Postprandial Triglyceride, Glucose and Insulin Levels 10 Years After Bariatric Surgery in Women With Severe Obesity - A Pilot Study: Part 1 - Laparoscopic Greater Curvature Plication.

The long-term effects of bariatric surgery on postprandial profiles in patients with obesity and type 2 diabetes (T2D) have not yet been investigated. Therefore, this study examined postprandial profiles before laparoscopic greater curvature plication (LGCP), and then at 2 and 10 years after surgery.The studied cohort included 10 women (mean age= 54.4±5 years) with obesity (mean BMI= 42.5±7.8 kg/m?) and T2D who underwent LGCP. All subjects underwent a standardized liquid mixed-meal test. For statistical evaluation, ANOVA with Bonferroni multiple comparison was used. Mean postprandial levels were significantly decreased 2 years after surgery. Responses 10 years after the surgery also remained significantly lower than before surgery. Changes observed during the follow-up were significant: glucose: F=34.5, p<0.001; insulin: F=49.3, p<0.001; triglycerides F=9.2, p<0.001. The long-term favorable effects of bariatric surgery on cardiometabolic health may be partly mediated by reductions in postprandial glucose, insulin, and triglyceride levels.

Postprandial Triglyceride, Glucose and Insulin Levels 10 Years After Bariatric Surgery in Women With Severe Obesity - A Pilot Study: Part 2 - Biliopancreatic Diversion.

Obesity significantly increases the risk of developing metabolic and cardiovascular diseases. The most effective management tool for both obesity and type 2 diabetes (T2D) is bariatric/metabolic surgery. Delayed postprandial plasma triglyceride clearance contributes to the development of atherosclerosis in patients with T2D. Biliopancreatic diversion (BPD) was shown to be the most effective procedure in long-term T2D remission. However, the effect of BPD on postprandial metabolic profile has not been studied so far. In this pilot study, we therefore examined the changes in postprandial glucose, insulin, and triglyceride in women with severe obesity and T2D before surgery and then two and ten years after BPD. The studied cohort included 7 women (mean age at baseline=49.3±8.2 years) with severe obesity (mean BMI= 45.7±2.9 kg/m?) and T2D. A standardized liquid mixed-meal test was carried out in all subjects and the mean postprandial levels of plasma glucose, insulin, and triglyceride were analyzed by standard laboratory procedures. For statistical evaluation, ANOVA with Bonferroni multiple comparisons was used. Ten years after BPD not only a significant reduction of an average BMI (F=32.9, p<0.001) but also significant declines in mean postprandial plasma levels of glucose (F=155.3, p<0.001), insulin (F=69.8, p<0.001), and triglyceride (F=139.9, p<0.001) were demonstrated. The observed changes in postprandial metabolic profile may contribute to improved cardiometabolic health after bariatric surgery.

The fatty acid composition of serum phospholipids in adolescents is associated with body composition in early adulthoods: an eight-year follow-up study.

The fatty acid composition is associated with obesity. Omega 3 polyunsaturated fatty acid (PUFA) could have a beneficial role in the prevention and treatment of many disorders, including cardiometabolic diseases. A cohort of 84 men and 131 women were examined in adolescence and after 8 years. Body weight (BW) and fat mass (FM) were measured. The composition of fatty acids (FAs) of serum phospholipids was assessed using gas chromatography. Statistics: PLS method. Aim: to determine the relationships between FAs in adolescence and FM (explanatory variable 1, EV1) and BW (explanatory variable 2, EV2) in adulthood. In the predictive models, a cluster of FAs in boys explained 47.2 % of EV1 and a cluster of 6 FAs in girls explained 32.3 % of EV1 measured in adulthood. FAs measured in adolescents explained 23.7 % of EV2 in early adults regardless of gender. A significant negative association was found between 18:1n-9c and EV1 in males and EV2 in both genders. We found a significant negative association between 18:2n-6 and 20:0 and both EV1 and EV2. In all analyses, we found a significant negative association of 20:1n-9 and 18:3n-3 with EV1-2 in both genders. A significant positive association was found in 20:3n-6 with EV1 and EV2 in males. 20:4n-6 was positively associated with EV1 in females and EV2 in both genders. A positive association between FM and very long chain n- 6 PUFAs was also observed. It is concluded that serum MUFAs and essential PUFAs in adolescence are associated with lower BW and FM in adulthood.

