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

The cytokine receptors for growth hormone (GH), prolactin and leptin have a critical role in regulating embryo, placental and/or fetal development, which is dependent on stage of gestation and species. GH and prolactin receptors are detectable from conception, and alterations in the maternal hormonal environment may impact on placental growth from this early stage of gestation. Leptin is critical for conception, but its role in fetal growth remains elusive. During late gestation, when fetal growth accelerates and organ maturation occurs, prolactin and insulin-like growth factor-I may have interactive roles in regulating the growth of specific tissues, including adipose tissue. Prolactin, leptin and GH all have specific effects on fetal and neonatal energy balance, which are mediated in part through promoting lipolysis and/or enhancing the expression of uncoupling proteins. An increased understanding of these interactions is likely to have important implications for a number of potentially pathological conditions, including infection, obesity and hypertension.
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PMID:Cytokines and cytokine receptors in fetal growth and development. 1135 22

In rodents leptin inhibits food intake, stimulates energy expenditure, reverses obesity, ameliorates insulin resistance, and accelerates sexual maturation. These potent and diverse effects have stimulated interest in exploring a role for leptin in the treatment of human metabolic disorders. However, the significance of leptin in human (patho)physiology is still being investigated. The present review summarizes current knowledge of leptin regulation, provides a critical assessment of initial experience with leptin therapy, and discusses potential targets for recombinant leptin therapy in humans. The results of numerous studies indicate that leptin is indeed a regulated human hormone: The physiological factors that influence leptin secretion include gender, adiposity, physical exercise, feeding, and caloric restriction. Several hormones, including insulin, glucocorticoids, estradiol, growth hormone, testosterone, somatostatin, and insulin-like growth factor-I also modulate leptin secretion. The results of initial trials of leptin therapy in humans have become available. Treatment with recombinant human leptin (0.028 mg/kg) induced a progressive weight loss (without evidence of tachyphylaxis) in a morbidly obese patient with congenital leptin deficiency. The weight loss averaged 1-2 kg/month, was associated with preservation of lean muscle mass, and was almost exclusively accounted for by depletion of body fat. Administration ofrecombinant leptin (0.01-0.3 mg/kg) also resultedin a dose-dependentweight loss among lean and obese humans with presumably normal leptin genotype. Thus leptin may have a therapeutic role in humans, but its physiological functions and regulation first need to be fully unravelled.
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PMID:Human leptin regulation and promise in pharmacotherapy. 1146 18

We have previously described that serum corticosteroid binding globulin (CBG) concentrations are associated with insulin secretion. The present study was designed to evaluate the effects of changing insulin concentrations, both endogenous and after exogenous insulin administration, on circulating CBG levels in vivo. Serum CBG concentrations were measured during an insulin-modified frequently sampled intravenous (IV) glucose tolerance test (FSIVGT) in 14 lean and 19 obese otherwise healthy subjects with varying degrees of glucose tolerance. Acute insulin response to glucose (AIRg) correlated significantly with serum CBG concentrations at time 0 (r = -.38, P =.029), 22 minutes (r = -.41, P =.01), 50 minutes (r = -.41, P =.01), and 180 minutes (r = -.39, P =.02). Insulin sensitivity (S(I)) was not associated with serum CBG concentration at time 0 (r = -.16, P = not significant [NS]), but correlated significantly with CBG concentration at 22 minutes (r = -.41, P =.02) and 50 minutes (r = -.35, P =.048) of the FSIVGT. In lean subjects, serum CBG concentration decreased significantly after IV insulin from 37.9 +/- 5.4 to 35.4 +/- 3 mg/L (P =.02) and returned to basal levels thereafter. In contrast, obese, glucose-tolerant subjects had lower CBG levels than lean and obese glucose intolerant subjects (33.8 +/- 3.0 v 37.9 +/- 5.4 and 39.8 +/- 4.4 mg/L, respectively), and their serum CBG concentrations remained unchanged during FSIVGT. Mean serum-free insulin-like growth factor-I (IGF-I) concentrations steadily declined from 1.21 +/- 0.81 to 0.8 +/- 0.36 microg/L during the FSIVGT, and this effect was restricted to lean subjects. Basal serum-free IGF-I did not correlate with CBG levels at time 0, but correlated inversely with the serum CBG concentrations at 22 minutes (r = -.36, P =.04). Stepwise multivariant analysis showed that AIRg (P =.035) and S(I) (P =.046), but not free IGF-I levels, independently contributed to 28% of CBG variance at 22 minutes. These results suggest that insulin, but not IGF-I, constitutes an important negative regulator of CBG liver synthesis. Endogenous and exogenous insulin do not affect serum CBG concentrations in insulin-resistant obese subjects with preserved or decreased insulin secretion. Obese glucose-tolerant subjects are hypothesized to exhibit tonically inhibited serum CBG levels. In contrast, in lean subjects, the higher the insulin secretion the lower the serum CBG concentration. The mechanisms of this CBG inhibitory effect exerted by insulin and its implication on cortisol homeostasis and fat distribution in humans await further investigations.
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PMID:Study of the effect of changing glucose, insulin, and insulin-like growth factor-I levels on serum corticosteroid binding globulin in lean, obese, and obese subjects with glucose intolerance. 1158 2

