propylthiouracil and Obesity

Taste sensitivity to the bitter compound 6-n-propylthiouracil (PROP) is considered a marker for individual differences in taste perception that may influence food preferences and eating behavior, and thereby energy metabolism. This review describes genetic factors that may contribute to PROP sensitivity including: (1) the variants of the TAS2R38 bitter receptor with their different affinities for the stimulus; (2) the gene that controls the gustin protein that acts as a salivary trophic factor for fungiform taste papillae; and (3) other specific salivary proteins that could be involved in facilitating the binding of the PROP molecule with its receptor. In addition, we speculate on the influence of taste sensitivity on energy metabolism, possibly via modulation of the endocannabinoid system, and its possible role in regulating body composition homeostasis.

Topics: Body Composition; Body Mass Index; Diet; Energy Metabolism; Feeding Behavior; Food Preferences; Humans; Obesity; Propylthiouracil; Receptors, Cannabinoid; Taste Buds; Taste Perception; Taste Threshold

Taste plays an important role in processes such as food choices, nutrition status and health. Salivary proteins contribute to taste sensitivity. Taste reduction has been associated with obesity. Gender influences the obesity predisposition and the genetic ability to perceive the bitterness of 6-

Topics: Adult; Aged; Body Mass Index; Female; Genotype; Humans; Male; Middle Aged; Obesity; Propylthiouracil; Salivary Proteins and Peptides; Taste; Young Adult

In this manuscript, we present the protocol for a study that applies incentive sensitization theory to improve vegetable intake in overweight and obese adults. This 8-week, randomized, controlled, community-based feeding study with an 8-week follow-up seeks to use repeated exposure to amounts of vegetables recommended by federal guidance to increase the primary outcome of the relative reinforcing value of vegetables compared to a snack food. A community-based design is used to give participants autonomy in choosing their method of exposure. Secondary outcomes include: 1) Determine potential moderators of incentive sensitization of vegetables, including genetic polymorphisms associated with food reinforcement and obesity, 6-n-propylthiouracil tasting status, and delay discounting. 2) Determine whether adding vegetables to the diet results in participants substituting low-energy-dense vegetables for energy-dense foods or whether energy-dense food consumption is independent of vegetable consumption. 3) Determine whether reductions in adiposity are associated with substitution of vegetables in the diet. 4) Determine if markers of bone turnover change. 5) Assess changes in self-reported secondary outcomes measured by questionnaire such as self-efficacy to eat vegetables. The results of this study will provide information about the drivers of individual choice to consume recommended amounts of vegetables. The understanding gained will help increase the effectiveness and sustainability of behavior-based interventions focused on improving vegetable intake. This information may also be used to assist in setting dietary guidance targets for the amounts and types of vegetables Americans can, and should, consume.

Topics: Adiposity; Bone Remodeling; Community-Based Participatory Research; Diet; Feeding Behavior; Food Preferences; Humans; Motivation; Obesity; Overweight; Polymorphism, Single Nucleotide; Propylthiouracil; Reinforcement, Psychology; Research Design; Self Efficacy; Social Support; Vegetables

Taste blindness to the bitterness of PROP (6-n-propylthiouracil) has been used as a genetic marker for food selection and adiposity. We have shown that PROP non-taster (NT) women have higher BMIs and habitually consume more fat and energy than either medium-taster (MT) or super-taster (ST) women. These data imply that differences in dietary selection underlie the body weight differences among PROP taster groups. However, no studies investigated energy compensation in women classified by PROP status. We investigated if NTs would compensate less accurately for the calories and fat in a high-fat soup preload in a subsequent test meal compared to MTs and STs. Energy intake from a buffet meal was measured in 75 healthy non-diet-restrained, lean women 30 min after the ingestion of a high-fat soup preload (0.8 kcal/g; 55% calories from fat), calculated to represent 10% of resting energy expenditure for each subject, or the same volume of water. Subjects (n = 20-28/taster group) ate a standard breakfast followed 3 hr later by an ad-libitum buffet lunch, on two occasions. There were no differences in energy intake or macronutrient selection across taster groups after water. After soup, NTs consumed more energy than STs. Fat intake (as %-energy) was higher in NTs (46.4% ± 2.4) compared to either MTs (36.1 ± 1.9%) or STs (38.1% ± 2.3; p < 0.05). NTs overate by 11% ± 5 after the soup compared to MTs and STs who underrate by 16% ± 6 and 26% ± 10, respectively (p < 0.01). These data suggest that small discrepancies in short-term energy compensation and selection of fat after a mixed-nutrient, high-fat preload may play a role in positive energy balance and increased adiposity in women with the PROP non-taster phenotype.

