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Query: UMLS:C0028754 (obesity)
 124,988 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Obesity and weight loss have been shown to alter thyroid hormone homeostasis in humans. In dogs, obesity is the most common nutritional problem encountered and weight loss is the cornerstone of its treatment. Therefore, it is important to clarify how obesity and weight loss can affect thyroid function test results in that species. The objectives of this study were to compare thyroid function in obese dogs and in lean dogs and to explore the effects of caloric restriction and weight loss on thyroid hormone serum concentrations in obese dogs. In the first experiment, 12 healthy lean beagles and 12 obese beagles were compared. Thyroid function was evaluated by measuring serum concentrations of total thyroxine (TT4), free thyroxine (FT4), total triiodothyronine (TT3), thyrotropin (TSH), and reverse triiodothyronine (rT3) as well as a TSH stimulation test using 75 microg i.v. of recombinant human TSH. In the second experiment, eight obese beagles were fed an energy-restricted diet [average 63% maintenance energy requirement (MER)] until optimal weight was obtained. Blood samples for determination of TT4, FT4, TT3, TSH and rT3, were taken at the start and then weekly during weight loss. Only TT3 and TT4 serum concentrations were significantly higher in obese dogs as compared to lean dogs. In the second experiment, weight loss resulted in a significant decrease in TT3 and TSH serum concentrations. Thus obesity and energy restriction significantly alter thyroid homeostasis in dogs, but the observed changes are unlikely to affect interpretation of thyroid function test results in clinics.
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PMID:Evaluation of thyroid function in obese dogs and in dogs undergoing a weight loss protocol. 1294 59

Spot 14 is a 17-kDa protein expressed in lipogenic tissues and is postulated to play a role in thyroid hormone stimulation of lipogenesis. To further our understanding of Spot 14 regulation in humans, our laboratory recently cloned the human Spot 14 gene. The gene is highly homologous to the rat Spot 14 ortholog and located on a chromosomal region implicated in human obesity. Because our understanding of Spot 14 transcriptional regulation is derived from rat promoter studies, we assessed the thyroid hormone responsivity of the human Spot 14 promoter. These studies revealed a significantly greater thyroid hormone response for the human promoter, compared with the rat. Deletional studies of the human Spot 14 promoter reveal a 774-bp region at approximately position -2700, which is both necessary and sufficient for the thyroid hormone response. EMSAs with subfragments from this region identify a 146-bp DNA fragment capable of binding a TRbeta1-retinoid X receptor heterodimer. Site-directed mutagenesis confirmed the identity of a candidate DR-4 thyroid hormone response element within this fragment that is similar, but not identical, to the two rat Spot 14 thyroid hormone response elements. We hypothesize that the difference in thyroid hormone response between the orthologous promoters may allow a selective advantage to each species based on their different nutritional and physiological niches.
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PMID:Human spot 14 glucose and thyroid hormone response: characterization and thyroid hormone response element identification. 1296 53

The symptoms of severe early-onset obesity, adrenal insufficiency, and red hair define the proopiomelanocortin (POMC) deficiency syndrome as described so far in two children with complete loss-of-function mutations of the human POMC gene. In POMC deficiency, obesity reflects the lack of POMC-derived peptides as ligands at the melanocortin (MC) MC4 and MC3 receptors, which are expressed in the hypothalamic leptin-melanocortin pathway of body weight regulation. Hypocortisolism and alteration of pigmentation are caused by the lack of POMC-derived peptides at the adrenal MC2 receptor and the skin MC1 receptor, respectively. Here we describe three new cases of complete loss-of-function mutations of the POMC gene. Patients were diagnosed based on the clinical trials of red hair, adrenal insufficiency, and early-onset severe obesity. One previously described translation initiation mutation (C3804A) as well as one new nonsense (A6851T) and two new frame-shift mutations (6996del and 7100 + 2G) were found in homozygosity or compound heterozygosity. The heterozygous parents were found to have high normal or mildly elevated body weight, suggesting a dosage effect of the POMC gene product on weight regulation. To compensate for the lack of hypothalamic melanocortin function, we initiated a trial in the two previously published patients with intranasal ACTH4-10, a melanocortin fragment for which an anorexic effect has been described recently. During 3 months with increasing doses of ACTH4-10, no change of body weight or metabolic rate was observed, suggesting that at least in these two POMC-deficient patients ACTH4-10 is without any compensatory effect. In the same two patients, further investigation revealed a mildly elevated TSH. However, a 1-yr treatment with thyroid hormone did not result in a significant reduction of body weight.
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PMID:Obesity due to proopiomelanocortin deficiency: three new cases and treatment trials with thyroid hormone and ACTH4-10. 1455 33

