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

Insulin and insulin-like growth factor (IGF) axes are major determinants of proliferation and apoptosis and thus may influence carcinogenesis. In various animal models, modulation of insulin and IGF-1 levels through various means, including direct infusion, energy excess or restriction, genetically induced obesity, dietary quality including fatty acid and sucrose content, inhibition of normal insulin secretion and pharmacologic inhibition of IGF-1, influences colonic carcinogenesis. Human evidence also associates high levels of insulin and IGF-1 with increased risk of colon cancer. Clinical conditions associated with high levels of insulin (noninsulin-dependent diabetes mellitus and hypertriglyceridemia) and IGF-1 (acromegaly) are related to increased risk of colon cancer, and increased circulating concentrations of insulin and IGF-1 are related to a higher risk of colonic neoplasia. Determinants and markers of hyperinsulinemia (physical inactivity, high body mass index, central adiposity) and high IGF-1 levels (tall stature) are also related to higher risk. Many studies indicate that dietary patterns that stimulate insulin resistance or secretion, including high consumption of sucrose, various sources of starch, a high glycemic index and high saturated fatty acid intake, are associated with a higher risk of colon cancer. Although additional environmental and genetic factors affect colon cancer, the incidence of this malignancy was invariably low before the technological advances that rendered sedentary lifestyles and obesity common, and increased availability of highly processed carbohydrates and saturated fatty acids. Efforts to counter these patterns are likely to have the most potential to reduce colon cancer incidence, as well as cardiovascular disease and diabetes mellitus.
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PMID:Insulin, insulin-like growth factors and colon cancer: a review of the evidence. 1216 83

Adiponectin (ApN) is thought to play a major role in the pathogenesis of the Metabolic Syndrome. Production of ApN and regulation of its related gene (apM1) have not yet been studied in human visceral adipose tissue. ApN was mainly associated with adipocyte membranes and abundantly secreted in medium from isolated adipocytes. apM1 gene expression, restricted to the adipocyte fraction of adipose tissue, decreased spontaneously when adipose explants were cultured in basal medium for 24 h while the expression of other adipose genes barely changed (PPARgamma, GAPDH) or increased (PAI-1). Unexpectedly, the fall of apM1 mRNA was prevented by the addition of actinomycin D, an inhibitor of transcription, or cycloheximide, an inhibitor of protein synthesis, and by reducing the amount of adipose tissue cultured per dish, thereby suggesting that a newly synthesized factor released by adipose tissue destabilizes apM1 mRNA. apM1 gene expression was also negatively regulated by glucocorticoids and positively by insulin and IGF-1. This regulation could contribute to the decreased apM1/ApN levels in insulin-resistant patients with obesity and the Metabolic Syndrome.
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PMID:Secretion of adiponectin and regulation of apM1 gene expression in human visceral adipose tissue. 1170 24

The metabolic syndrome is associated with a marked increase in risk of type 2 diabetes and atherosclerotic vascular disease (AVD). The mechanism responsible for the metabolic syndrome is uncertain, but recent evidence suggests that a combination of low birth weight and adult obesity is associated with a markedly increased prevalence. Insulin resistance is the cardinal feature of the metabolic syndrome. Several hormones, have modes of action that either potentiate or reduce the biological actions of insulin and, therefore, attenuate or induce insulin resistance. Since insulin action may be modified, these hormones potentially contribute to the pathogenesis of the metabolic syndrome. The purpose of this review is to discuss programming of hormones that modulate insulin action. The review focuses on two major endocrine pathways: (i) glucocorticoid hormone action; and (ii) the growth hormone (GH)-insulin-like growth factor (IGF-1) axis, and discusses mechanisms linking abnormal activity of these pathways with reduced early growth, adult obesity and the metabolic syndrome.
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PMID:Programming other hormones that affect insulin. 1180 24