Topics: Adiposity; Adult; Diet; Dietary Fats; Eating; Energy Intake; Feeding Behavior; Female; Food Preferences; Humans; Hyperphagia; Meals; Obesity; Propylthiouracil; Taste; Taste Perception; Water; Young Adult

Little is known as to how 6-n-propylthiouracil (PROP) taster status may influence changes in dietary intake in adults participating in a lifestyle intervention to assist with reducing weight. This secondary data analysis examined changes in energy, percent energy from macronutrients, and food group intake; physical activity; and body mass index (BMI) in super-tasters and non-tasters participating in two randomized controlled trials implementing a lifestyle obesity intervention. One trial focused on lowering energy density of the diet and the other trial focused on changing eating frequency. Overweight and obese participants (n = 57) who completed measures of dietary intake, physical activity, and anthropometrics at 0 and 3 months were included in the analyses. Taster status was determined at baseline: 46 non-tasters and 11 super-tasters. After controlling for condition assignment and baseline values, results indicated that a significantly greater reduction in energy intake occurred for super-tasters as compared to non-tasters (-1149 ± 561 kcal/day vs. -902 ± 660 kcal/day, p < 0.05). No other significant differences in changes in dietary intake, physical activity, or BMI were found. These results suggest that in situations of reducing energy intake, overweight and obese super-tasters may be more successful than overweight and obese non-tasters. More research is needed to understand the influence of taster-status on dietary change during a lifestyle intervention and how this may impact weight loss.

Topics: Adult; Aged; Antimetabolites; Body Mass Index; Diet, Reducing; Eating; Energy Intake; Exercise; Female; Food Preferences; Humans; Male; Middle Aged; Obesity; Overweight; Propylthiouracil; Taste; Taste Threshold; Weight Reduction Programs; Young Adult

Differences in taste perception have been related to eating behavior, nutritional status, and diseases. Recently, taste receptors have been identified in several extra-oral tissues, such as the gastrointestinal tract, where they seem to influence processes like digestion, sense of satiety as well as energy balance and intraluminal changes occurring in obesity. Our study aims to analyze differences in taste perception among 42 obese patients (OB) and 41 normal-weight subjects (LEAN). Polymorphisms in the gene codifying for the bitter taste receptor TAS2R38 and its expression on the surface of the gastric mucosa were tested and compared among OB and LEAN. Taste intensity of PROP (6-n-propylthiouracil), quinine, sucrose, citric acid and NaCl were measured on a labeled magnitude scale. DNA from peripheral whole blood was extracted and three polymorphisms in the TAS2R38 gene (rs713598, rs1726866, rs10246939) analyzed. Gastric biopsies were collected during bariatric surgery in OB and during endoscopy in LEAN. RNA was extracted and TAS2R38 gene expression assessed by RT-Real-Time qPCR. Anamnestic and anthropometric data were recorded in all participants during baseline visits. Logistic regression analysis showed that OB perceives sweet (sucrose) and bitter (PROP or 6-n-propylthiouracil) taste more intensely than LEAN (p-value = 0.02 and p-value = 0.005, respectively). While polymorphisms in TAS2R38 gene did not differ among OB and LEAN, we observed a significant increase of TAS2R38 mRNA levels in the stomach of OB compared to LEAN (p = 0.01). Our results provide new evidence of a link between obesity and altered taste perception as well as TAS2R38 expression in the stomach.

Topics: Humans; Obesity; Propylthiouracil; Receptors, G-Protein-Coupled; Stomach; Taste; Taste Perception

Obesity leads to multiple health problems, including diabetes, fatty liver, and even cancer. Here, we report that urolithin A (UA), a gut-microflora-derived metabolite of pomegranate ellagitannins (ETs), prevents diet-induced obesity and metabolic dysfunctions in mice without causing adverse effects. UA treatment increases energy expenditure (EE) by enhancing thermogenesis in brown adipose tissue (BAT) and inducing browning of white adipose tissue (WAT). Mechanistically, UA-mediated increased thermogenesis is caused by an elevation of triiodothyronine (T3) levels in BAT and inguinal fat depots. This is also confirmed in UA-treated white and brown adipocytes. Consistent with this mechanism, UA loses its beneficial effects on activation of BAT, browning of white fat, body weight control, and glucose homeostasis when thyroid hormone (TH) production is blocked by its inhibitor, propylthiouracil (PTU). Conversely, administration of exogenous tetraiodothyronine (T4) to PTU-treated mice restores UA-induced activation of BAT and browning of white fat and its preventive role on high-fat diet (HFD)-induced weight gain. Together, these results suggest that UA is a potent antiobesity agent with potential for human clinical applications.

