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.

The impact of metabolic endotoxaemia on the browning process in human adipocytes.

BACKGROUND: Dysfunctional adipose tissue (AT) is known to contribute to the pathophysiology of metabolic disease, including type 2 diabetes mellitus (T2DM). This dysfunction may occur, in part, as a consequence of gut-derived endotoxaemia inducing changes in adipocyte mitochondrial function and reducing the proportion of BRITE (brown-in-white) adipocytes. Therefore, the present study investigated whether endotoxin (lipopolysaccharide; LPS) directly contributes to impaired human adipocyte mitochondrial function and browning in human adipocytes, and the relevant impact of obesity status pre and post bariatric surgery. METHODS: Human differentiated abdominal subcutaneous (AbdSc) adipocytes from participants with obesity and normal-weight participants were treated with endotoxin to assess in vitro changes in mitochondrial function and BRITE phenotype. Ex vivo human AbdSc AT from different groups of participants (normal-weight, obesity, pre- and 6 months post-bariatric surgery) were assessed for similar analyses including circulating endotoxin levels. RESULTS: Ex vivo AT analysis (lean & obese, weight loss post-bariatric surgery) identified that systemic endotoxin negatively correlated with BAT gene expression (p < 0.05). In vitro endotoxin treatment of AbdSc adipocytes (lean & obese) reduced mitochondrial dynamics (74.6% reduction; p < 0.0001), biogenesis (81.2% reduction; p < 0.0001) and the BRITE phenotype (93.8% reduction; p < 0.0001). Lean AbdSc adipocytes were more responsive to adrenergic signalling than obese AbdSc adipocytes; although endotoxin mitigated this response (92.6% reduction; p < 0.0001). CONCLUSIONS: Taken together, these data suggest that systemic gut-derived endotoxaemia contributes to both individual adipocyte dysfunction and reduced browning capacity of the adipocyte cell population, exacerbating metabolic consequences. As bariatric surgery reduces endotoxin levels and is associated with improving adipocyte functionality, this may provide further evidence regarding the metabolic benefits of such surgical interventions.

Waist circumference and waist-to-height ratio in 7-year-old children-WHO Childhood Obesity Surveillance Initiative.

Childhood obesity is a serious global health problem. Waist circumference (WC) and waist-to-height ratio (WHtR) reflect body fat distribution in children. The objectives of this study were to assess WC and WHtR in 7-year-old children and to determine body mass index (BMI), WC, and WHtR differences in children from 10 selected countries across Europe (Bulgaria, Czechia, Greece, Ireland, Latvia, Lithuania, North Macedonia, Norway, Spain, and Sweden) participating in the World Health Organization (WHO) Europe Childhood Obesity Surveillance Initiative (COSI). The 50th and 90th percentile of WC (according to COSI and "Identification and prevention of Dietary- and lifestyle-induced health EFfects In Children and infantS" (IDEFICS) cutoff values) and WHtR above 0.5 were used as measures of abdominal obesity in a unique sample of 38,975 children aged 7.00-7.99 years. Southern European countries, including Greece and Spain, showed significantly higher BMI, WC, and WHtRin both genders (p < 0.0001) than Eastern and Northern Europe. The highest values for WC were observed in Greece (60.8 ± 7.36 cm boys; 60.3 ± 7.48 cm girls), North Macedonia (60.4 ± 7.91 cm boys; 59.0 ± 8.01 cm girls), and Spain (59.7 ± 6.96 cm boys; 58.9 ± 6.77 cm girls). WC and WHtRin may add an information about the occurrence of central obesity in children.

FADS1 gene polymorphism(s) and fatty acid composition of serum lipids in adolescents.