The follow-up of a large cohort of patients with Laron syndrome (LS) from infancy to adult age has enabled us to determine the effects of long-term insulin-like growth factor-I (IGF-I) deficiency on auxological, biochemical, physiological and psychological parameters. We found that early and continuous IGF-I deficiency (the anabolic effector of growth hormone) causes dwarfism, acromicria, organomicria, marked obesity, insulin resistance, retardation of skeletal maturation and osteoporosis, as well as muscular and central nervous tissue underdevelopment, and a series of biochemical changes including hypercholesterolemia. These multiple pathologies impair the quality of life of these patients. It is concluded that patients with LS need IGF-I replacement treatment throughout life.
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PMID:Consequences of not treating children with laron syndrome (primary growth hormone insensitivity). 1196 19

Recently we found that interleukin-6 (IL-6) knockout mice develop mature-onset obesity and that a single intracerebroventricular (ICV) injection of IL-6 increases energy expenditure. In the present study we investigated if chronic ICV treatment with IL-6 can suppress body fat mass. IL-6 was injected ICV daily for two weeks to rats fed a high-fat diet. IL-6 treatment but not saline treatment decreased body weight by 8.4% and decreased the relative weights of mesenteric and retroperitoneal fat pads. Consistent with this, circulating leptin levels were decreased by 40% after IL-6 treatment but not after saline treatment. Average food intake per day was decreased in the IL-6 treated group compared to the saline treated rats. IL-6 treatment did not change hepatic expression of the acute-phase protein haptoglobin, serum levels of insulin or insulin-like growth factor-I, or the weights of the heart, liver, kidneys, adrenals, and spleen. We conclude that centrally administered IL-6 can decrease body fat in rats without causing acute-phase reaction.
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PMID:Intracerebroventricular interleukin-6 treatment decreases body fat in rats. 1205 38

The recent "obesity epidemic" among children and adolescents is a major public health concern. The mechanisms responsible for the increased incidence of childhood obesity are not yet well understood. The absence of a clear mechanism makes treating the obese child or adolescent a difficult task, and standardized therapeutic approaches simply do not yet exist. Metabolic derangements associated with obesity may contribute to the difficulty in treatment. Observed abnormalities in the growth hormone (GH)-insulin-like growth factor-I (IGF-I) axis in obese adults and the impact of exercise on the GH-IGF-I system are of particular relevance to the growing obese child. In this review, we focus on the interacting mechanisms of diet and exercise through specific hormonal mediators and their contribution to the current obesity epidemic. An improved understanding of these mechanisms may be helpful in creating effective treatment programs for children with obesity.
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PMID:Exercise, diet, and childhood obesity: the GH-IGF-I connection. 1209 90