Topics: Adipocytes, Brown; Adipocytes, White; Adipose Tissue, Brown; Adipose Tissue, White; Animals; Anti-Obesity Agents; Coumarins; Diet, High-Fat; Energy Metabolism; Fatty Liver; Glucose Intolerance; Insulin Resistance; Maillard Reaction; Male; Mice; Mice, Inbred C57BL; Mice, Obese; Obesity; Propylthiouracil; Thermogenesis; Triiodothyronine; Weight Gain

Balanced coagonists of glucagon-like peptide-1 (GLP-1) and glucagon receptors are emerging therapies for the treatment of obesity and diabetes. Such coagonists also regulate lipid metabolism, independent of their body weight lowering effects. Many actions of the coagonists are partly mediated by fibroblast growth factor 21 (FGF21) signaling, with the major exception of bile homeostasis. Since thyroid hormone is an important regulator of bile homeostasis, we studied the involvement of thyroid hormone in coagonist-induced changes in lipid and bile metabolism.. We evaluated the effect of a single dose of coagonist Aib2 C24 chimera2 at 150 to 10000 µg/kg on tetraiodothyronine (T4) and triiodothyronine (T3) in high-fat diet-induced obese (DIO) mice and chow-fed mice. Repeated dose treatment of coagonist (150 µg/kg, subcutaneously) was assessed in four mice models namely, on lipid and bile homeostasis in DIO mice, propylthiouracil (PTU)-treated DIO mice, methimazole (MTM)-treated DIO mice and choline-deficient, L-amino acid-defined, highfat diet (CDAHFD)-induced nonalcoholic steatohepatitis (NASH).. Single dose treatment of coagonist did not alter serum T3 and T4 in chow-fed mice and DIO mice. Coagonist treatment improved lipid metabolism and biliary cholesterol excretion. Chronic treatment of GLP-1 and glucagon coagonist did not alter serum T3 in hypothyroid DIO mice and CDAHFDinduced NASH. Coagonist increased serum T4 in DIO mice after 4 and 40 weeks of treatment, though no change in T4 levels was observed in hypothyroid mice or mice with NASH.. Our data demonstrate that coagonist of GLP-1 and glucagon receptors does not modulate bile homeostasis via thyroid signaling.

Topics: Animals; Bile; Diet, High-Fat; Glucagon-Like Peptide 1; Liver; Male; Methimazole; Mice; Mice, Inbred C57BL; Non-alcoholic Fatty Liver Disease; Obesity; Propylthiouracil; Receptors, Glucagon; Thyroxine; Triglycerides; Triiodothyronine

We assessed orosensory detection of a long-chain fatty acid, linoleic acid (LA), and a bitter taste marker, 6-n-propylthiouracil (PROP), and correlated lipid-taster subjects with PROP detection and polymorphism in genes encoding bitter and lipid taste receptors, respectively, TAS2R38 and CD36, in normal weight and obese subjects.. The normal weight (n = 52, age = 35.3 ± 4.10 years, BMI = 23.22 ± 1.44 kg/m. The study included the participants who could detect LA, i.e., lipid-tasters. There was a positive correlation between BMI and detection thresholds for fat and bitter taste in normal weight and obese subjects. Obese participants showed a positive correlation between LA and PROP detection thresholds. PROP detection thresholds were higher for CD36 SNP (rs1761667) and TAS2R38 SNPs (rs1726866 and rs10246939) in obese participants compared to normal weight subjects. LA detection thresholds were not high for CD36 SNP (rs1761667) or TAS2R38 SNP (rs1726866 and rs10246939) in obese participants.. Orosensory detection thresholds for fat and bitter taste are associated with BMI, and CD36 and TAS2R38 genotypes are not always associated with taste phenotypes.