Melanocortin pathways: suppressed and stimulated melanocortin-4 receptor (MC4R).

Leptin-melanocortin pathway plays an essential role in the body weight regulation. Enhanced melanocortin signaling in the hypothalamus results in both decreased food intake and increased energy expenditure. The discovery of monogenic obesities with dysfunction of melanocortin-4 receptor (MC4R) greatly contributed to understanding of energy balance regulation. This review presents phenotypical characterization and prevalence of the MC4R gene mutations. Genome-wide association studies revealed that MC4R gene is significantly related not only to monogenic obesities but also to common obesity. An interaction of variants in the MC4R gene with fat mass and obesity associated (FTO) gene significantly increases the risk for obesity, particularly in adolescence. On the other hand, about 15 % of the MC4R gene variants result in a gain of function that protects against obesity and is associated with favorable metabolic profile. Long-term attempts to activate the MC4R have recently been finalized by a discovery of setmelanotide, a novel specific MC4R agonist that is devoid of untoward cardiovascular side-effects. The employment of specific MC4R agonists may open new horizons not only in the treatment of rare monogenic obesities but also in some common obesities where stimulation of MC4R could be achieved.

Links between the circadian rhythm, obesity and the microbiome.

Obesity is linked to a wide range of serious illnesses. In addition to the important impact on the health of the individual, obesity also has a substantial impact on the economy. Disruption of physiological day-night cycles could contribute to the increased incidence of obesity. According to the American National Sleep Federation, the percentage of the people who reported a sleep duration of six hours or less increased from 12 to 37 % over ten years. Insufficient sleep leads not only to an increase of the total calorie intake but changes the meal preference in favor of palatable foods and meals with high carbohydrate content. A decrease of leptin and increase of ghrelin levels caused by sleep deficiency can also play a role. In addition to the higher caloric intake, the timing of food consumption should be taken into account. The same meal eaten during the night versus the day is associated with increased postprandial glucose and triglyceride levels. The gut microbiome has also been recently understood as an endocrine system, with links between the gut microbiome and circadian rhythm changes possibly influencing increased obesity.

Impact of dietary intake, lifestyle and biochemical factors on metabolic health in obese adolescents.

BACKGROUND AND AIMS: Obesity devoid of metabolic abnormalities is known as metabolically healthy obesity (MHO). The aim of the study was to examine determinants of MHO during adolescence. METHODS AND RESULTS: From among 710 obese adolescents, 43 girls and 57 boys were classified as metabolically unhealthy (abdominal obesity and ≥2 risk components of metabolic syndrome). MHO (absence of any cardiometabolic risk factor) was found in 211 girls and 131 boys (regardless of waist circumference) and in 33 girls and 27 boys (without abdominal obesity). Laboratory and anthropometric parameters, dietary records and various lifestyle factors were compared between MHO vs. those unhealthy. The prevalence of MHO regardless of waist circumference was higher in girls than in boys (53.1 vs. 41.9%) but comparable when abdominal obesity was excluded (8.3 vs. 8.6%). Anthropometric variables, levels of gamma-glutamyl transferase, total and low-density lipoprotein cholesterol in both genders, hs-C-reactive protein in girls and alanine aminotransferase in boys differentiated the two metabolic phenotypes. Uric acid was related to metabolic health only in the analysis of MHO without abdominal obesity. Total hours of sleep, bedtime, time of the last daily meal, regular meal consumption and protein intake in boys and screen time, the score of disinhibition and diet composition in girls were found to impact cardiometabolic health. CONCLUSIONS: In obese adolescents, metabolic health was related to anthropometric and biochemical parameters and only weak associations were found with most of the lifestyle factors studied. Uric acid concentration associated with metabolic health when abdominal obesity was excluded.

Metabolically healthy obese individuals -- mechanisms and clinical relevance.

