic substances called organic pollutants or endocrine disruptors. These chemicals can be found in plastic covers, paints, flame retardants, exhaust gases, fertilizers as well as diverse daily utensils. Phthalates, used primarily as plasticizers, and bisphenol A, are among the most wide-spread members of this group.The aim of this article is to provide a basic overview of the relationship between phthalates and bisphenol A and the etiopathogenesis of the metabolic syndrome and to highlight their potential sources. According to the analysis of materials used for parenteral nutrition and urinary excretion of phthalate metabolites and bisphenol A in subjects on long-term parenteral nutrition we suppose that currently used medical materials are safe with respect to the exposure to both phthalates and bisphenol A and that home environment, especially cosmetic products, might constitute a more probable source of these substances.

Mitochondria in White, Brown, and Beige Adipocytes.

Mitochondria play a key role in energy metabolism in many tissues, including cardiac and skeletal muscle, brain, liver, and adipose tissue. Three types of adipose depots can be identified in mammals, commonly classified according to their colour appearance: the white (WAT), the brown (BAT), and the beige/brite/brown-like (bAT) adipose tissues. WAT is mainly involved in the storage and mobilization of energy and BAT is predominantly responsible for nonshivering thermogenesis. Recent data suggest that adipocyte mitochondria might play an important role in the development of obesity through defects in mitochondrial lipogenesis and lipolysis, regulation of adipocyte differentiation, apoptosis, production of oxygen radicals, efficiency of oxidative phosphorylation, and regulation of conversion of white adipocytes into brown-like adipocytes. This review summarizes the main characteristics of each adipose tissue subtype and describes morphological and functional modifications focusing on mitochondria and their activity in healthy and unhealthy adipocytes.

Urine Levels of Phthalate Metabolites and Bisphenol A in Relation to Main Metabolic Syndrome Components: Dyslipidemia, Hypertension and Type 2 Diabetes. A Pilot Study.

AIM: Human exposure to organic pollutants (some of them also called endocrine disruptors) can be associated with adverse metabolic health outcomes including type 2 diabetes. The goal of this study was to compare the urine levels of bisphenol A and phthalate metabolites in subgroups of patients with metabolic syndrome composed of patients with and without three important components of metabolic syndrome (hypertension, dyslipidemia and diabetes). METHODS: We have investigated 24 hr urine samples of 168 patients with metabolic syndrome from the Metabolic Outpatient Department of General University Hospital in Prague. Using standard metabolic syndrome criteria, we classified patients as dyslipidemic (n=87), hypertensive (n=96), and type 2 diabetic (n=58). Bisphenol A and 15 metabolites of phthalates were evaluated in relation to creatinine excretion. Samples were analysed with enzymatic cleavage of glucuronide using ultra-high-performance liquid chromatography-electrospray ionization tandem mass spectrometry in one laboratory with external quality control. RESULTS: Four metabolites, mono-n-butyl phthalate, mono-(2-ethyl-5-hydroxyhexyl) phthalate, mono-(2-ethyl-5-oxohexyl) phthalate, and mono-(2-ethyl-5-carboxypentyl) phthalate showed significantly higher levels in diabetic compared to non-diabetic patients (p<0.001, p=0.002, p=0.002, and p=0.005, respectively). The differences remained significant after adjustment to hypertension, dyslipidemia, age, and BMI. No difference was found between either the hypertensive and non-hypertensive or dyslipidemic and non-dyslipidemic patients. There was no significant relation of bisphenol A level to diabetes, hypertension, dyslipidemia, age, and BMI. CONCLUSIONS: Urine levels of four phthalate metabolites were significantly higher in type 2 diabetics independently on specified predictors. Phthalate levels can be in relation to beta cell dysfunction in type 2 diabetic patients but this study is not able to show if the relation is causal.

PERSISTENT ORGANOCHLORINE POLLUTANTS IN OBESE WOMEN AFTER DIET INDUCED WEIGHT LOSS: FIVE YEARS FOLLOW UP STUDY.

