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

Recent theories propose that a Western lifestyle may increase cancer risk through alterations in the metabolism of insulin and insulin-like growth factors (IGF: McKeown-Eyssen, 1994; Giovannucci, 1995; Kaaks, 19%; Werner & LeRoith, 1996). Insulin regulates energy metabolism, and increases the bioactivity of IGF-I, by enhancing its synthesis. and by decreasing several of its binding proteins (IGFBP; IGFBP-1 and -2). Insulin and IGF-I both stimulate anabolic processes as a function of available energy and elementary substrates (e.g. amino acids). The anabolic signals by insulin or IGF-I can promote tumour development by inhibiting apoptosis, and by stimulating cell proliferation. Furthermore, both insulin and IGF-I stimulate the synthesis of sex steroids, and inhibit the synthesis of sex hormone-binding globulin (SFIBG), a binding protein that regulates the bioavailability of circulating sex steroids to tissues. The present paper reviews epidemiological findings relating the risk of cancers of the colo-rectum, pancreas, breast, endometrium and prostate to body size (obesity, height) and physical activity, and discusses the relationships between obesity and physical activity and plasma levels of insulin, IGF-I and IGFBP. Subsequent sections review epidemiological findings relating cancer risk to indices of chronic hyperinsulinaemia, and to plasma levels of IGF-I and IGFBP. Conclusions are that chronic hyperinsulinaemia may be a cause of cancers of the colon, pancreas and endometrium, and also possibly of the breast. On the other hand, elevated plasma IGF-I, as total concentrations or relative to levels of IGFBP-3, appears to be related to an increased risk of prostate cancer, breast cancer in young women, and possibly cob-rectal cancer. For cancers of the endometrium, breast and prostate, these findings are discussed in the context of relationships between insulin and IGF-I and levels of bioavailable sex steroids.
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PMID:Energy balance and cancer: the role of insulin and insulin-like growth factor-I. 1131 Apr 28

This study sought to examine the potential influence of personality disorders (PD) on anthropometry, hormones and metabolism in women. In a population sample of women born in 1956 (no.=270), estimates of PD:s by Structured Clinical Interview for DSM-III-R, Axis II, were correlated with anthropometric, endocrine, and metabolic factors. The PD:s were grouped into three thematic clusters: cluster A (characterized by oddness or eccentricity), cluster B (characterized by self-centeredness, emotionality, and erratic behavior) and cluster C (characterized by anxiety and fear). Subjects with cluster A PD:s had significantly increased body mass index (BMI, kg/m2) and abdominal sagittal diameter (cm) as well as lower salivary cortisol after dexamethasone (DEX) compared to controls. Subjects with cluster B also had a significantly higher abdominal sagittal diameter and significantly lower salivary cortisol levels after DEX than controls. In addition, subjects with cluster B PD:s had decreased levels of ACTH, and significantly higher concentrations of lactate and triglycerides, while high-density lipoprotein (HDL) cholesterol was significantly lower compared to controls. A significantly higher waist/hip ratio was seen among subjects with cluster C PD:s. In addition, these subjects had higher levels of insulin, glucose, lactate, triglycerides, total cholesterol and low-density lipoprotein (LDL) cholesterol than controls. Moreover, IGF-I and HDL cholesterol were significantly decreased in the former group. These results suggest that PD:s are involved in the development of obesity and abdominal fat accumulation in women, with different endocrine and metabolic profiles depending on the type of PD.
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PMID:Relationships between personality disorders and anthropometry, hormones and metabolism in women. 1131 44