Topics: Adult; Body Weight; Case-Control Studies; CD36 Antigens; Humans; Male; Obesity; Polymorphism, Single Nucleotide; Propylthiouracil; Receptors, G-Protein-Coupled; Taste

Topics: Adolescent; Adult; Body Mass Index; Coffee; Female; Food Preferences; Fruit and Vegetable Juices; Humans; Ilex paraguariensis; Male; Middle Aged; Obesity; Philosophy; Propylthiouracil; Reaction Time; Taste; Taste Perception; Time Factors; Young Adult

Reduced taste sensitivity to 6-n-propylthiouracil (PROP), a genetic trait regarded as a general index for oral chemosensory perception, has been associated with a calorie-rich food preference and lower circulating endocannabinoid levels in participants with normal weight (NW), which suggests an adaptive mechanism to maintain a lean phenotype. In this study, we assessed whether participants with obesity (OB) show different patterns of plasma endocannabinoids and lipid metabolism biomarkers from those of NW, with further categorization based on their PROP sensitivity. NW and OB were classified by their PROP taster status as non-tasters (NT), medium-tasters (MT) and supertasters (ST). The blood samples were analysed for plasma endocannabinoids, nonesterified fatty acids (NEFA) and retinol, which have been associated to metabolic syndrome. In OB, we found a higher BMI and lower circulating endocannabinoids in ST vs. OB NT. However, OB ST showed lower circulating NEFA and retinol levels, which suggested a more favourable lipid metabolism and body fat distribution than those of OB NT. We confirmed lower plasma endocannabinoid levels in NW NT than in NW ST. These data suggest that PROP taste sensitivity determines metabolic changes and ultimately body mass composition differently in OB and NW.

Topics: Adult; Body Mass Index; Body Weight; Endocannabinoids; Erythrocytes; Female; Humans; Lipid Metabolism; Male; Middle Aged; Obesity; Propylthiouracil; Taste

Eating behaviors and obesity are complex phenotypes influenced by genes and the environment, but few studies have investigated the interaction of these two variables. The purpose of this study was to use a gene-environment interaction model to test for differences in children's food acceptance and body weights.. Inherited ability to taste 6-n-propylthiouracil (PROP) was assessed as a marker of oral taste responsiveness. Food environment was classified as "healthy" or "unhealthy" based on proximity to outlets that sell fruits/vegetables and fast foods using Geographic Information Systems (GIS). The cohort consisted of 120 children, ages 4-6 years, recruited from New York City over 2005-2010. Home address and other demographic variables were reported by parents and PROP status, food acceptance, and anthropometrics were assessed in the laboratory. Based on a screening test, children were classified as PROP tasters or non-tasters. Hierarchical linear models analysis of variance was performed to examine differences in food acceptance and body mass index (BMI) z-scores as a function of PROP status, the food environment ("healthy" vs. "unhealthy"), and their interaction.. Results showed an interaction between taster status and the food environment on BMI z-score and food acceptance. Non-taster children living in healthy food environments had greater acceptance of vegetables than taster children living in healthy food environments (P ≤ 0.005). Moreover, non-tasters from unhealthy food environments had higher BMI z-scores than all other groups (P ≤ 0.005). Incorporating genetic markers of taste into studies that assess the built environment may improve the ability of these measures to predict risk for obesity and eating behaviors.

Topics: Body Mass Index; Body Weight; Child; Child, Preschool; Cohort Studies; Consumer Behavior; Cross-Sectional Studies; Fast Foods; Female; Food Preferences; Food, Organic; Fruit; Gene-Environment Interaction; Genetic Markers; Geographic Information Systems; Humans; Male; New York City; Obesity; Phenotype; Propylthiouracil; Residence Characteristics; Socioeconomic Factors; Taste; Vegetables