Polyunsaturated fatty acids (PUFA) influence many physiological functions. Associations have been found between single nucleotide polymorphisms (SNP) in the FADS1 (Fatty acid desaturase 1) gene and the relative abundance of PUFA in serum lipids. This study examines the relationship between two SNPs in the FADS1 gene (rs174546, rs174537) and the fatty acid (FA) composition of serum lipids in adolescents (13-18 years). We used DNA samples (670 children; 336 girls and 334 boys) from the Childhood Obesity Prevalence and Treatment (COPAT) project. Genomic DNA was extracted from peripheral blood leukocytes in whole blood samples. For genotype analysis, TaqMan SNP Genotyping assays (Applied Biosystems) were used. Fatty acid composition of serum lipids was assessed using gas chromatography. The T-statistic and regression were used for statistical evaluations. Minor allele T carriers in both SNPs had significant lower level of palmitic acid (16:0, phospholipids) and arachidonic acid (20:4[n-6], phospholipids) in both sexes. In girls, we found a significant positive association between minor allele T carriers and eicosadienoic acid (20:2[n-6], cholesteryl esters) in both SNPs. Being a minor allele T carrier was significantly positively associated with dihomo-γ-linolenic acid (20:3[n-6], phospholipids) in boys in both SNPs. SNPs (including rs174546, rs174537) in the FADS gene cluster should have impacted desaturase activity, which may contribute to different efficiency of PUFA synthesis.

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.

Acipimox Administration With Exercise Induces a Co-feedback Action of the GH, PP, and PYY on Ghrelin Associated With a Reduction of Peripheral Lipolysis in Bulimic and Healthy-Weight Czech Women: A Randomized Study.

Objective: Anti-lipolytic drugs and exercise are enhancers of growth hormone (GH) secretion. Decreased circulating free fatty acids (FFA) have been proposed to exert ghrelin-GH feedback loop after administration of an anti-lipolytic longer-acting analog of nicotinic acid, Acipimox (OLB, 5-Methylpyrazine-2-carboxylic acid 4-oxide, molecular weight of 154.1 Da). OLB administration strongly suppresses plasma FFA during exercise. Neuroendocrine perturbations of the adipose tissue (AT), gut, and brain peptides may be involved in the etiopathogenesis of eating disorders including bulimia nervosa (BN) and anorexia nervosa. BN is characterized by binge eating, self-induced vomiting or excessive exercise. Approach: To test the hypothesis that treatment with OLB together with exercise vs. exercise alone would induce feedback action of GH, pancreatic polypeptide (PP), peptide tyrosine tyrosine (PYY), and leptin on ghrelin in Czech women with BN and in healthy-weight Czech women (HW). The lipolysis rate (as glycerol release) in subcutaneous abdominal AT was assessed with microdialysis. At an academic medical center, 12 BN and 12 HW (the control group) were randomized to OLB 500 mg 1 h before a single exercise bout (45 min, 2 W/kg of lean body mass [LBM]) once a week vs. identical placebo over a total of 2 weeks. Blood plasma concentrations of GH, PP, PYY, leptin, ghrelin, FFA, glycerol, and concentrations of AT interstitial glycerol were estimated during the test by RIA utilizing 125I-labeled tracer, the electrochemiluminescence technique (ECLIA) or colorimetric kits. Results: OLB administration together with short-term exercise significantly increased plasma GH (P < 0.0001), PP (P < 0.0001), PYY, and leptin concentrations and significantly decreased plasma ghrelin (P < 0.01) concentrations in both groups, whereas short-term exercise with placebo resulted in plasma ghrelin (P < 0.05) decrease exclusively in BN. OLB administration together with short-term exercise significantly lowered local subcutaneous abdominal AT interstitial glycerol (P < 0.0001) to a greater extent in BN. Conclusion: OLB-induced suppression of plasma ghrelin concentrations together with short-term exercise and after the post-exercise recovering phase suggests a potential negative co-feedback of GH, PP, PYY, and leptin on ghrelin secretion to a greater extent in BN. Simultaneously, the exercise-induced elevation in AT interstitial glycerol leading to a higher inhibition of peripheral lipolysis by OLB in BN. Clinical Trial Registration: www.ClinicalTrials.gov, identifier NCT03338387.

Insulin sensitivity and its relation to hormones in adolescent boys and girls.