Obesity is associated with an increased risk of premature death and represents a fast growing worldwide health problem. Although it has been long recognized that obesity is associated with an impaired insulin sensitivity, significantly increases the risk of developing type 2 diabetes, dyslipidemia, fatty liver disease, hypertension, cardiovascular disease and certain types of cancers, a subgroup of obese individuals called metabolic healthy obese seems to be protected from metabolic and cardiovascular obesity comorbidities. This article focuses on potential mechanisms underlying the healthy obese phenotype (protection against development of hepatic steatosis, inflammation of visceral adipose tissue, ectopic fat deposition and adipose tissue dysfunction) and on clinical relevance of this interesting subgroup of obese individuals. Additionally, definition, epidemiology and stability of healthy obese phenotype are discussed.

Obesity and infection: reciprocal causality.

Associations between different infectious agents and obesity have been reported in humans for over thirty years. In many cases, as in nosocomial infections, this relationship reflects the greater susceptibility of obese individuals to infection due to impaired immunity. In such cases, the infection is not related to obesity as a causal factor but represents a complication of obesity. In contrast, several infections have been suggested as potential causal factors in human obesity. However, evidence of a causal linkage to human obesity has only been provided for adenovirus 36 (Adv36). This virus activates lipogenic and proinflammatory pathways in adipose tissue, improves insulin sensitivity, lipid profile and hepatic steatosis. The E4orf1 gene of Adv36 exerts insulin senzitizing effects, but is devoid of its pro-inflammatory modalities. The development of a vaccine to prevent Adv36-induced obesity or the use of E4orf1 as a ligand for novel antidiabetic drugs could open new horizons in the prophylaxis and treatment of obesity and diabetes. More experimental and clinical studies are needed to elucidate the mutual relations between infection and obesity, identify additional infectious agents causing human obesity, as well as define the conditions that predispose obese individuals to specific infections.

Fatty acid composition of adipose tissue triglycerides in obese diabetic women after bariatric surgery: a 2-year follow up.

Bariatric surgery is the most effective method in the treatment of obesity and type 2 diabetes (T2DM). The aim of this study was to evaluate the effects of different types of bariatric procedures on remission of T2DM and on the fatty acid composition in subcutaneous adipose tissue. Patients included obese diabetic women who underwent bariatric surgery: biliopancreatic diversion (BPD), n=8, laparoscopic gastric banding (LAGB), n=9 or laparoscopic greater curvature plication (LGCP), n=12. Anthropometric characteristics and fatty acid composition of adipose tissue (FA AT) were analyzed before surgery, then 6 months and 2 years after surgery. FA AT was analyzed by gas chromatography. Diabetes remission was estimated. BPD was most efficient in inducing a remission of diabetes (p=0.004). Significantly higher increases in lauric (12:0), myristoleic (14:1n-5) and palmitoleic (16:1n-7) acids and delta-9 desaturase were found two years after BPD, suggesting higher lipogenesis in adipose tissue. Docosatetraenoic acid (22:4n-6) increased significantly after BPD, while docosapentaenoic acid (22:5n-3) decreased 6 months after BPD and increased after 2 years. No changes were found after LAGB and LGCP after 2 years. Bariatric surgery led to significant changes in the fatty acid composition of subcutaneous adipose tissue in severely obese diabetic women after six months and two years, and was partly influenced by the type of surgery used.

Association of plasma lipids fatty acid composition with metabolic profile of Czech adolescents.

Obesity in childhood increases the risk of obesity in adulthood and is predictive for the development of metabolic disorders. The fatty acid composition is associated with obesity and obesity-associated disorders. We investigated the relationship between serum fatty acids composition, adiposity, lipids profile, parameters of glucose metabolism and leptin. The study subjects were 380 adolescents aged 15.0-17.9 years. The study's variables included anthropometric measurements, levels of serum lipids and hormonal parameters. Individual fatty acids were determined in plasma by gas-liquid chromatography. Palmitoleic acid (16:1n-7, PA) significantly positively correlated with percentage of body fat. Saturated fatty acids in phospholipids (PL) positively correlated with BMI and percentage of body fat. PA content in all lipids classes positively correlated with total cholesterol (TC), HDL cholesterol, triglycerides (TG) levels. Stearoyl-CoA desaturase (SCD) activity positively correlated with percentage of body fat and positive correlations of SCD and PA level with leptin were found. Plasma PA content and SCD are associated with adiposity and leptin in obese adolescents. No significant correlation between PA level and insulin resistance was found. Palmitoleate positively correlated with TC, HDL cholesterol, TG and LDL cholesterol levels.