Previous studies have shown that inherited taste blindness to bitter compounds like 6-n-propylthiouracil (PROP) may be a risk factor for obesity, but this literature has been highly controversial. The objectives of this study were (i) to confirm findings that show an interaction between PROP status and sex on BMI z-score, and (ii) to determine if sex also interacts with variations in TAS2R38 (phenylthiocarbamide (PTC) genotype) to influence weight status in 4-6 year olds. Also, we tested whether nontaster children consumed more fat and total energy at laboratory-based meals. Seventy-two ethnically diverse children who ranged in weight status were classified as tasters (N = 52) or nontasters (N = 20) using a standard PROP screening solution. Anthropometric measures were taken, and at the end of each visit, children ate ad libitum from test meals intended for exploratory purposes. Genomic DNA was extracted from saliva and alleles at TAS2R38 were genotyped for A49P polymorphisms. In 75.8% of children, PTC genotype predicted PROP phenotype, whereas in 24.4%, genotype did not predict phenotype. PROP nontaster males had higher BMI z-scores than taster-males and females in both groups (P < 0.05), but due to a three-way interaction between PROP phenotype, TAS2R38 genotype, and sex, this relationship was only true for children who were homozygous for the bitter-insensitive allele (P < 0.0005). There were no differences in test-meal intake as a function of PROP phenotype or TAS2R38 genotype. These results suggest that the TAS2R38 variation, PROP phenotype, and sex interact to impact obesity risk in children. Future studies should be done to determine how this trait influences energy balance.

Topics: Body Mass Index; Body Weight; Child; Child, Preschool; Female; Genetic Diseases, Inborn; Genetic Predisposition to Disease; Genetic Variation; Genotype; Humans; Male; Obesity; Propylthiouracil; Receptors, G-Protein-Coupled; Risk; Sex Characteristics; Taste; Taste Disorders; Thiourea

To examine the relationship of 6-n-propylthiouracil (PROP) sensitivity to BMI while statistically controlling for demographic characteristics in two age groups of children: 9-10 years and 17-18 years (n 1551).. Cross-sectional design with a multi-ethnic (White, African-American, Hispanic, Other) sample of 813 children aged 9-10 years and 738 children aged 17-18 years. Children were recruited from local elementary and high schools with at least 30 % minority ethnic enrolment. Children's height, weight and waist circumference were measured along with their PROP taster status. PROP was measured using two paper discs, one impregnated with NaCl (1.0 mol/l) and the other with PROP solution (0.50 mmol/l).. A significant PROP sensitivity by socio-economic status (SES) interaction term (P = 0.010) was detected wherein supertasters had the largest BMI percentile and Z-score, but only among the group with highest SES.. The results suggest that other factors overwhelmed the influence of PROP sensitivity on adiposity in lower-SES groups. The percentage of variance accounted for by the interaction term was about 1 %. Thus, PROP supertasters had the largest BMI percentile and Z-score, but only among the highest-SES group.

Topics: Adolescent; Analysis of Variance; Body Mass Index; Child; Cross-Sectional Studies; Ethnicity; Female; Humans; Income; Male; Obesity; Propylthiouracil; Social Class; Taste

Topics: Adult; Body Mass Index; Genotype; Humans; Obesity; Phenotype; Propylthiouracil; Receptors, G-Protein-Coupled; Taste; Taste Buds

A half-century ago, Fischer and colleagues found correlations between food preference and genetic markers of taste [6-n-propylthiouracil (PROP), quinine]. Recently, a number of studies report differences in sweet liking/disliking with taste phenotype or genotype. Here we modeled optimal liking for milk/sugar mixtures using the response surface method among 79 mostly normal weight adults (36 women) who reported low dietary restraint. Two non-overlapping phenotype analyses were performed: a) discordance in PROP versus quinine bitterness and b) number of fungiform papillae (FP, taste papillae on the tongue tip). Although all phenotype groups liked highly sweet and creamy sensations (in liking by sensation models), the fat and sugar levels for hedonic optima varied (in liking by concentration models). Males generally liked higher fat (20 to 40%) and sugar levels, with females disliking unsweetened cream. In quinine/PROP groups, liking peaked at 30% fat/15% sucrose for men and women who tasted 0.32 mM quinine more bitter than 3.2 mM PROP (n=15); a group previously shown to have highest sugar intakes (Duffy et al., 2003). Those tasting PROP more bitter than quinine (n=14) reported greater creamy/sweet sensations, with peak liking at lower fat and sweet levels (3.3% fat/10% sucrose). Generally, those in the high FP group perceived more creamy/sweet sensations with level of liking more influenced by sugar level, especially among high FP females. At high sugar/high fat levels low FP males and females retained this liking while liking fell off for those in the high FP group. In summary, although most liked sweet/creamy sensations, perceptual differences in these sensations varied with oral phenotype, explaining some of the differences in the amount of sugar and fat required to reach hedonic optima. A high affinity for high sugar/high fat mixtures among oral phenotype subgroups has relevance for energy consumption and could explain the link previously observed between oral sensation and body weight.