BACKGROUND AND AIMS: A subset of obese individuals lacks cardiometabolic impairment. We aimed to analyze hormonal profiles of insulin-sensitive obese (ISO) and insulin-resistant obese (IRO) adolescents and determine hormonal predictors of homeostasis model of insulin resistance (HOMA-IR). MATERIALS AND METHODS: A threshold of 3.16 of HOMA-IR was used to classify ISO (<3.16) IRO (≥3.16). In 702 individuals aged 13-18years (55.8% girls) anthropometric and laboratory [blood glucose, insulin, thyrotropin (TSH), free thyroxine (fT4), free triiodothyronine (fT3), sex hormone-binding globulin (SHBG), steroid hormones, luteinizing hormone, follicle stimulating hormone, prolactin, ghrelin, glucose-dependent insulinotropic polypeptide, glucagon-like-peptide 1glucagon, leptin, resistin, visfatin, leptin, adiponectin and adipsin] assessments were performed. Orthogonal projections to latent structures and Mann-Whitney tests with Bonferroni correction were applied for statistical analysis. RESULTS: 52.6% girls and 42.9% boys were insulin sensitive. In the predictive model of HOMA-IR thyroid function tests, adiponectin, ghrelin and leptin concentrations played an important role in both genders. Prolactin, testosterone and glucagon contributed to the model only in boys, while progesterone and dehydroepiandrosterone sulfate levels only in girls. After Bonferroni correction levels of leptin, adiponectin, leptin/adiponectin ratio, SHBG and fT4/TSH ratio in both genders, testosterone and glucagon levels in boys and levels of TSH and fT3 in girls were related to insulin sensitivity. CONCLUSION: Metabolic health defined by HOMA-IR is partly predicted by various hormones. Some of them are gender specific. Free T4/TSH and leptin/adiponectin ratios are related to insulin sensitivity in both genders.

Insulin Sensitivity and Secretion in Obese Type 2 Diabetic Women after Various Bariatric Operations.

OBJECTIVE: To compare the effects of biliopancreatic diversion (BPD) and laparoscopic gastric banding (LAGB) on insulin sensitivity and secretion with the effects of laparoscopic gastric plication (P). METHODS: A total of 52 obese women (age 30-66 years) suffering from type 2 diabetes mellitus (T2DM) were prospectively recruited into three study groups: 16 BPD; 16 LAGB, and 20 P. Euglycemic clamps and mixed meal tolerance tests were performed before, at 1 month and at 6 months after bariatric surgery. Beta cell function derived from the meal test parameters was evaluated using mathematical modeling. RESULTS: Glucose disposal per kilogram of fat free mass (a marker of peripheral insulin sensitivity) increased significantly in all groups, especially after 1 month. Basal insulin secretion decreased significantly after all three types of operations, with the most marked decrease after BPD compared with P and LAGB. Total insulin secretion decreased significantly only following the BPD. Beta cell glucose sensitivity did not change significantly post-surgery in any of the study groups. CONCLUSION: We documented similar improvement in insulin sensitivity in obese T2DM women after all three study operations during the 6-month postoperative follow-up. Notably, only BPD led to decreased demand on beta cells (decreased integrated insulin secretion), but without increasing the beta cell glucose sensitivity.

[Are the thyroid hormones and thyrotropin associated with cardiometabolic risks and insulin resistance even in euthyroid subjects?] / Jsou tyreoidální hormony a tyreotropin asociovány s kardiometabolickými riziky a inzulinovou rezistencí u eutyreoidních jedincu?

Associations of both hypothyroidism and subclinical hypothyroidism with metabolic syndrome are well established. Nowadays, more attention has been paid to the role of thyroid hormones and thyrotropin (TSH) within the euthyroid range on the development of cardiometabolic health risks. The paper summarizes current knowledge related to the associations of lower free thyroxine (fT4) level and higher levels of both free triiodothyronine (fT3) and TSH with body adiposity, metabolic syndrome and insulin resistance in euthyroid subjects. In our recent study of obese euthyroid adolescents, we revealed that fasting insulin and homeostasis model assessment of insulin resistance (HOMA-IR) positively correlated with fT3 and TSH and negatively with fT4. The ratio of fT3 to fT4 was also significantly related to HOMA-IR both in girls (r = 0.347, p < 0.001) and boys (r = 0.267, p < 0.001). It is concluded that up-to-date conducted studies mostly confirmed that thyroid hormones and TSH even in euthyroid range may significantly affect the metabolic health and particularly insulin sensitivity.Key words: euthyroid range - insulin resistance - metabolic health - metabolic syndrome - obesity - thyrotropin - thyroxine - triiodothyronine.

