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

Obesity is coupled to several disturbances of the endocrine axes. It has previously been shown that genetically obese Zucker male rats have an impaired secretion of growth hormone (GH), probably originating from a primary reduction of hypothalamic GH-releasing hormone (GHRH) function and resulting in a decrease of GH gene expression and release. We sought to evaluate the somatotropic function in another model of experimental obesity. Normal male Sprague-Dawley rats were fed an energy-rich highly palatable diet for 7 months until they reached body weights overlapping those reported for obese Zucker rats. They were then evaluated for different indices of the hypothalamo-pituitary-somatomedin-C (IGF-I) axis. At the end of the overfeeding period, rats were divided into overtly obese (obese group) and overweight (overweight group) rats according to the degree of overweight and the Obesity Lee Index, while rats fed ad libitum with the standard pellet chow served as controls. Acute administration of a supramaximal dose of GHRH (2 micrograms/rat i.v.) elicited a significantly (at least P < 0.05) lower plasma GH rise in the overweight and obese groups compared with the controls although no difference was seen in the pituitary GH content and gene expression and plasma concentrations of free IGF-I in the two experimental groups vs the controls. In addition, evaluation of hypothalamic GHRH and somatostatin mRNAs (slot-blot hybridization) did not show any significant differences between the three groups. Of the different metabolic indices investigated, plasma glucose and insulin concentrations were significantly (P < 0.01) higher in the obese than in the overweight and control groups. A sharp decrease in plasma testosterone levels, together with a reduction in testis weight, was seen in both groups of rats fed the palatable diet compared with the controls. These findings underline the 'peripheral' feature of the hyposomatotropinism of rats chronically fed an energy-rich diet, and may account for the reversibility of the GH impairment in many obese subjects once a normal body weight has been restored. Moreover, the peripherally-driven hyposomatotropinism of these rats is in sharp contrast with the hypothalamic-driven GH secretory impairment of the obese Zucker rats.
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PMID:Characterization of the hypothalamo-pituitary-IGF-I axis in rats made obese by overfeeding. 869 49

Obesity, short stature, decreased growth rate and delayed skeletal maturation are common features of children with Prader-Willi syndrome (PWS). In contrast to PWS, children with simple exogenous obesity have normal or increased growth rate and normal or advanced skeletal maturation. Decreased growth hormone (GH) secretion evaluated by pharmacological or physiological testing associated with increased plasma insulin-like growth factor (IGF-I) and GH-binding protein (GH-BP) levels are also characteristic of simple obesity. In order to understand whether the suboptimal GH secretion in PWS is an artifact of the obesity, we studied 33 obese and 11 non-obese PWS children, aged 2-16 years.GH secretion was evaluated with three pharmacological stimuli (insulin, clonidine and L-dopa) and by spontaneous 24-hour GH secretion. Skeletal maturation was delayed in 70% whereas plasma IGF-I and GH-BP were either low or normal. Forty subjects, including ten non-obese children, had GH deficiency by standard testing (failure to respond to two pharmacological stimuli), and all but one had blunted spontaneous 24-h GH secretion. No significant correlation between body mass index (wt/ht2) and spontaneous 24-h GH secretion (r = 0.145), p > 0.06) or GH-BP levels (r = 0.19, p > 0.07) was found. Thirty documented GH deficient children have completed at least two years of GH therapy. With treatment the overall mean height SD and weight SD changed from -2.2 to -0.8 and from 3.5 to 2.4 respectively (p < 0.0001). No patient has developed diabetes mellitus. In conclusion, growth velocity, skeletal maturation, GH secretion and GH dependent proteins in PWS resemble GH deficiency more than simple obesity. Our ongoing study suggests that GH deficiency in PWS is not an artifact of obesity. Although it is unlikely that GH deficiency is the only cause of decreased growth velocity and increased adiposity in PWS, it is a common feature and significant contributory factor. Long term observation will be required until achievement of adult height to determine whether GH therapy actually improves final height.
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PMID:Growth hormone secretion and effects of growth hormone therapy on growth velocity and weight gain in children with Prader-Willi syndrome. 888 49