Topics: Adult; Analysis of Variance; Carbohydrates; Dose-Response Relationship, Drug; Fats; Feeding Behavior; Female; Food Preferences; Humans; Male; Obesity; Phenotype; Propylthiouracil; Quinine; Sex Factors; Taste; Taste Threshold

Sensitivity to the bitter compound 6-n-propylthiouracil (PROP) is genetically mediated. Sensitivity to PROP has been associated with weight status in both adults and children.. To determine whether there is an association between PROP sensitivity and BMI in low-income children of diverse race/ethnicity, among whom there is a high prevalence of obesity.. Eighty-one preschool-aged children attending Head Start tasted a solution of 560 micromol/l PROP and reported whether it tasted "like water" or "like something else". Mothers reported child's race, age, maternal education, maternal weight and height, child's reluctance to sample new foods via the Food Neophobia Scale (FNS), and child's dietary intake using a food frequency questionnaire. Child weight and height were measured. BMI was calculated and for children, expressed in z-scores. Regression analyses were used to evaluate the relationship between child's PROP taster status and BMI z-score, testing covariates child's age, gender, race, maternal education and BMI, and child's FNS score. Children's dietary intake was compared by PROP taster status.. PROP tasters, compared with nontasters, had significantly higher BMI z-scores (0.99 (s.d. 1.24) vs. 0.03 (1.12), P=0.004) and had a significantly higher prevalence of overweight (31.8% vs. 5.6%, P=0.025), but demonstrated no differences in reported dietary intake. The most parsimonious model predicting the child's BMI z-score included only maternal BMI and the child's PROP taster status (R(2)=22.3%).. A genetically mediated ability to taste bitter may contribute to obesity risk in low-income, preschool-aged children.

Topics: Body Mass Index; Child, Preschool; Diet Records; Female; Food Preferences; Genetic Predisposition to Disease; Humans; Male; Obesity; Poverty; Propylthiouracil; Risk Factors; Socioeconomic Factors; Surveys and Questionnaires; Taste; Vegetables

The obese Zucker rat has alterations in thyroid hormone metabolism resulting in a lower serum T3 concentration and T3 plasma appearance rate compared to its lean littermates. This study was undertaken to measure the contribution of specific nonthyroidal tissues to the total production of T3 in vivo in the Zucker fatty rat. Simultaneous pulse kinetic studies of T4 and T3 were performed in lean and obese Zucker littermates and analyzed according to a three-pool model of distribution and metabolism. The serum concentration and plasma appearance rate of T3 were both decreased in the obese vs. lean Zucker phenotype (P < 0.05) despite an elevated serum concentration and plasma appearance rate for T4. The quantity of T4 within the fast pool (i.e. liver and kidney) available for deiodination was equal for both phenotypes; however, generation of T3 within the fast pool was impaired for the obese compared to the lean group (-25%; P < 0.05). The tissue content of radiolabeled T3 generated within the liver 24 h post injection of T4 for the obese group was 48% lower (P < 0.02) vs. the lean group. A separate group of lean and obese littermates were surgically thyroid-ectomized and replaced with T4 to maintain a euthyroid state. The obese Zucker group had lower serum T3 concentrations and T3 plasma appearance rates compared to similarly treated lean Zucker animals despite similar T4 serum concentrations. Treatment with propylthiouracil produced a decline in serum T3 plasma appearance rate T3 PAR (-55%; P < 0.02) in the T4-replaced lean rat but no alteration in T3 metabolism in the fatty Zucker rat. We conclude that the obese Zucker rat has impaired T3 synthesis in tissues containing Type I 5-deiodinase despite adequate T4 availability as substrate for deiodination to T3.