The aim of this study was to evaluate the GH-releasing activity of a synthetic hexapeptide, GHRP-6, in the Prader-Willi syndrome (PWS). Sixteen PWS patients (7 males and 9 females, aged 12.7-38.3 yr), 15 with essential obesity (OB) (7 males and 8 females, aged 12.9-42.9 yr), and 8 short normal children (SN; 3 males and 5 females, aged 10.2-14.3 yr) underwent 2 tests on separate occasions, being challenged with GHRP-6 (1 microg/kg, iv) or GHRH (1 microg/kg, iv)+PD (60 or 120 mg for children or adults, po). Moreover, in 11 patients with PWS and in the group of SN, the GH response to at least 2 stimulation tests had been previously determined. GH was analyzed either as mean peak values (GHp, mcg/l), or as the area under the curve (AUC, mcg/l/h) and the net incremental area under the curve (nAUC, mcg/l/h). In the group of PWS subjects, GH responses to both GHRP-6 (GHp: 11.4+/-2.0; AUC: 588+/-113; nAUC: 483+/-108) and GHRH+PD (GHp: 7.3+/-1.8; AUC: 486+/-122; nAUC: 371+/-250) were significantly lower than those observed either in OB (GHRP-6: GHp: 25.7+/-3.2, p<0.003; AUC: 1833+/-305, p<0.005; nAUC: 1640+/-263, p<0.0001. GHRH+PD: GHp: 15.1+/-2.4, p<0.009; AUC: 1249+/-248, p<0.003; nAUC: 918+/-230, p<0.006) or in SN patients (GHRP-6: GHp: 39.1+/-3.1, p<0.0001; AUC: 2792+/-158, p<0.0001; nAUC: 2705+/-165, p<0.00005. GHRH+PD: GHp: 27.5+/-3.7, p<0.0001; AUC: 1873+/-251, p<0.0001; nAUC: 1692+/-219, p<0.0005). Unlike control groups, in PWS patients GH levels after GHRP-6 did not differ from those obtained after GHRH+PD. Interestingly, low IGF-I values were present in all PWS subjects. Furthermore, no patient with PWS showed normal GH response to the previously performed GH stimulation tests. As already reported, GH release after GHRP-6 or GHRH+PD was significantly lower in OB than in SN subjects. In conclusion, our data indicate that: 1) GH response to GHRP-6 is clearly impaired in PWS; 2) the blunted GH responses to the provocative stimuli in PWS are not an artifact of obesity; 3) short stature in PWS is caused by a complex dysfunction of the hypothalamo-pituitary structures.
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PMID:Impairment of GH responsiveness to GH-releasing hexapeptide (GHRP-6) in Prader-Willi syndrome. 1140 54

Kidney dysfunction and mesangial enlargement are consequences of obesity found in Zucker rats. This study examines some of the early mechanisms by which the kidneys of Zucker rats undergo these changes. Our study shows that the glomerular planar area in the genetically obese Zucker rat undergo enlargement as early as 12 weeks of life, compared to the lean controls. This suggests mesangial proliferation is already occurring at this time, earlier than previously shown. The mRNA expression for IGF-I, and GHR in the kidney and liver of the obese Zucker rats were significantly reduced compared to the lean controls. However, the mRNA of the IGF-IR was significantly elevated in the kidney of the obese Zucker rats. The increase in kidney IGF-1R mRNA in the obese Zucker rat may suggest an increase in IGF-1 binding leading to the kidney hypertrophy observed in these rats.
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PMID:mRNA expression for insulin-like growth factor 1, receptors of growth hormone and IGF-1 and transforming growth factor-beta in the kidney and liver of Zucker rats. 1144 85