The normal profile for overnight GH secretion in achondroplasia has not been previously studied. Factors that have been shown to influence GH secretion include age, obesity, sleep state, and the presence of obstructive sleep apnea (OSA). We assessed GH levels in a group of subjects with achondroplasia, during overnight polysomnography. Nineteen subjects with achondroplasia were studied at 11.3 y of age (median 6.7, range 1.8-30.9). Levels of GH were measured using time-resolved immunofluorometric assay (DELFIA, Pharmacia Biotech Inc.) and analyzed by a deconvolution method. Five subjects were restudied after treatment for OSA. Secretion rates of GH were greater in slow wave (SWS) and rapid eye movement (REM) sleep than in stage one and two (SI-II = light non-REM) sleep (p < 0.01). Total overnight GH secretion decreased with increasing age (r2 = 0.22 p < 0.04). Neither the frequency of arousals, frequency of sleep state transitions nor the severity of OSA correlated with measures of GH secretion. Levels of IGF-I correlated independently with age, body weight (percent ideal), and GH secretion rate (r2 = 0.76, p < 0.001). In a group of five subjects treated for OSA, improved respiratory distress index and reduced sleep state transitions were not associated with significant changes in GH secretion rate by sleep stage; SWS [from 0.62 +/- 0.28 mIU/L/min to 1.02 +/- 0.25 mIU/L/min (NS)] and SI-II sleep [from 0.26 +/- 0.07 mIU/L/min to 0.60 +/- 0.16 mIU/L/min (NS)]. However, in those five subjects, a GH secretion peak during the first 2 h of SWS was initially absent, appearing only after treatment of OSA (1.09 +/- 0.38 mIU/L/min) compared with (2.40 +/- 0.59 mIU/L/min (p = 0.01). A profile of overnight GH secretion is presented for subjects with achondroplasia.
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PMID:Overnight growth hormone secretion in achondroplasia: deconvolution analysis, correlation with sleep state, and changes after treatment of obstructive sleep apnea. 892 79

Uncoupling protein (UCP) is essential to the thermogenic function of brown adipose tissue (BAT). The thermogenic role of this protein is due to its capacity to uncouple oxidative phosphorylation in a regulated manner. The thermogenic potential of BAT is determined by its content of UCP. The gene encoding this protein is under complex regulation. Catecholamines, via cAMP, thyroid hormone and retinoic acid, directly stimulate the gene acting upon an upstream (-2.28/-2.49 kb) enhancer sequence, but cAMP may act upon other sequences of the gene as well. CCAAT enhancer binding proteins and peroxisome proliferation activator receptor (PPAR) gamma 2 have also been implicated in the regulation of the gene acting on discrete sequences. While the thyroid hormone response and retinoic acid response elements (TRE and RARE) have been well defined, the cAMP response elements (CRE) remain elusive. The two TREs are 27 bp apart between -2.33 kb and -2.39 kb. The synergism between cAMP and thyroid hormone seems to reside in a 39 bp sequence downstream (-2.28/-2.32 kb). The most important CRE, the RARE, a cell-specific enhancer and a putative PPAR element are all concentrated in a 90 bp regulatory element of great complexity (-2.40/-2.49 kb). Other hormones, such as insulin and glucocorticoids, and IGF-I also modulate the expression of the gene but their effects seem to be largely indirect. Understanding the regulation of the UCP gene expression may facilitate the development of interventions in obesity and related disorders.
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PMID:Regulation of the uncoupling protein gene expression. 910 May 46

We have studied the GH-insulin-like growth factor (IGF) axis in prepubertal children with exogenous obesity at the time of clinical diagnosis and at two time points during weight reduction on a calorie-restricted diet. Spontaneous GH secretion, IGF-I, free IGF-I (fIGF-I), IGF-II, their binding proteins (IGFBP-1, IGFBP-2, and IGFBP-3), and GH-binding protein (GHBP) values at the time of clinical diagnosis (n = 65), after a 25% decrease in the body mass index (BMI) expressed as the SD score (BMI SD score; n = 29), and after a diminution of at least 50% of the initial BMI SD score (n = 9) are reported. GH secretion was significantly reduced at diagnosis, and after a decrease of at least 25% in the initial BMI SD score, it returned to normal in all patients. Total IGF-I levels were not significantly different from those in controls at any point. In contrast, fIGF-1 and IGF-II levels were significantly increased, both at diagnosis and after BMI SD score reduction. Obese patients were hyperinsulinemic at diagnosis and remained so even after a 50% reduction of their BMI SD score. Serum IGFBP-1 and IGFBP-2 levels were significantly decreased at diagnosis and at the two points studied during weight reduction. Serum IGFBP-3 and GHBP levels were increased significantly at diagnosis and returned to normal levels after a reduction in the BMI SD score. A positive correlation between serum GHBP levels and BMI was found in both controls and obese patients. Serum IGFBP-3 levels correlated positively with IGF-I, fIGF-I, and IGF-II in all groups, but these correlations were weaker in the obese patients at diagnosis. IGFBP-2 correlated significantly with IGF-II only in the obese group at diagnosis (r = -0.760; P < 0.0001), but with fIGF-I in all groups. IGFBP-1 was negatively correlated with IGF-I and fIGF-I in all groups. In conclusion, the GH-IGF axis is dramatically altered in patients with exogenous obesity. However, most changes in the peripheral IGF system appear to be independent of the modifications in GH secretion. In addition, in contrast to current thought, not all of the observed abnormalities are reversed with a significant reduction in the BMI SD score.
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PMID:Multiple endocrine abnormalities of the growth hormone and insulin-like growth factor axis in prepubertal children with exogenous obesity: effect of short- and long-term weight reduction. 921 75