Fat mass and obesity associated gene variants are associated with increased growth hormone levels and affect glucose and lipid metabolism in lean women.

First intron variability of the fat mass and obesity associated gene (FTO) has strong impact on adiposity. We focused on lean women carrying the most "obesity-risk" haplotype to study their anthropometric parameters and hormonal and metabolic profile. Genotype-phenotype correlation was performed in a group of 172 lean women (body mass index (BMI) >/=18.5 and 25 kg/m(2); age 26.8+/-7.26 years), 77 of them used hormonal contraceptives. Even in lean women the association of the risk haplotype CAGA with BMI was confirmed but it did not influence the anthropometric indices of body composition. CAGA carriers compared to non-carriers had significantly higher both fasting (p=0.016) and post glucose load (p<0.001) levels of growth hormone (GH), significantly higher glucose, insulin and C-peptide levels in the late phase of oGTT and lower fasting concentration of total cholesterol and LDL-cholesterol. Administration of hormonal contraceptives further increased observed hormonal and metabolic effects in CAGA carriers. We conclude that higher levels of GH in lean women carrying the FTO "obesity risk" haplotype could protect them from the development of obesity. The relation between the FTO gene variability and GH secretion has to be elucidated. This is the first study demonstrating the interaction of FTO genotype with hormonal contraception.

Association of adenovirus 36 infection with obesity-related gene variants in adolescents.

Both, common gene variants and human adenovirus 36 (Adv36) are involved in the pathogenesis of obesity. The potential relationship between these two pathogenic factors has not yet been investigated. The aim of our study was to examine the association of obesity susceptibility loci with Adv36 status. Genotyping of ten gene variants (in/near TMEM18, SH2B1, KCTD15, PCSK1, BDNF, SEC16B, MC4R, FTO) and analysis of Adv36 antibodies was performed in 1,027 Czech adolescents aged 13.0-17.9 years. Variants of two genes (PCSK1 and BDNF) were associated with Adv36 seropositivity. A higher prevalence of Adv36 antibody positivity was observed in obesity risk allele carriers of PCSK1 rs6232, rs6235 and BDNF rs4923461 vs. non-carriers (chi(2)=6.59, p=0.010; chi(2)=7.56, p=0.023 and chi(2)=6.84, p=0.033, respectively). The increased risk of Adv36 positivity was also found in PCSK1 variants: rs6232 (OR=1.67, 95 % CI 1.11-2.49, p=0.016) and rs6235 (OR=1.34, 95 % CI 1.08-1.67, p=0.010). PCSK1 rs6232 and BDNF rs925946 variants were closely associated with Adv36 status in boys and girls, respectively (chi(2)=5.09, p=0.024; chi(2)=7.29, p=0.026). Furthermore, PCSK1 rs6235 risk allele was related to Adv36 seropositivity (chi(2)=6.85, p=0.033) in overweight/obese subgroup. In conclusion, our results suggest that obesity risk variants of PCSK1 and BDNF genes may be related to Adv36 infection.

Adenovirus 36 infection: a role in dietary intake and response to inpatient weight management in obese girls.

Human adenovirus 36 (Adv36) increases adiposity and is more prevalent in overweight and obese children. Dietary intake in animal models is comparable regardless of Adv36 status. The effects of Adv36 on obesity treatment outcomes have not been clarified. The aim of this study is to investigate the pre-treatment dietary intake and the response to a 4-week inpatient weight management in 184 obese adolescent girls aged 13.0-17.9 years with respect to the presence of Adv36 antibodies. Evaluation of 3-day dietary records did not show any difference in daily intake of energy and essential nutrients between Adv36 antibody positive and negative girls. After the intervention Adv36 positive girls presented with significantly greater decrease of waist circumference (P=0.020), z-score of waist circumference (P=0.024), waist-to-hip ratio (P=0.007) and weight-to-height ratio (P=0.019) compared with Adv36 negative girls. On the contrary, the sum of four skinfolds decreased significantly more in Adv36 negative than in Adv36 positive individuals (P=0.013). Neither body fat percentage nor metabolic and hormonal parameters showed any significant relevance to Adv36 status in response to weight loss intervention. In conclusion, energy restriction in Adv36 antibody positive girls was associated with greater decrease of abdominal obesity and preservation of subcutaneous fat tissue than in those antibody negative.