As compared to subcutaneous adipocytes, visceral adipocytes have high basal lipolysis, are highly sensitive to catecholamines, and are poorly sensitive to insulin; these traits are amplified when visceral adipocytes hypertrophy. As a result, enlarged visceral fat stores tend to flood the portal circulation with free fatty acids at metabolically inappropriate times when fatty acids are unlikely to be oxidized, thus exposing tissues to excessive free fatty acid levels and giving rise to the insulin resistance syndrome. A logical approach to preventing or correcting visceral obesity is to down-regulate the lipoprotein lipase (LPL) activity of visceral adipocytes relative to that expressed in subcutaneous adipocytes and skeletal muscle. IGF-I activity appears to be a primary determinant of visceral LPL activity in humans; systemic IGF-I activity is decreased when diurnal insulin secretion is low, when hepatocytes detect a relative paucity of certain essential amino acids, and when estrogens are administered orally. The ability of alpha-glucosidase inhibitor therapy to selectively reduce visceral adiposity suggests that down-regulation of diurnal insulin secretion and/or IGF-I activity may indeed have a greater impact on LPL activity in visceral fat than in subcutaneous fat. Thus, low-glycemic-index, vegan, high-protein, or hypocaloric diets can be expected to decrease visceral LPL activity, as can postmenopausal estrogen therapy. Furthermore, estrogen enhances the LPL activity of non-pathogenic gluteofemoral fat cells, whereas testosterone decreases visceral LPL activity in men; this may explain why sex hormone replacement in middle-aged people of both sexes has a favorable impact on visceral fat and insulin sensitivity. Beta-adrenergic activity suppresses transcription of LPL in adipocytes; this phenomenon may contribute to the favorable impact of exercise training on visceral obesity; conceivably, preadministration of safe drugs that boost catecholamine activity (caffeine, yohimbine) could potentiate this beneficial effect of exercise. Glucocorticoids selectively increase the LPL activity of visceral adipocytes; while there is currently no convincing evidence that psychological stress is a major determinant of visceral adiposity, or that stress management techniques can help to correct visceral obesity, reports that anxiolytic therapy can improve glycemic control in type 2 diabetes should encourage further research along these lines.
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PMID:Modulation of adipocyte lipoprotein lipase expression as a strategy for preventing or treating visceral obesity. 1146 Nov 72

Autosomal dominantly inherited isolated GH deficiency is caused by mutations of GH-1 that alter the normal structure of GH. We studied 16 familial cases and 1 sporadic case with isolated GH deficiency type II from 1 Dutch and 4 German families by direct sequencing of PCR-amplified genomic DNA and ectopic transcript analysis of lymphocyte mRNA. In addition, the clinical data of the affected individuals were analyzed. Two previously reported mutations and 1 novel splice site mutation in intron III of GH-1 (+1G to C and +1G to A; new, +2T to C) were detected that cause exon 3 skipping. We also discovered a novel G6191 to T missense mutation in exon 4 of GH-1 that changes valine 110, which is highly conserved in mammalian and several nonmammalian GH, to phenylalanine. Splicing of the primary RNA transcript was not affected by this mutation, which is very likely to alter the normal GH structure at the protein level. The onset of growth failure was earlier, and the degree was more severe in affected children with GH-1 splice site mutations compared with those in children with the GH-1 missense mutation. In addition, the severity of the phenotype was variable, even within the same family. The age at diagnosis was between 0.8-9.6 yr (median, 5.1 yr); height at diagnosis was between -2.5 and -8.1 SD score (median, -4.0). Most of the children were lean at diagnosis, with a body mass index ranging from -1.7 to +3.3 SD score (median, -0.5). The 5 affected adults had final heights between -1.8 and -4.5 SD score (median, -3.6), centripetal obesity, and muscular hypotrophy. Before therapy, IGF-I and IGF-binding protein-3 serum levels of all affected children were severely diminished (<<5th percentiles for age). The maximum GH peak in a total of 25 stimulation tests was between 0.1-5.0 microg/liter (median, 0.9), indicating severe GH deficiency. The height of the adenohypophysis studied by magnetic resonance imaging was normal in 2 affected children and mildly decreased in 2 others. Substitution with GH resulted in good catch-up growth in all treated children. Children with severe GH and IGF-I deficiencies, but normal size of the adenohypophysis should be examined for GH-1 splice site and missense mutations. The observed discrepancy between the very homogeneous hormone data proving severe GH and IGF-I deficiencies and the high variability of growth failure even within the same family suggests that the onset and predominance of GH-dependent growth during infancy are individually different and modified by as yet unknown factors.
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PMID:Isolated GH deficiency with dominant inheritance: new mutations, new insights. 1150 27