A large amount of research, primarily in mammals, has defined to a great extent the pleiotropic effects of the IGF system on growth, development, and intermediary metabolism. Similar elucidations in poultry were hindered to some extent by the absence of native peptides (IGF-I and IGF-II) until their purification, followed by the production of recombinant chicken IGFs. In many ways IGF physiology in birds is similar to that in other species, including but not limited to the fact that IGF-I synthesis is both GH- and GH-independent, and that autocrine-paracrine IGF action is evident. However, it is clear that several unique differences in IGF physiology exist between birds and mammals. For example, more IGF is present in the free form in chickens, and the biological responses to the IGFs is different in several metabolic pathways in birds compared to mammals. To date, no unique IGF-II receptor has been identified in birds. Despite an increasing understanding of the IGFs in aves, several important questions remain to be answered. What is the role of IGF-II in embryo development and posthatch growth? Does an IGF-II receptor entity exist in nonmammalian species? How does nutrition affect IGF-I and IGF-II gene expression, and can this information be used to enhance poultry production? What is the biochemical composition of the IGFBPs, and what are their roles in birds? Can the genetic variation present in poultry be used to positively modify IGF gene expression and physiology? How do the IGFs regulate intermediary metabolism? What is the role of the IGFs in the etiology of several disease states associated with rapid growth in poultry, including tibial dyschondroplasia, obesity, ascites, and spiking mortality syndrome? Answers to these questions are relevant to our understanding of the basic mechanisms of IGF physiology as well as possibly assisting in the amelioration of problems found in modern poultry production.
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PMID:Insulin-like growth factors in poultry. 926 60

A gender-related impairment of the somatotrophic axis is present in obese Zucker rats, female rats being better preserved than males. We showed that another animal model of obesity, i.e., male rats made obese by feeding a hypercaloric diet had a reduced function of somatotrophic axis which was likely related to impairment of gonadal function. Aim of this work was that of studying the function of somatotrophic axis in female overfed rats and comparing it to that of male rats of the previous study. Sprague-Dawley female rats were fed an energy-rich palatable diet for seven months. At the end of overfeeding, according to the degree of overweight, rats were divided into overtly obese (Obese), overweight (Overweight) and Non-Obese, i.e. rats whose weights were similar to those of controls. Rats fed ad libitum with the standard pellet chow served as controls (Controls). Acute administration of a supramaximal dose of GHRH (2 microg/rat, iv) elicited a plasma GH rise similar to that of Controls in all the groups, except in Obese which had a lower GH response. Growth hormone responses after GHRH administration were inversely related to plasma levels of free fatty acids (FFA). Pituitary GH content and gene expression as well as hypothalamic GHRH and SS mRNA content, were similar in all experimental groups and in Controls and the same was true for plasma concentrations of free IGF-I. These results indicate that, similarly to obese female Zucker rats, also overfed female rats had a better preservation of the somatotrophic axis than their male counterparts. In diet-induced obese rats, also the etiology of the impairment of somatotrophic axis seems to be gender-related i.e. due to a reduction of gonadal function in males and to an elevation of FFA in females.
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PMID:Hypothalamo-pituitary-IGF-1 axis in female rats made obese by overfeeding. 928 81