Obesity and starvation have opposing affects on normal physiology and are associated with adaptive changes in hormone secretion. The effects of obesity and starvation on thyroid hormone, GH, and cortisol secretion are summarized in Table 1. Although hypothyroidism is associated with some weight gain, surveys of obese individuals show that less than 10% are hypothyroid. Discrepancies have been reported in some studies, but in untreated obesity, total and free T4, total and free T3, TSH levels, and the TSH response to TRH are normal. Some reports suggest an increase in total T3 and decrease in rT3 induced by overfeeding. Treatment of obesity with hypocaloric diets causes changes in thyroid function that resemble sick euthyroid syndrome. Changes consist of a decrease in total T4 and total and free T3 with a corresponding increase in rT3. untreated obesity is also associated with low GH levels; however, levels of IGF-1 are normal. GH-binding protein levels are increased and the GH response to GHRH is decreased. These changes are reversed by drastic weight reduction. Cortisol levels are abnormal in people with abdominal obesity who exhibit an increase in urinary free cortisol but exhibit normal or decreased serum cortisol and normal ACTH levels. These changes are explained by an increase in cortisol clearance. There is also an increased response to CRH. Treatment of obesity with very low calorie diets causes a decrease in serum cortisol explained by a decrease in cortisol-binding proteins. The increase in cortisol secretion seen in patients with abdominal obesity may contribute to the metabolic syndrome (insulin resistance, glucose intolerance, dyslipidemia, and hypertension). States of chronic starvation such as seen in anorexia nervosa are also associated with changes in thyroid hormone, GH, and cortisol secretion. There is a decrease in total and free T4 and T3, and an increase in rT3 similar to findings in sick euthyroid syndrome. The TSH response to TRH is diminished and, in severe cases, thyroid-binding protein levels are decreased. In regards to GH, there is an increase in GH secretion with a decrease in IGF-1 levels. GH responses to GHRH are increased. The [table: see text] changes in cortisol secretion in patients with anorexia nervosa resemble depression. They present with increased urinary free cortisol and serum cortisol levels but without changes in ACTH levels. In contrast to the findings observed in obesity, the ACTH response to CRH is suppressed, suggesting an increased secretion of CRH. The endocrine changes observed in obesity and starvation may complicate the diagnosis of primary endocrine diseases. The increase in cortisol secretion in obesity needs to be distinguished from Cushing's syndrome, the decrease in thyroid hormone levels in anorexia nervosa needs to be distinguished from secondary hypothyroidism, and the increase in cortisol secretion observed in anorexia nervosa requires a differential diagnosis with primary depressive disorder.
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PMID:Effect of obesity and starvation on thyroid hormone, growth hormone, and cortisol secretion. 1205 88

Obesity-linked type 2 diabetes is a disease of insulin resistance combined with pancreatic beta-cell dysfunction. Although a role for beta-cell mass in the pathogenesis of obesity-linked type 2 diabetes has recently gained prominence, the idea is still being developed. It is proposed that in early obesity an increase in beta-cell mass and function might compensate for peripheral insulin resistance. However, as time and/or the severity of the obesity continue, there is decay in such adaptation and the beta-cell mass becomes inadequate. This, together with beta-cell dysfunction, leads to the onset of type 2 diabetes. It is becoming evident that elements in insulin and insulin growth factor (IGF)-1 signal-transduction pathways are key to regulating beta-cell growth. Current evidence indicates that interference of insulin signaling in obesity contributes to peripheral insulin resistance. This article examines whether a similar interference of IGF-1 signaling in the beta-cell could hinder upregulation of beta-cell mass and/or function, resulting in a failure to compensate for insulin resistance.
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PMID:Pancreatic beta-cell growth and survival--a role in obesity-linked type 2 diabetes? 1212 23

Obesity is associated with considerably reduced plasma GH concentrations, which may contribute to anovulation in (obese) women with polycystic ovary disease (PCOS). This clinical investigation was undertaken to establish whether the GH release process is deranged in obese women with PCOS and, if so, whether the observed anomalies are features of the syndrome or a sequel of body fat accretion. To this end we sampled 24-h plasma GH concentration profiles at 10-min intervals in 15 obese PCOS patients [mean age, 29 yr (range, 20-38); percent body fat, 47 +/- 5.2%], 15 equally obese controls with regular menstrual cycles [age, 34 yr (range, 20-44); percent body fat, 48 +/- 4.9%], and 15 healthy age-matched lean controls [age, 34 yr (range, 21-45); percent body fat, 29 +/- 9.0%]. Compared with lean controls, obese PCOS patients exhibited a greater than 60% reduction in basal and a greater than 75% reduction in pulsatile and total daily GH secretion due to a 2.7-fold attenuation of burst mass and a lesser (1.4-fold) slowing of GH pulse frequency. The mean +/- SEM number of statistically significant GH peaks was 13.9 +/- 1.2/24 h, the endogenous GH half-life was 14.1 +/- 0.4 min, basal GH secretion was 5.0 +/- 0.7 mU/liter.24 h, and total secretion was 61.4 +/- 9.6 mU/liter.24 h in obese women with PCOS. None of these parameters differed from those in the body mass index-matched controls. The approximate entropy ratio was significantly increased in obese women (both PCOS and controls), indicating greater irregularity of the GH release process. Total GH secretion in patients and the two control groups correlated strongly and negatively with percent body fat (r = -0.775; P < 10(-8)). Serum concentrations of IGF-I and IGF-binding protein-3 were higher in patients with PCOS than in obese controls (P = 0.03 and P = 0.02, respectively), but the IGF-1/IGF-binding protein-3 ratio was equivalent in all three study groups. In conclusion, the profoundly reduced and irregular GH release in obese women with PCOS appears to be a corollary of body fat accretion and not of the syndrome per se.
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PMID:Low amplitude and disorderly spontaneous growth hormone release in obese women with or without polycystic ovary syndrome. 1221 75