Dyslipidemia and obesity are common in adult patients with hypopituitarism. Possible contributions of age, sex and hormone deficiencies to hypercholesterolemia and obesity in adult hypopituitary patients were analyzed in 1, 272 Japanese cases based on a database of a national survey on adult hypopituitarism. In patients on routine hormone replacement therapy, 30.5% of male and 40.7% of female subjects were considered hypercholesterolemic. In univariate analysis, hypercholesterolemia was more prevalent in female, aged, untreated Gn-deficient and TSH-deficient groups. In multivariate analysis, sex of female, age older than 40 yr and TSH deficiency were the independent contributing factors to hypercholesterolemia. Obesity (body mass index (BMI) > or = 25 kg/m2) was more prevalent in male, TSH-deficient and ADH-deficient groups. Severe obesity (BMI > or = 30) was observed in high prevalence in the youngest group. These findings suggest that hypercholesterolemia and obesity were prevalent in different age and gender groups in Japanese adult patients with hypopituitarism. Insufficient replacement of thyroid hormone and possibly gonadotropin deficiency might contribute to hypercholesterolemia. In contrast, hypothalamic dysfunction as well as hormone deficiencies might play roles in obesity in these patients.
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PMID:Hypercholesterolemia and obesity in adult patients with hypopituitarism: a report of a nation-wide survey in Japan. 1470 49

Growth, development, and maturation of adipose tissue in the fetus can determine both survival at birth as well as having longer term consequences for adult disease. The mitochondrial proteins uncoupling protein (UCP) 1, voltage dependent anion channel (VDAC), and cytochrome c have an important role in cellular energy regulation. Activity of these proteins is particularly important during the transition from fetal to neonatal life when cellular energy requirements are at near maximal rates. The regulation of these proteins by endocrine factors is highly complex and may be dependent on both fetal number and maternal nutrition. The cytokine hormones leptin and prolactin have well established functions in energy regulation and lactation respectively. However, recent data proposes a role in regulation of mitochondrial proteins, particularly UCP1, and thermogenesis. Cortisol is an adrenal hormone with a critical role in fetal tissue maturation, especially the lung. It has now been shown to influence the abundance of UCP1 in the fetus, a role that may in part be regulated by the metabolically active thyroid hormone triiodothyronine. A greater understanding of the regulation of mitochondrial proteins within adipose tissue by endocrine and nutritional factors is likely to be important in preventing neonatal morbidity and mortality. It could also add substantially to our understanding of pathological conditions such as obesity and non-insulin dependent diabetes.
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PMID:Hormonal and nutritional regulation of adipose tissue mitochondrial development and function in the newborn. 1475 65

The orphan nuclear receptor CAR (NR1I3) has been characterized as a central component in the coordinate response to xenobiotic and endobiotic stress. In this study, we demonstrate that CAR plays a pivotal function in energy homeostasis and establish an unanticipated metabolic role for this nuclear receptor. Wild-type mice treated with the synthetic CAR agonist 1,4-bis[2-(3,5-dichloropyridyloxy)]benzene (TCPOBOP) exhibited decreased serum concentration of the thyroid hormone (TH) thyroxine (T(4)). However, treatment of Car(-/-) mice with TCPOBOP failed to elicit these changes. To examine whether CAR played a role in the regulation of TH levels under physiological conditions, wild-type and Car(-/-) mice were fasted for 24 h, a process known to alter TH metabolism in mammals. As expected, the serum triiodothyronine and T(4) concentrations decreased in wild-type mice. However, triiodothyronine and T(4) levels in fasted Car(-/-) mice remained significantly higher than those in fasted wild-type animals. Concomitant with the changes in serum TH levels, both CAR agonist treatment and fasting induced the expression of CAR target genes (notably, Cyp2b10, Ugt1a1, Sultn, Sult1a1, and Sult2a1) in a receptor-dependent manner. Importantly, the Ugt1a1, Sultn, Sult1a1, and Sult2a1 genes encode enzymes that are capable of metabolizing TH. An attenuated reduction in TH levels during fasting, as observed in Car(-/-) mice, would be predicted to increase weight loss during caloric restriction. Indeed, when Car(-/-) animals were placed on a 40% caloric restriction diet for 12 weeks, Car(-/-) animals lost over twice as much weight as their wild-type littermates. Thus, CAR participates in the molecular mechanisms contributing to homeostatic resistance to weight loss. These data imply that CAR represents a novel therapeutic target to uncouple metabolic rate from food intake and has implications in obesity and its associated disorders.
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PMID:The nuclear receptor CAR is a regulator of thyroid hormone metabolism during caloric restriction. 1500 31