The effect of body condition per se on plasma IGFs and IGF-binding proteins (IGFBPs) and the whole-body metabolic responses to recombinant DNA-derived bovine GH (rbGH) in both the fed and the fasted state were determined in lean and dietary obese sheep (n = 6/group). Sheep at zero-energy balance and equilibrium body weight were injected s.c. for 12 days with 100 micrograms/kg rbGH immediately before their morning feeding. Before GH treatment, fasting plasma concentrations of insulin (17.0 +/- 1.9 vs 7.5 +/- 0.7 microU/ml), IGF-I (345 +/- 25 vs 248 +/- 10 ng/ml), glucose (52.6 +/- 1.1 vs 48.3 +/- 0.7 mg/dl), and free fatty acid (FFA) (355 +/- 45 vs 229 +/- 24 nmol/ml) were greater (P < 0.05) and those of GH (1.1 +/- 0.2 vs 2.6 +/- 0.3 ng/ml) were lower (P < 0.05) in obese than in lean sheep. Fasting concentrations of IGF-II and glucagon were not affected (P > 0.05) by obesity. GH concentrations were increased equivalently by 6-9 ng/ml in lean and obese sheep during GH treatment. GH caused an immediate and a marked fivefold increase in the fasting insulin level in obese sheep but only minimally affected insulin concentration in lean sheep. The increment in fasting glucose during GH treatment was greater (P < 0.05) in obese (8-12 mg/dl) than in lean (2-5 mg/dl) sheep. Frequent measurements in the first 8 h after feeding and injection of excipient (day 0) or the first (day 1) sixth (day 6) and twelfth (day 12) daily injection of GH showed that prandial metabolism in both groups of sheep was affected minimally by GH. However, GH treatment on day 1 (not days 6 or 12) acutely attenuated the feeding-induced suppression of plasma FFA in both groups of sheep and this effect was significantly greater in obese than in lean sheep. Although obese sheep were hyposomatotropic, the basal and GH-induced increases in plasma IGF-I concentrations were greater (P < 0.05) in obese than in lean sheep. Plasma IGF-II was unaffected by obesity and was not increased by GH stimulation. Western ligand blotting showed that IGFBP-3 accounted for approximately 50-60% of the plasma IGF-I binding capacity in sheep respectively both before and during GH treatment. Basal plasma levels of IGFBP-2 were lower (P < 0.05) and those of IGFBP-3 greater (P < 0.05) in obese compared with lean sheep. GH increased the level of IGFBP-3 equally in lean and obese sheep, but suppressed the expression of IGFBP-2 more (P < 0.05) in lean than in obese sheep. We concluded that the diabetogenic-like actions of GH in sheep were exaggerated markedly by obesity, and were expressed more during the fasted than the fed states. The effects of GH stimulation on the endocrine pancreas may be selective for beta-cells and preferentially enhanced by obesity. GH regulation of IGF-I and the IGFBPs differs in lean and obese sheep.
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PMID:Differential effects of GH stimulation on fasting and prandial metabolism and plasma IGFs and IGF-binding proteins in lean and obese sheep. 929 44

Neural disturbances are observed in the peripheral and central nervous systems of patients with insulin-dependent diabetes mellitus (IDDM) and non-IDDM (NIDDM). Insulin-like growth factors (IGFs) are neurotrophic growth factors that can support nerve regeneration and neuronal survival in the types of neurons known to be afflicted in diabetes. We tested the hypotheses that IGF gene expression is reduced in neural tissues and liver of spontaneously diabetic obese Zucker (fa/fa) rats and that IGF treatment can prevent neuropathy. There was a significant early reduction in IGF-II mRNA content as measured per mg of wet tissue or per poly(A)+ RNA in sciatic nerves, spinal cord and brain from spontaneously diabetic obese (fa/fa) vs. nondiabetic lean (+/+) adult rats. In addition, IGF-I mRNA content was reduced in liver but not nerve or spinal cord of NIDDM rats. Pain/pressure thresholds were abnormal (hyperalgesia) in diabetic (fa/fa) vs. nondiabetic (+/+) rats, and subcutaneous infusion of IGF-II restored thresholds toward normal. The low dose of IGF-II that prevented hyperalgesia in contrast had no effect on hyperglycemia or obesity. These data suggest that IGF treatment may provide rational therapy for diabetic neuropathy and that therapy may be effective even in patients unable to adequately control their hyperglycemia.
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PMID:Insulin-like growth factor (IGF) gene expression is reduced in neural tissues and liver from rats with non-insulin-dependent diabetes mellitus, and IGF treatment ameliorates diabetic neuropathy. 933 45

Numerous endocrine abnormalities of the growth hormone (GH)-insulin-like growth factor axis have been described in patients with both anorexia nervosa and obesity during childhood and adolescence. These alterations include changes in the levels of 24-hour spontaneous GH secretion, high-affinity, low-capacity GH binding protein (GHBP), IGF-I, IGF-II and the IGF binding proteins (IGFBPs). However, the existing information is sometimes confusing and contradictory. Furthermore, little or no data in these pathologies are available concerning IGFBP-2 or free IGF-I. We have analysed the GH-IGF axis in large populations of adolescents with anorexia nervosa and prepubertal children with exogenous obesity. These patients were studied at the time of diagnosis and at two timepoints during nutritional therapy and normal weight recovery. The results of these studies using age- and sex-matched controls are described here.
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PMID:Disturbances in the growth hormone-insulin-like growth factor axis in children and adolescents with different eating disorders. 935 Apr 40


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