Topics: Animals; Kinetics; Male; Models, Biological; Obesity; Phenotype; Propylthiouracil; Rats; Rats, Zucker; Thyroidectomy; Thyroxine; Triiodothyronine

To assess the importance of the role of thyroidal iodine in the pathogenesis of thyroiditis in the obese strain (OS) chicken, a model of spontaneous and severe disease, we studied the effect of antithyroid drugs that reduce thyroidal iodine or prevent its metabolism. Reduction of thyroidal iodine was achieved with KClO4, an inhibitor of iodine transport and mononitrotyrosine (MNT), a drug that promotes loss of thyroidal iodine as iodotyrosines. A regimen consisting of KClO4 and MNT administration beginning in ovo and continuing after hatching reduced thyroidal infiltration to 2% of control values and decreased thyroglobulin antibody (TgAb) production for as long as 9 wk. Untreated birds had severe disease by 5 wk of age. The suppression of disease was independent of TSH, not mediated by generalized immunosuppression and reversed by excess dietary iodine. Two drugs that inhibit the metabolism of iodine, propylthiouracil (PTU) and aminotriazole, reduced thyroidal infiltration and TgAb levels, although to a lesser extent. When splenocytes from OS chickens with thyroiditis were transferred to Cornell strain (CS) chickens, a related strain that develops late onset mild disease, only the recipients that were iodine supplemented developed thyroiditis. In conclusion, autoimmune thyroiditis in an animal model can be prevented by reducing thyroidal iodine or its metabolism and optimal effects require intervention at the embryonic stage.

Topics: Amitrole; Animals; Chickens; Immunotherapy, Adoptive; Iodine; Obesity; Perchlorates; Potassium; Potassium Compounds; Propylthiouracil; Thyroid Gland; Thyroiditis, Autoimmune; Thyrotropin; Tyrosine

Circulating levels of insulin, glucagon, thyroid hormones as well as lipid levels were determined in an obese strain of chicken and their lean controls. Hepatic and muscle glycogen and lipids were also measured. Obese birds had higher plasma lipids accompanied by significantly higher insulin and lower glucagon levels compared to lean controls. Hepatic and muscle triglycerides were also higher in obese birds. Plasma T4 level was significantly higher in obese but T3 was not different in the two groups. Results suggest that genetically obese birds have significantly increased insulin/glucagon ratios as previously reported in the PTU induced hypothyroid-obese chicks (Horm. Metab. Res. 12: 51, 1980) and this could have causal relationship to hyperlipidemia and obesity observed in these birds.

Topics: Animals; Chickens; Glucagon; Hyperlipidemias; Hypothyroidism; Insulin; Male; Obesity; Propylthiouracil; Thyroid Hormones

Recent evidence indicates that the paraventricular nucleus of the hypothalamus (PVN) contains both neurons that produce thyrotropic releasing hormone (TRH) and neurons that are destroyed or disconnected by the knife cuts that produce hypothalamic hyperphagia and obesity. This, and other evidence, suggested linkage between thyroid regulation and appetite control. As predicted, hyperthyroidism potentiated and hypothyroidism tempered the weight gains of knife cut rats. However, these effects were due entirely to increased and decreased, respectively, linear growth, not to differences in the degree of obesity. Enhanced linear growth and elevated growth hormone levels are a minor component of the enhanced weight gain of hypothalamically knife cut rats. Most of the weight gain is due to fat deposition. Only the enhanced linear growth and growth hormone aspect appear to possibly be mediated via the thyroid. In addition, obesifying knife cuts did not reduce goiterogenesis in PTU treated rats, as would be expected if the elaboration of TRH were blocked by obesifying knife cuts. Thus, neither TRH nor thyroxine is involved in the etiology of hypothalamic obesity.

Topics: Animals; Body Weight; Brain; Hyperthyroidism; Hypothalamus; Hypothyroidism; Male; Obesity; Paraventricular Hypothalamic Nucleus; Propylthiouracil; Rats

Topics: Animals; Birds; Body Weight; Clomiphene; Endocrine Glands; Feeding Behavior; Male; Obesity; Propylthiouracil; Testosterone; Thyroxine

Topics: Animals; Body Temperature; Cold Temperature; Diet; Fatty Acids, Nonesterified; Female; Half-Life; Hypothalamus; Iodine; Iodine Isotopes; Obesity; Pituitary Gland; Propylthiouracil; Radioimmunoassay; Rats; Thyroid Function Tests; Thyroid Gland; Thyrotropin; Thyrotropin-Releasing Hormone

Topics: Adolescent; Adult; Alopecia; Antithyroid Agents; Fatigue; Female; Goiter; Graves Disease; Humans; Hyperthyroidism; Iodine Isotopes; Menstruation Disturbances; Middle Aged; Obesity; Propylthiouracil; Thyroid Hormones; Thyroxine; Triiodothyronine