Cardiometabolic Health in Obese Adolescents Is Related to Length of Obesity Exposure: A Pilot Study.

CONTEXT: Metabolically healthy obesity (MHO) is found in a subset of obese individuals. OBJECTIVE: This study sought to examine possible determinants of MHO related to the length of exposure to obesity, lifestyle factors, and dietary intake in adolescent boys. DESIGN: This was a cross-sectional Childhood Obesity Prevalence And Treatment study. Participants and Main Measures: Of 313 boys age 13.0-17.9 years with a body mass index (BMI) ≥ 97th percentile for age, two study cohorts were established based on two definitions of metabolically unhealthy obesity (MUO). Cohort 1 included 18 boys with at least three risk factors (hypertension, dyslipidemia, dysglycemia) who were matched for age, weight, height, and BMI with 18 boys with MHO. Cohort 2 included 35 boys with at least two risk factors who were compared with 31 boys with MHO. MHO was defined by the absence of cardiometabolic risk factors (excluding waist). Data on lifestyle factors and BMI growth trajectories were compared (MHO vs MUO). RESULTS: Boys with MUO (Cohort 1) presented with an earlier onset (4.3 vs 9.1 y; P = .005) and a longer duration of obesity (11.2 vs 6.4 y; P = .003) compared with those with MHO in both group comparisons using different MUO definitions. We found an overall trend toward higher BMI z scores (significant from 3-7 y; P < .001) in metabolically unhealthy compared with their healthy counterparts (Cohort 1). Boys with MHO had higher carbohydrate intake (P < .001). No additional determinants of MHO were observed. CONCLUSIONS: Increased cardiometabolic risk in boys is related to an earlier onset and a longer duration of obesity.

A common variant near BDNF is associated with dietary calcium intake in adolescents.

Specific targets for most obesity candidate genes discovered by genomewide association studies remain unknown. Such genes are often highly expressed in the hypothalamus, indicating their role in energy homeostasis. We aimed to evaluate the associations of selected gene variants with adiposity and dietary traits. Anthropometric parameters, fat mass, dietary intake (total energy, fat, protein, carbohydrate, fiber, and calcium) and 10 gene variants (in/near TMEM18, SH2B1, KCTD15, PCSK1, BDNF, SEC16B, MC4R and FTO) were analyzed in 1953 Czech individuals aged 10.0 to 18.0 years (1035 nonoverweight and 918 overweight: body mass index [BMI] ≥90th percentile). Obesity risk alleles of TMEM18 rs7561317, SEC16B rs10913469, and FTO rs9939609 were related to increased body weight and BMI (P < .005). The FTO variant also showed a significant positive association with waist circumference and fat mass (P < .001). Overweight adolescents had a lower total energy intake (P < .001) but a higher percentage of fat (P = .009) and protein intake (P < .001) than the nonoverweight subjects. There was also a lower calcium intake in the overweight group (P < .001). An association with at least one component of dietary intake was found in 3 of 10 studied gene variants. The MC4R rs17782313 was associated negatively with protein (P = .012) and positively associated with fiber (P = .032) intakes. The obesity risk alleles of BDNF rs925946 and FTO rs9939609 were related to a lower calcium intake (P = .001 and .037). The effects of FTO and MC4R variants, however, disappeared after corrections for multiple testing. Our results suggest that the common BDNF variant may influence dietary calcium intake independent of BMI.

Glucose homeostasis and insulin resistance: prevalence, gender differences and predictors in adolescents.