In mammals, thyroid hormone responsive Spot 14 (THRSP) is a small acidic protein that is predominately expressed in lipogenic tissue (i.e., liver, abdominal fat and the mammary gland). This gene has been postulated to play a role in lipogenesis, since it responds to thyroid hormone stimulation, high glucose levels and it is localized to a chromosomal region implicated in obesity. In this paper, we report the identification and characterization of duplicated polymorphic paralogs of Spot 14 in the chicken, THRSPalpha and THRSPbeta. Despite low similarity in amino acid (aa) sequence between chickens and mammals, other properties of Spot 14 (i.e., pI, subcellular localization, transcriptional control and functional domains) appear to be highly conserved. Furthermore, a synteny group of THRSP and its flanking genes [NADH dehydrogenase (NDUFC2) and glucosyltransferase (ALG8)] appears to be conserved among chickens, humans, mice and rats. Polymorphic alleles, involving a variable number of tandem repeats (VNTR), were discovered in the putative protein coding region of the duplicated chicken THRSPalpha (9 bp) and THRSPbeta (6 or 12 bp) genes. Our study shows that the THRSPalpha locus is associated with abdominal fat traits in a broilerxLeghorn resource population.
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PMID:Duplicated Spot 14 genes in the chicken: characterization and identification of polymorphisms associated with abdominal fat traits. 1514 57

An excess of thyroid hormone (TH) leads to a mix of deleterious (increased heart rate, muscle wasting and osteoporosis) and beneficial effects (reduced serum cholesterol and lipoprotein A and weight loss). All of these actions are mediated by nuclear thyroid hormone receptors (TRs), however, genetic evidence suggests that different TR isoforms do not contribute equally to individual TH effects. Thus, TR isoform selective activators could mimic the beneficial aspects of TH excess while avoiding the harmful effects. This article reviews new selective TR activators, their mechanism of action (they work by targeting the TR-beta isoform) and their actions in animal models. It is clear that these compounds represent a promising new avenue for the treatment of lipid disorders and obesity.
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PMID:Selective activators of thyroid hormone receptors. 1515 24

It is well known that obesity is associated with increased bone mineral density. Although this phenomenon has been explained to be attributable to the mechanical burden, there have been increasing evidences indicating that some humoral factor ie. 'hormone', especially adiposity signal such as insulin or leptin, may play a role in disorders of bone metabolism associated with obesity. There have been several evidences suggesting that other hormones such as thyroid hormone, growth hormone, or glucocorticoid may also be involved.
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PMID:[Obesity and bone metabolism]. 1557 80

Skeletal muscle is a major glucose-utilizing tissue in the absorptive state and the major glucose transporter expressed in muscle in adulthood is GLUT4. GLUT4 expression is exquisitely regulated in muscle and this seems important in the regulation of insulin-stimulated glucose uptake by this tissues. Thus, muscle GLUT4 overexpression in transgenic animals ameliorates insulin resistance associated with obesity or diabetes. Recent information indicates that glut4 gene transcription is regulated by a number of factors in skeletal muscle that include MEF2, MyoD myogenic proteins, thyroid hormone receptors, Kruppel-like factor KLF15, NF1, Olf-1/Early B cell factor and GEF/HDBP1. In addition, studies in vivo indicate that under normal conditions the activity of the muscle-specific GLUT4 enhancer is low in adult skeletal muscle compared with the maximal potential activity that it can attain at high levels of the MRF transcription factors, MEF2, and TRalpha1. This finding indicates that glut4 transcription may be greatly up-regulated via activation of this enhancer through an increase in the levels of expression or activity of these transcription factors. Understanding the molecular basis of the expression of glut4 will be useful for the appropriate therapeutic design of treatments for insulin-resistant states. The nature of the intracellular signals that mediate the stimulation of glucose transport in response to insulin or exercise is also reviewed.
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PMID:Mechanisms regulating GLUT4 glucose transporter expression and glucose transport in skeletal muscle. 1565 19


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