The discovery of a link between in utero experience and later metabolic and cardiovascular disease is one of the most important advances in epidemiology research of recent years. There is increasing evidence that alterations in the fetal environment may have long-term consequences on cardiovascular, metabolic, and endocrine pathophysiology in adult life. This process has been termed programming, and we have shown that undernutrition of the mother during gestation leads to programming of hyperphagia, obesity, hypertension, hyperinsulinemia, and hyperleptinemia in the offspring. Using this model of maternal undernutrition throughout pregnancy combined with postnatal hypercaloric nutrition of the offspring, we examined the effects of IGF-I therapy. Virgin Wistar rats (age 75 +/- 5 d, n = 20 per group) were time mated and randomly assigned to receive food either ad libitum or 30% of ad libitum intake (UN) throughout pregnancy. At weaning, female offspring were assigned to one of two diets (control or hypercaloric [30% fat]). Systolic blood pressure was measured at day 175 and following infusion with 3 microg/g per day recombinant human IGF-1 (rh-IGF-I) by minipump for 14 d. Before treatment, UN offspring were hyperinsulinemic, hyperleptinemic, hyperphagic, obese, and hypertensive on both diets, compared with ad libitum offspring and this was exacerbated by hypercaloric nutrition. IGF-I treatment increased body weight in all treated animals. However, systolic blood pressure, food intake, retroperitoneal and gonadal fat pad weights, and plasma leptin and insulin concentrations were markedly reduced with IGF-I treatment. IGF-I treatment resulted in a 3- to 5-fold increase in 38--44 kDa and 28--30 kDa IGF binding proteins, although in UN animals, there was an impaired and differential up-regulation of these insulin-like growth factor binding proteins following IGF-I treatment. The 24-kDa IGF binding protein representing IGF binding protein-4 was down-regulated in all IGF-I-treated animals, but the decrease was more marked in UN animals. Our data suggest that IGF-I treatment alleviates hyperphagia, obesity, hyperinsulinemia, hyperleptinemia, and hypertension in rats programmed to develop the metabolic syndrome X.
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PMID:IGF-I treatment reduces hyperphagia, obesity, and hypertension in metabolic disorders induced by fetal programming. 1151 75

Previous cross-sectional studies show that puberty is associated with a reduction in insulin sensitivity (S(I)), but no longitudinal studies have examined this change in detail. This study is a longitudinal study in 60 children (33 male and 27 female subjects; 32 Caucasian and 28 African-American) examined at Tanner stage I (age 9.2 +/- 1.4 years) and after 2.0 +/- 0.6 years of follow-up, by which time 29 children remained at Tanner stage I and 31 had progressed to Tanner stage III or IV. Tanner stage was assessed by physical examination. S(I), the acute insulin response (AIR), and the disposition index (DI) were determined by the tolbutamide-modified intravenous glucose tolerance test and minimal modeling, body fat mass was assessed by dual-energy X-ray absorptiometry, visceral fat was determined by computed tomography, and fasting blood was analyzed for hormone levels. In children progressing to Tanner stage III, S(I) fell significantly by 32% (4.4 +/- 3.0 to 3.0 +/- 1.7 x 10(-4)min(-1)/[microIU/ml]), AIR increased by 30%, DI fell by 27%, and there was a significant increase in fasting glucose (93.5 +/- 5.0 to 97.0 +/- 4.1 mg/dl) and insulin (14.3 +/- 8.1 to 18.6 +/- 11.0 microIU/ml). In children remaining at Tanner stage I, there was a slight increase in S(I) (6.4 +/- 3.1 to 7.4 +/- 3.5 x 10(-4)min(-1)/[microIU/ml]) with no significant change in AIR or fasting glucose and insulin. The pubertal fall in S(I) was more consistent in African-Americans; remained significant after controlling for age, sex, and change in fat mass, visceral fat, and fat-free mass; and was similar in children at low, medium, and high body fat. Change in S(I) was not significantly related to change in fasting hormone levels, but change in AIR was significantly related to change in androstendione (r = 0.39; P = 0.04). Pubertal transition from Tanner stage I to Tanner stage III was associated with a 32% reduction in S(I,) and increases in fasting glucose, insulin, and AIR. These changes were similar across sex, ethnicity, and obesity. The significant fall in DI suggests conservation in beta-cell function or an inadequate beta-cell response to the fall in S(I). The fall in S(I) was not associated with changes in body fat, visceral fat, IGF-I, androgens, or estradiol.
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PMID:Longitudinal study on pubertal insulin resistance. 1167 20