BACKGROUND: Adolescence, due to transient pubertal insulin resistance (IR), is associated with a higher risk for disturbances of glucose metabolism. The aim of our study was 1) to investigate the prevalence of disturbances of glucose metabolism, 2) to define gender specific homeostasis model assessment of insulin resistance (HOMA-IR) thresholds associated with increased cardiometabolic risks and 3) to provide predictors of HOMA-IR. METHODS: The studied cohort consisted of Czech adolescents aged 13.0-17.9 years: 1,518 individuals of general population and three studied groups according weight category (615 normal weight, 230 overweight and 683 obese). The prevalence of IR, impaired fasting glucose (IFG) and type 2 diabetes was assessed. Risky HOMA-IR thresholds based on components of metabolic syndrome were investigated. HOMA-IR prediction was calculated taking into account age, blood pressure, multiple anthropometric, biochemical and hormonal parameters. RESULTS: In general population cohort, the prevalence of IFG and type 2 diabetes was 7.0% and <0.5%, respectively. Boys regardless of weight presented significantly higher levels of blood glucose and higher prevalence of IFG than girls. Obese boys were found more insulin resistant than obese girls. HOMA-IR thresholds of 3.6 for girls and 4.4 for boys were associated with increased cardiometabolic risks. For both genders, the model of HOMA-IR prediction was composed of age, BMI, ratio of free triiodthyronine to free thyroxine, gamma-glutamyltransferase activity and levels of triglycerides and sex hormone-binding globulin. CONCLUSIONS: The type 2 diabetes in adolescents, including those who were obese, was rarely diagnosed. Obese adolescent boys were at greater risk for IR and for IFG than obese girls. In adolescence, thresholds of HOMA-IR in contrast to predictors were found gender specific.

[Genetic background in common forms of obesity - from studies on identical twins to candidate genes of obesity]. / Genetické pozadí bezných forem obezity - od studií identických dvojcat po studium kandidátních genu obezity*

Common obesity is a result of interaction between genes and environmental/lifestyle factors, with heritability estimates 40-70%. Not only the susceptibility to obesity but also the success of weight management depends on the genetic background of each individual. This paper summarizes the up-to-date knowledge on genetic causes of common obesities. Introduction of genome-wide association studies (GWAS) led to an identification of a total of 32 variants associated with obesity/BMI and 14 with body fat distribution. Further, a great progress in revealing the mechanisms regulating the energy balance was also noted. However, the proportion of explained variance for BMI is still low, suggesting other mechanisms such as gene-gene and gene-environment interactions, rare gene variants, copy number variants polymorphisms, or epigenetic modifications and microRNAs regulating gene transcription. In summary, we present results of our studies on obesity risk variants in Czech adults, children and adolescents including those evaluating the influence of selected gene variants on the outcomes of weight management.

Overview of new antiobesity drugs.

A short overview of new drugs approved for the treatment of obesity (lorcaserin, phentermine/topiramate combination) as well as those with a perspective for approval as antiobesity drugs (cetilistat, naltrexone/bupropion combination, liraglutide) is presented. All these drugs produce significant weight loss accompanied by reductions in cardiometabolic health risks. Although the adverse events were rather rare and tended to decrease with the duration of treatment with most of these medications, the drug-specific safety concerns should be seriously considered. In order to ensure an appropriate, efficient and safe implementation of novel antiobesity drugs into the comprehensive treatment of obesity, it will be necessary to establish a network of physicians and other health-care providers well educated in obesity management.

Tolerability and safety of the new anti-obesity medications.

Worldwide obesity prevalence has nearly doubled since 1980. Due to numerous co-morbidities, obesity represents a serious health and socioeconomic problem worldwide. Pharmacotherapy should be an integral part of comprehensive obesity management. Drug therapy can assist in weight loss and its maintenance in those individuals who do not achieve appropriate weight loss through lifestyle interventions alone. After the withdrawal of sibutramine from the market in 2010, orlistat, a lipase inhibitor, was the only remaining prescription drug approved for the long-term treatment of obesity. In 2012, phentermine/topiramate extended-release (PHEN/TPM ER) combination and lorcaserin were approved by the US FDA as novel medications for long-term weight management. Three major phase III trials conducted with each drug confirmed their efficacy in terms of weight loss/maintenance and improvement of cardiometabolic risks. No head-to-head studies between the two new anti-obesity drugs have been carried out. However, in the existing studies PHEN/TPM ER had a superior weight loss profile to lorcaserin but the incidence of adverse effects was lower with lorcaserin. Both drugs were well-tolerated, and adverse events were modest in intensity, dose dependent, rather rare, and tended to decrease with the duration of treatment. Major safety concerns regarding PHEN/TPM ER include elevations in resting pulse rate, teratogenicity, mild metabolic acidosis, and psychiatric and cognitive adverse events. Valvulopathy, cognitive impairment, psychiatric disorders, and hypoglycemia represent major safety concerns for lorcaserin. Although existing trials have not demonstrated any significant issues with PHEN/TPM ER-induced heart rate elevation and lorcaserin-induced valvulopathy, all safety concerns should be seriously taken into account in patients treated with either of these novel anti-obesity medications.