AIM: Persistent organochlorine pollutants (POPs) from the environment are still bioaccumulating in human tissues. The aim of our study was to analyze the development of plasma POPs levels in obese women in relationship with their weight loss success in five year follow-up study. METHODS: 20 obese women aged 25-73 years were studied just before and after having completed a 3 month controlled low calorie diet (LCD) intervention (5 MJ daily), and again after 6 and 60 months since the beginning of the study. Body weight and plasma levels of 7 POPs were measured: polychlorinated biphenyls (PCB) 153, 138, 180; 2,2-bis(4-chlorophenyl)-1,1,1-trichloroethylene (p,p'-DDE); 2,2-bis(4-chlorophenyl)-1,1,1-trichloroethane (p,p'-DDT), hexachlorocyclobenzene (HCB), hexachlorocyclohexane ß (HCH ß). RESULTS: Data shows that after 3 months of a completely controlled restrictive diet regimen, the weight loss was associated with an increase in POP plasma levels. However, after a five year follow-up, there were no differences in POPs plasma levels between those who kept losing weight or maintained the initial weight (WL/M) and the group of weight gainers (WG), except for HCB where the WG had a significantly higher level (p < 0.05). CONCLUSIONS: These results suggest that contrary to the long-term weight gain, the long-term weight loss or weight maintenance caused by diet restriction is associated with lower plasma levels of HCB.

Dramatic decrease in muscular fitness in the Czech schoolchildren over the Last 20 years.

AIM: Obesity and physical inactivity had already reached epidemic, becoming one of the leading causes of death and disability worldwide. The objective of this study was to investigate the current level and a nearly three decades' trend of muscular fitness (MF) and the nutritional state of Czech children. METHODS: In 2013, cross-sectional epidemiological survey was conducted in schoolchildren with examination of the anthropometric characteristics and measured MF using a UNIFIT test, which normative for MF categories was given as results of national monitoring data collected in 1987. In total 896 current schoolchildren (472 aged 8-9 years and 424 aged 12-13 years) were examined from selected children through stratified sampling from the Czech Republic. RESULTS: Against 31% of children from 1986 there were 74% of current children classified as "poor" or "below normal" in the MF category (p<0.001). MF was inversely associated with BMI. Poor posture was diagnosed in 24% of children, more frequently in overweight (OW) and obese (OB) children in comparison to normal body weight children (p<0.001). In comparison to 10% of OW and OB children in 1991, using these cut-off points for body mass index references, the current prevalence of OW and OB doubled (19.8%). CONCLUSIONS: Current Czech schoolchildren showed a doubled prevalence of OW and OB during the last two decades and simultaneously during nearly three decades there were more than doubled prevalence of "poor" or "under normal" MF of children, with overall dramatic decrease of MF in current schoolchildren.

Heavy metals in hair samples: a pilot study of anaemic children in Kazakhstan, Kyrgyzstan and Uzbekistan.

BACKGROUND: Heavy metals with their potential haematotoxic effect can contribute to the risks of anaemia in children in the Central Asian Republics (CAR), where burden and exposure to these metals is still not sufficiently known and reported. METHODS: Cross-sectional study was performed in Central Asian countries in hospitals in Kazakhstan, Kyrgyzstan and Uzbekistan with the aim to investigate the potential contribution of heavy metals to anaemia in children. In each country, 20 children were recruited, all were hospitalised with diagnosed anaemia. A sample of hair was taken from each child to assess the hair concentration of lead, cadmium and mercury. RESULTS: Relatively high levels of hair lead were observed, particularly in Kyrgyzstan. While lead and cadmium concentrations did not differ significantly among countries, mercury was lower in Kazakhstan than in Kyrgyzstan (p < 0.05) and Uzbekistan (p < 0.001). Hair lead and cadmium levels were significantly positively correlated (correlation coefficient = 0.51, p < 0.001). CONCLUSION: The results of this study showed higher than expected levels of hair lead, cadmium and mercury in anaemic children. Because iron deficiency anaemia is a major public health problem in CAR, further investigation of the extent of exposure to heavy metal and its contribution in iron deficiency anaemia in the region would be recommended.

[Obesity prevention]. / Prevence obezity.

Obesity is chronic disease, with increased prevalence since sixties of last century, now widespread as well in developing countries, not only in developed countries, like on the beginning. Obesity with its co-morbidities reduces longitude and quality of life. Treatment and indirect costs of obesity are rising and economically demanding. At present time there are not sufficient data supporting effectiveness of specific community preventive intervention. Interventional activity being in progress are based on active mobilization of citizens to active life style, with healthy diet and increased physical activity, with effort to build up anti-obese physical environment, helpful to making healthy choice much easier. Results of so far conducted preventive interventions are biased by the fact, that implemented strategies are limited not only to target population, but as well widespread to control population. Their effects could be probably expected in future, like it happened in the most successful the North Karelia project preventing cardiovascular mortality. There is given description of possible preventive strategies fighting obesity in the Czech Republic as well.