Our aim was to investigate the effects of one year recombinant human growth hormone (rhGH) therapy on the regulation by insulin of gene expression in muscle and adipose tissue in adults with secondary GH deficiency (GHD). Six GHD subjects without upper-body obesity were submitted to a 3-h euglycemic hyperinsulinemic clamp before and after one year of rhGH therapy. Muscle and abdominal subcutaneous adipose tissue biopsies were taken before and at the end of each clamp. The mRNA levels of insulin receptor, p85 alpha-phosphatidylinositol-3 kinase (p85 alpha PI-3K), insulin dependent glucose transporter (Glut4), hexokinase II, glycogen synthase, lipoprotein lipase (LPL) in muscle and in adipose tissue, hormone sensitive lipase and peroxisome proliferator-activated receptor gamma (PPAR gamma) in adipose tissue were quantified by RT-competitive PCR. One year treatment with rhGH (1.25 IU/day) increased plasma IGF-I concentrations (54+/-7 vs 154+/-11 ng/ml, P<0.01) but did not affect insulin-stimulated glucose disposal rate measured during the hyperinsulinemic clamp (74+/-9 vs 85+/-5 micromol/kg free fat mass/min). Insulin significantly increased p85 alpha PI-3K, hexokinase II and Glut4 mRNA levels in muscle both before and after rhGH treatment. One year of GH therapy increased LPL mRNA levels in muscle (38+/-2 vs 70+/-7 amol/microg total RNA, P<0.05) and in adipose tissue (2490+/-260 vs 4860+/-880 amol/microg total RNA, P<0.05), but did not change the expression of the other mRNAs. We conclude from this study that GH therapy did not alter whole body insulin sensitivity and the response of gene expression to insulin in skeletal muscle of adult GHD patients, but it did increase LPL expression in muscle and adipose tissue. This result could be related to the documented beneficial effect of GH therapy on lipid metabolism.
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PMID:Expression of insulin target genes in skeletal muscle and adipose tissue in adult patients with growth hormone deficiency: effect of one year recombinant human growth hormone therapy. 1169 48

Growth hormone (GH) and insulin-like growth factors (IGFs) play a major role in fish development and metabolism, and several studies have allowed discernment of a complex and tissue-specific collection of salmonid IGF-I transcripts (Ea-4, Ea-3, Ea-2, Ea-1), which are the result of the alternative splicing of the E-domain region. However, the pattern of IGF-I expression is different in non-salmonid fish, and only one or two transcripts (Ea-4, Ea-2) have been detected in hepatic and extrahepatic tissues of common carp, barramundi, black sea bream and gilthead sea bream. Despite this, when comparisons are made within Mediterranean fish species (European sea bass, common dentex and gilthead sea bream), plasma IGF-I levels are consistent with fish species differences in growth rates. Changes of growth rates, and plasma IGF-I and GH levels are also found in response to changes in diet composition and ration size, which may serve to assess the suitability of feeding regimes in aquaculture practice. Regulation of plasma somatolactin (SL) levels is also examined in gilthead sea bream, and the resulting plasma SL profile differs from that of GH. Thus, in contrast to GH, plasma SL levels augment with the increase of ration size and fish size (advancement of age). A transient increase in plasma SL levels is also found in short-term fasted fish, and this fish peptide may act as an anti-obesity hormone helping to expedite growth-reproductive processes following replenishment of fat stores, and/or mediate the adaptation to fasting until the lipolytic action of GH and/or other endocrine factors is fully accomplished. This agrees with the known increase of plasma SL levels during acute stress and exhaustive exercise. However, a causal link between SL and energy mobilisation (lipid metabolism) remains to be established, and further research is needed to determine the extent to which SL and GH act in a complementary manner to make available metabolic fuels and to regulate body fat mass and feeding behaviour.
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PMID:Somatotropic regulation of fish growth and adiposity: growth hormone (GH) and somatolactin (SL) relationship. 1173 31


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