Laparoscopic greater curvature plication in morbidly obese women with type 2 diabetes: effects on glucose homeostasis, postprandial triglyceridemia and selected gut hormones.

BACKGROUND: Laparoscopic greater curvature plication (LGCP) is an emerging bariatric procedure that reduces the gastric volume without implantable devices or gastrectomy. The aim of this study was to explore changes in glucose homeostasis, postprandial triglyceridemia, and meal-stimulated secretion of selected gut hormones [glucose-dependent insulinotropic polypeptide (GIP), glucagon-like peptide-1 (GLP-1), ghrelin, and obestatin] in patients with type 2 diabetes mellitus (T2DM) at 1 and 6 months after the procedure. METHODS: Thirteen morbidly obese T2DM women (mean age, 53.2 ± 8.76 years; body mass index, 40.1 ± 4.59 kg/m2) were prospectively investigated before the LGCP and at 1- and 6-month follow-up. At these time points, all study patients underwent a standardized liquid mixed-meal test, and blood was sampled for assessment of plasma levels of glucose, insulin, C-peptide, triglycerides, GIP, GLP-1, ghrelin, and obestatin. RESULTS: All patients had significant weight loss both at 1 and 6 months after the LGCP (p ≤ 0.002), with mean percent excess weight loss (%EWL) reaching 29.7 ± 2.9% at the 6-month follow-up. Fasting hyperglycemia and hyperinsulinemia improved significantly at 6 months after the LGCP (p < 0.05), with parallel improvement in insulin sensitivity and HbA1c levels (p < 0.0001). Meal-induced glucose plasma levels were significantly lower at 6 months after the LGCP (p < 0.0001), and postprandial triglyceridemia was also ameliorated at the 6-month follow-up (p < 0.001). Postprandial GIP plasma levels were significantly increased both at 1 and 6 months after the LGCP (p < 0.0001), whereas the overall meal-induced GLP-1 response was not significantly changed after the procedure (p > 0.05). Postprandial ghrelin plasma levels decreased at 1 and 6 months after the LGCP (p < 0.0001) with no significant changes in circulating obestatin levels. CONCLUSION: During the initial 6-month postoperative period, LGCP induces significant weight loss and improves the metabolic profile of morbidly obese T2DM patients, while it also decreases circulating postprandial ghrelin levels and increases the meal-induced GIP response.

The role of "mixed" orexigenic and anorexigenic signals and autoantibodies reacting with appetite-regulating neuropeptides and peptides of the adipose tissue-gut-brain axis: relevance to food intake and nutritional status in patients with anorexia nervosa and bulimia nervosa.

Eating disorders such as anorexia (AN) and bulimia nervosa (BN) are characterized by abnormal eating behavior. The essential aspect of AN is that the individual refuses to maintain a minimal normal body weight. The main features of BN are binge eating and inappropriate compensatory methods to prevent weight gain. The gut-brain-adipose tissue (AT) peptides and neutralizing autoantibodies play an important role in the regulation of eating behavior and growth hormone release. The mechanisms for controlling food intake involve an interplay between gut, brain, and AT. Parasympathetic, sympathetic, and serotoninergic systems are required for communication between brain satiety centre, gut, and AT. These neuronal circuits include neuropeptides ghrelin, neuropeptide Y (NPY), peptide YY (PYY), cholecystokinin (CCK), leptin, putative anorexigen obestatin, monoamines dopamine, norepinephrine (NE), serotonin, and neutralizing autoantibodies. This extensive and detailed report reviews data that demonstrate that hunger-satiety signals play an important role in the pathogenesis of eating disorders. Neuroendocrine dysregulations of the AT-gut-brain axis peptides and neutralizing autoantibodies may result in AN and BN. The circulating autoantibodies can be purified and used as pharmacological tools in AN and BN. Further research is required to investigate the orexigenic/anorexigenic synthetic analogs and monoclonal antibodies for potential treatment of eating disorders in clinical practice.