Clinical and laboratory characteristics of 1179 Czech adolescents evaluated for antibodies to human adenovirus 36.

BACKGROUND: Human adenovirus 36 (Adv36) is associated with obesity in children. Most prior studies have been small and the association of Adv36 status with markers of metabolic risks has been inconsistent. OBJECTIVES: To determine the prevalence of Adv36 antibodies in different weight categories of adolescents and to evaluate the association of Adv36 infection with anthropometric parameters and cardiometabolic health risks. SUBJECTS AND METHODS: In 1179 Czech adolescents (85 underweight, 506 normal weight, 160 overweight and 428 obese), the following variables were evaluated: anthropometric (body weight, height, body mass index, circumferences, fat mass), blood pressure, biochemical and hormonal (lipid profile, glucose, insulin, liver enzymes, adiponectin) and Adv36 antibodies (enzyme-linked immunosorbent assay). RESULTS: Of the total cohort, 26.5% were positive for Adv36 antibodies (underweight: 22.3%; normal weight: 21.5%; overweight: 40.0% and obese: 28.0%). The odds ratio for Adv36 antibody positivity evaluated vs normal weight was 2.61 for overweight (95% confidence interval (CI): 1.77-3.86, P<0.001) and 1.46 for obesity (95% CI: 1.07-1.99, P=0.016). A significantly higher prevalence of Adv36 infection was observed in female subjects (32.5%) in comparison to male subjects (19.7%; P<0.001). Adv36 positivity of the whole cohort was significantly related to body weight (P=0.042), body mass index (P=0.015), hip circumference (P=0.004), body height z-score (P=0.029), and total body fat (P=0.000) and trunk fat (P=0.000). Adv36 antibody-positive girls demonstrated significantly higher body height (167.8 vs 165.0 cm, P=0.01) and waist circumference (77.0 vs 72.0 cm, P=0.01). Infected adolescents exhibited significantly higher levels of total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-C), but lower levels of blood glucose. Liver enzymes were significantly increased only in Adv36-positive boys. CONCLUSION: These results demonstrated an association of Adv36 antibodies with obesity and an even greater association with overweight. Adv36 positivity was related to increased fat mass, levels of TC and LDL-C, but to decreased level of blood glucose. No relation to adiponectin levels was revealed.

Association of obesity susceptibility gene variants with metabolic syndrome and related traits in 1,443 Czech adolescents.

Genome-wide association studies have revealed several gene variants associated with obesity; however, only a few studies have further investigated their association with metabolic syndrome. We performed a study of eleven variants in/near genes TMEM18, SH2B1, KCTD15, PCSK1, BDNF, SEC16B, MC4R, and FTO in Czech adolescents and analysed their association with obesity, metabolic syndrome and related traits. Genotyping was performed in 1,443 adolescents aged 13.0-17.9 years. Anthropometric parameters, biochemical parameters and blood pressure were assessed. Metabolic syndrome was defined according to the International Diabetes Federation. The FTO rs9939609 variant was associated with overweight/obesity (OR 1.40, 95% CI 1.21-1.63, P < 0.001). The minor allele of TMEM18 rs7561317 was related to underweight (OR 1.78, 95% CI 1.14-2.79, P = 0.015). BDNF rs925946 and MC4R rs17782313 were associated with metabolic syndrome (OR 1.53, 95% CI 1.14-2.04, P = 0.005; 1.51, 95% CI 1.12-2.04, P = 0.009). The PCSK1 rs6235 variant was negatively related to increased blood glucose (OR 0.69, 95% CI 0.49-0.97, P = 0.040). In conclusion, the FTO variant was associated with overweight/obesity in Czech adolescents. Moreover, MC4R and BDNF variants increased the risk of metabolic syndrome, probably through their effect on abdominal obesity. The PCSK1 variant may have a protective role in the development of type 2 diabetes.

Role of the PPARalpha Leu162Val and PPARgamma2 Pro12Ala gene polymorphisms in weight change after 2.5-year follow-up in Czech obese women.