Data on hormone replacement therapy and breast cancer risk come from a number of observational studies (mostly American studies). Those published up to 1995 were reanalyzed by the Collaborative Group on Hormonal Factors in Breast Cancer (CGHFBC). They involved populations where exceedingly high estrogen doses were used as first-line therapy, and a progestin was added in a minority of women. Overall, the CGHFBC reanalysis found that the relative risk increased by 0.023 for each year of use (with an absolute excess risk of two or six cases out of 1000 women treated for 5 or 10 years, respectively). Further American studies, published in 2000 and involving populations where lower doses were used, showed a risk increase of 0.01 per year of estrogen-only use. Both the CGHFBC reanalysis and the further studies did not find an increase of risk in treated overweight women. Possibly, overweight women already have a maximal estrogenic stimulus on the breast due to extraglandular estrogen production. An additional explanation could be that oral estrogens, through their hepatocellular effects, reverse some biological features of obesity (e.g. decreased sex hormone binding globulin level and increased insulin-like growth factor-I bioactivity) that potentially increase breast cancer risk, so balancing the estrogen stimulation. The CGHFBC reanalysis did not show a substantial difference in breast cancer risk between the majority using estrogen alone and the small minority using estrogen plus progestin. Conversely, Swedish studies and the recent American studies suggest that the risk increase could be higher with the addition of a progestin, compared with estrogen-only use. The biological effect of progesterone/progestins on the breast tissue is controversial. Even if the observed increase in risk could be partially ascribed to non-progesterone-like effects of some progestins (e.g. opposing the hepatocellular effects of oral estrogens) and also (in the American studies) to use-bias, a detrimental action due to progesterone-like effects cannot be excluded. However, the theoretical possibility exists that low doses of oral estrogens, plus a progestin providing progesterone-like effects only, will be shown to be associated with a limited breast cancer risk increase.
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PMID:Breast cancer and hormone replacement therapy: putting the risk into perspective. 1222 87

The aim of this study was to investigate whether the absence or presence of acne or hirsutism in 248 women with polycystic ovary syndrome was associated with different clinical, endocrine, metabolic and ultrasonographic factors. Patients were divided into three groups: 96 (38.7%) without any androgenic symptoms; 94 (37.9%) with only hirsutism; and 58 (23.4%) with only acne. The cycle alterations (oligomenorrhea or amenorrhea) and the echographic ovarian morphology (polycystic or multifollicular ovaries) showed no significant differences between the three groups. Hirsutism was associated with a greater incidence of obesity and insulin resistance, with an increase of 17-hydroxyprogesterone, ovarian and adrenal androgens, 3alpha-androstanediol glucuronide, insulin, insulin-like growth factor-I and low luteinizing hormone, sex hormone binding globulins and insulin-like growth factor binding protein-1 levels. Acne was associated only with the lowest 3alpha-androstanediol glucuronide levels. Therefore, two different pathogenetic mechanisms may play a role in the onset of acne and hirsutism.
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PMID:Acne and hirsutism in polycystic ovary syndrome: clinical, endocrine-metabolic and ultrasonographic differences. 1239 56

Obesity has a complicated relationship to both breast cancer risk and the clinical behavior of the established disease. In postmenopausal women, particularly the elderly, various measures of obesity have been positively associated with risk. However, before menopause increased body weight is inversely related to breast cancer risk. In both premenopausal and postmenopausal breast cancer, the mechanisms by which body weight and obesity affect risk have been related to estrogenic activity. Obesity has also been related to advanced disease at diagnosis and with a poor prognosis in both premenopausal and postmenopausal breast cancer. Breast cancer in African-American women, considering its relationship to obesity, exhibits some important differences from those described in white women, although the high prevalence of obesity in African-American women may contribute to the relatively poor prognosis compared with white American women. Despite the emphasis on estrogens to explain the effects of obesity on breast cancer, other factors may prove to be equally or more important, particularly as they relate to expression of an aggressive tumor phenotype. Among these, this review serves to stress insulin, insulin-like growth factor-I, and leptin, and their relationship to angiogenesis, and transcriptional factors.
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PMID:Breast cancer and obesity: an update. 1279 99

Uterine leiomyomas, or fibroids, represent a major public health problem. It is believed that these tumors develop in the majority of American women and become symptomatic in one-third of these women. They are the most frequent indication for hysterectomy in the United States. Although the initiator or initiators of fibroids are unknown, several predisposing factors have been identified, including age (late reproductive years), African-American ethnicity, nulliparity, and obesity. Nonrandom cytogenetic abnormalities have been found in about 40% of tumors examined. Estrogen and progesterone are recognized as promoters of tumor growth, and the potential role of environmental estrogens has only recently been explored. Growth factors with mitogenic activity, such as transforming growth factor- (subscript)3(/subscript), basic fibroblast growth factor, epidermal growth factor, and insulin-like growth factor-I, are elevated in fibroids and may be the effectors of estrogen and progesterone promotion. These data offer clues to the etiology and pathogenesis of this common condition, which we have analyzed and summarized in this review.
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PMID:Etiology and pathogenesis of uterine leiomyomas: a review. 1282 76


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