Overweight and obesity are growing problems in the world today. A recent survey shows that about 30% of the adolescent and adult Swedish population is overweight or obese. The etiology is a combination of many factors, the most important of which are physical inactivity and high caloric diet. Obese children have a normal to accelerated growth rate despite low growth hormone (GH) levels. The aim of our study was to investigate whether craniofacial morphology differs between obese adolescents and normal weight adolescents. Lateral cephalograms from 39 adolescents with obesity, aged 14-16 years, were analysed and compared with lateral cephalograms from an equal number of sex- and aged-matched controls. Compared to the controls, the subjects in the obesity group showed increased mandibular length, prognathic jaws and a reduced upper anterior face height. Despite low GH levels, obese children have normal levels of insulin-like growth factor (IGF-1). Since we found an advanced craniofacial growth in obese adolescents with low GH and high IGF-1 serum levels, craniofacial growth may be more dependent on free circulating LGF-1 than on the locally produced portion.
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PMID:Craniofacial morphology in obese adolescents. 1222 41

Hepatocyte retinoid X receptor (RXR)alpha-deficient mice and wild-type mice were fed either a regular or a high-saturated-fat diet for 12 wk to study the functional role of hepatocyte RXRalpha in fatty acid and carbohydrate metabolism. Food intake was significantly reduced in hepatocyte RXRalpha-deficient mice when either diet was used. The amount of food intake was negatively associated with serum leptin level. Although mutant mice ate less, body weight and fat content were significantly higher in mutant than wild-type mice. Examination of the expression of peroxisome proliferator-activated receptor-alpha target genes indicated that the peroxisome proliferator-activated receptor-alpha-mediated pathway was compromised in the mutant mice, which, in turn, might affect fatty-acid metabolism and result in increased body weight and fat content. Although mutant mice were obese, they demonstrated the same degree of insulin sensitivity and the same level of serum insulin as the wild-type mice. However, these mutant mice have improved glucose tolerance. To explore a mechanism that may be responsible for the improved glucose tolerance, serum IGF-I level was examined. Serum IGF-1 level was significantly increased in mutant mice compared with wild-type mice. Taken together, hepatocyte RXRalpha deficiency increases leptin level and reduces food intake. Those mice also develop obesity, with an unexpected improvement of glucose tolerance. The result also suggests that an increase in serum IGF-I level might be one of the mechanisms leading to improved glucose tolerance in hepatocyte RXRalpha-deficient mice.
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PMID:Hepatocyte retinoid X receptor-alpha-deficient mice have reduced food intake, increased body weight, and improved glucose tolerance. 1253 23

Factors that modulate catch up growth influence the quantity and quality of the recovered tissue. Insulin and IGF-1 respond to dietary changes in carbohydrates and proteins; evidence shows that IGF-1 and leptin may be good indicators of nutritional recovery. The optimal diet to promote catch up growth is still controversial. There is consensus on the need to adjust the energy-protein intake to the growth velocity observed, without encouraging excessive eating, to avoid obesity. Zinc supplementation and physical activity appear as relevant factors to promote the synthesis of lean mass. In some models of early malnutrition, a better catch up growth during childhood, is associated with a higher frequency of chronic diseases and mortality in adulthood. In this context, we will review some factors that seem relevant to the modulation of catch up growth, which should be taken into account when reviewing the therapeutic guidelines to treat malnourished children.
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PMID:[Nutritional recovery. An unresolved challenge]. 1270 62

States of hyperinsulinemia with insulin resistance are frequently associated with proliferative tissue abnormalities, via stimulation of DNA synthesis and cell proliferation through the IGF-1 receptor. Such elements of metabolic syndrome (hyperinsulinemia/insulin-resistance, obesity, type 2 diabetes mellitus, hypertension, dyslipidemia) are explored in a population of 125 women (n. 50 with histologically confirmed diagnosis of breast cancer, Group A; n. 50 with benign breast pathology, Group B; n. 25 with no breast pathology, Group C, controls), affering to a Center for the prevention of breast cancer, in order to investigate for an eventual relationship between these pathologies. The prevalence of type 2 diabetes mellitus, hypertension, dyslipidemia, was higher in group of women affected by breast cancer vs. benign breast pathology and controls. This finding is in agreement with the hypothesis of the interrelationship of hyperinsulinism/insulin resistance with the growth-related abnormalities of breast cancer.
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PMID:Metabolic syndrome and breast cancer risk. 1270 11


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