The aim of this study was to investigate the possible effect of PPARalpha and PPARgamma2 variants on weight and eating attitudes as well as on their changes after 2.5-year follow-up. The study was carried out in 246 Czech non-diabetic obese women (age 49.0 +/- 11.9 years; BMI 38.1 +/- 7.0 kg/m(2)). The comprehensive weight management programme included lowenergy diet, increased physical activity and lifestyle modification. Anthropometric parameters (body weight and height, waist and hip circumferences) and body composition were measured. The Three-Factor Eating Questionnaire and Beck Depression Inventory were evaluated. At baseline and after the follow-up period, fasting levels of serum glucose, plasma adiponectin, ghrelin, leptin, and lipid profile were determined. The dependence of monitored parameters on the Pro12Ala in PPARgamma2 and Leu162Val in PPARalpha and stage of the treatment (baseline; 2.5- year follow-up) was evaluated using the repeated measures ANOVA model. The cohort was re-examined after 2.5 years, independent of regular checkups and adherence to lifestyle recommendation. Significant favourable changes in anthropometric indexes, lipid profile, leptin, ghrelin and adiponectin levels as well as in dietary restraint and hunger scores were revealed at 2.5-year check-up. However, no changes in the scores of disinhibition and depression were demonstrated. Despite several observed significant differences between carriers and non-carriers of the minor alleles at baseline and at the follow-up, the repeated measures ANOVA did not reveal any significant effect of the PPARalpha and PPARgamma2 polymorphisms on anthropometric, biochemical, hormonal and psycho-behavioural characteristics, neither at baseline nor at the 2.5-year follow-up.

[Neuropeptide Y, ghrelin and leptin plasma levels in anorexia nervosa patients and their changes during six-week refeeding]. / Plazmatické hladiny neuropeptidu Y, ghrelinu a leptinu a pacientek s anorexia nervosa a jejich zmeny po sestitýdenní realimentaci.

OBJECTIVE: Anorexia nervosa (AN) is characterized by markedly changes in hormone secretion influencing food intake, energy homeostasis and long-term body weight regulation. The aim of this study was to determine neuropeptide Y (NPY), ghrelin and leptin plasma levels and their changes after six weeks of nutritional-rehabilitation program in severely malnourished anorexia nervosa patients. METHODS: Ten women with DSM-IV diagnosed anorexia nervosa, hospitalized (BMI 14.74 +/- 0.43; age 23.3 +/- 1.0) and ten age-matched healthy women (BMI 21.45 +/- 0.72; age 24.3 +/- 0.8) were enrolled to the study. Fasting plasma levels of NPY, ghrelin and leptin were measured before and after the treatment. RESULTS: Fasting plasma ghrelin and NPY levels were significantly increased in AN patients comparing to healthy women, while plasma leptin was decreased. After six weeks of the treatment plasma ghrelin levels significantly decreased and plasma leptin levels increased. Plasma NPY levels didn't change during the treatment, average BMI significantly increased in AN patients. CONCLUSIONS: We confirmed that ghrelin and leptin plasma levels express actual nutritional status of a body and did change during the six-weeks refeeding in AN patients. Plasma leptin levels together with constantly increased NPY levels indicate to persisting dysregulation of appetite and body weight control mechanisms in AN patients.

[The first Obesity Unit in Czechoslovakia was established twenty years ago]. / Dvacet let od zalození první Obezitologické jednotky v Ceskoslovensku.

The first Obesity Unit in former Czechoslovakia was established at the Fourth Department of Internal Medicine of the Faculty of General Medicine and Faculty Hospital I twenty years ago. Both personal resources (physicians specialized in metabolism and obesity, psychologist, dietician, physiatrist and medical nurses trained in the care of obese patients) and diagnostic tools (body composition assessment by hydrodensitometry, determination of energy expenditure by indirect calorimetry, evaluation of energy and nutrient intake by PC assessment of dietary records, hormonal and biochemical examinations etc.) enabled comprehensive examinations of obese patients. Obesity unit included a specialized in-patient department where the patients with severe and complicated obesity underwent a comprehensive treatment programme which consisted of very low energy diet developed in collaboration with the Obesity Unit. The article summarizes not only clinical experiences of the unit but also its engagement in education on obesity, in research projects and international collaboration over the past 20-years period. Obesity unit succeeded to keep its continuity in spite of repeated moving between 1997-2002. Since 2002 Obesity Unit has been a part of the Institute of Endocrinology which provided additional modern facilities for hormonal and molecular genetic examinations.