Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0028754 (obesity)
 124,988 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The granulin-epithelin precursor, progranulin, PC-cell-derived growth factor or acrogranin, is a high molecular weight secreted mitogen. It is abundantly expressed in rapidly cycling epithelial cells, in the immune system and in neurons, such as cerebellar Purkinje cells. Progranulin contributes to tumorigenesis in diverse cancers, including breast cancer, clear cell renal carcinoma, invasive ovarian carcinoma and glioblastoma. It regulates the rate of epithelial cell division in responsive epithelial cells, and confers an invasive phenotype on these cells. It is involved in the wound response. During embryogenesis, progranulin accelerates blastocyst formation, and is a growth factor for trophectodermal cells. In the neonate, progranulin, regulates the hormone-dependent virilization of the hypothalamus. It activates phosphorylation of Shc, and p44/42 MAPK (mitogen activated protein kinase) in the ERK (extracellular regulated kinase) signaling pathway; PI3K (phosophatidyl inositol-3-kinase), AKT/protein kinase B, and p70S6kinase in the phosophatidyl inositol-3-kinase pathway; and focal adhesion kinase in the adhesion/motility pathway. The signaling properties of progranulin are apparently similar to those of classic growth factors, but the functional properties of progranulin distinguish it from these molecules. Deleting the insulin-like growth factor I receptor from murine embryonic fibroblasts blocks proliferation in response to all classic growth factors, such as epidermal growth factor, or platelet-derived growth factor, whereas progranulin retains mitotic activity on these cells. The defined biological actions of progranulin probably represent a small fraction of its overall functions. Transcriptome analyses show that the progranulin gene is induced in numerous situations that vary from obesity to the transcriptional response of cells to antineoplastic drugs. Here, the biological roles of progranulin will be reviewed, with an emphasis on cancer and cell proliferation.
 ...
PMID:Progranulin (granulin-epithelin precursor, PC-cell derived growth factor, acrogranin) in proliferation and tumorigenesis. 1297 94

Expansion of adipose tissue mass results from increased number and size of adipocyte cells. We hypothesized that subcutaneous abdominal preadipocytes in obese individuals might have an intrinsically higher propensity to differentiate into adipocytes. Thus we investigated the relationship between obesity and the level of in vitro preadipocyte differentiation in Pima Indians. Subcutaneous abdominal stromal vascular fractions containing preadipocytes were cultured from 58 nondiabetic subjects [31 M/27 F, 30 +/- 6 yr, body fat 34 +/- 8% by dual-energy X-ray absorptiometry (means +/- SD)]. The average percentage of preadipocyte differentiation (PDIFF; cell count by microscopy) was 11 +/- 11% (range 0.2-51%). PDIFF correlated negatively with percent body fat (r = -0.35, P = 0.006) and waist circumference (r = -0.45, P = 0.0004). Multiple regression analysis indicated that waist circumference (P = 0.01), sex (P = 0.01), and percent body fat (P = 0.05) were significant determinants of PDIFF. Molecular characterization of predifferentiated cultured cells was performed by real-time PCR measurements of glucocorticoid receptor-alpha (GRalpha), insulin-like growth factor I receptor (IGF-IR), peroxisome proliferator-activated receptor-gamma (PPARgamma), enhancer-binding protein GATA-3, CCAAT/enhancer-binding protein-alpha undifferentiated protein (CUP/AP-2alpha), and endothelial cell-specific marker 2 (ECSM2). The mRNA concentrations of GRalpha correlated with PDIFF (r = 0.29, P = 0.03), but the others did not (IGF-IR, r = 0.003, P = 1.0; PPARgamma, r = -0.1, P = 0.5; GATA-3, r = 0.02, P = 0.9; CUP/AP-2alpha, r = -0.2, P = 0.1; ECSM2, r = 0.04, P = 0.7). Contrary to our hypothesis, the results may indicate a blunted in vitro differentiation potential of preadipocytes in centrally obese individuals. The lower differentiation potential of preadipocytes in the obese subjects might be due, at least partly, to decreased glucocorticoid receptor expression.
 ...
PMID:Subcutaneous abdominal preadipocyte differentiation in vitro inversely correlates with central obesity. 1497 8

Polycystic ovary syndrome is a common endocrine disorder in women. It is associated with hirsuitism, obesity, insulin resistance, abnormality in the growth hormone/insulin-like growth factor I (IGF-1) axis and polycystic ovaries. The etiology of PCOS has not been clarified. Ghrelin is an endogenous ligand of the growth hormone secretagogue receptor. It is mainly secreted by stomach cells but has also been shown to be present in hypothalamus, pituitary, pancreas and gonads. Ghrelin is a regulator of energy homeostasis and GH secretion. The influence of ghrelin on insulin secretion and gonadal function is known. Since ghrelin may play an important role in pathophysiology of PCOS, we studied ghrelin levels in a group of 52 women with PCOS and in 16 women in a control group. Plasma levels of insulin, total testosterone, SHBG, LH, and FSH were also measured. In conclusion, PCOS women have higher ghrelin levels than controls. Ghrelin negatively correlates with BMI and insulin levels in PCOS group. A relation between ghrelin and SHBG was observed. Our data suggest that ghrelin could be the possible link in PCOS etiology.
 ...
PMID:Elevated ghrelin plasma levels in patients with polycystic ovary syndrome. 1548 19

Mice with a fat-specific insulin receptor knock-out (FIRKO) have reduced adipose tissue mass, are protected against obesity, and have an extended life span. White adipose tissue of FIRKO mice is also characterized by a polarization into two major populations of adipocytes, one small (<50 microm) and one large (>100 microm), which differ with regard to basal triglyceride synthesis and lipolysis, as well as in the expression of fatty acid synthase, sterol regulatory element-binding protein 1c, and CCAAT/enhancer-binding protein alpha (C/EBP-alpha). Gene expression analysis using RNA isolated from large and small adipocytes of FIRKO and control (IR lox/lox) mice was performed on oligonucleotide microarrays. Of the 12,488 genes/expressed sequence tags represented, 111 genes were expressed differentially in the four populations of adipocytes at the p < 0.001 level. These alterations exhibited 10 defined patterns and occurred in response to two distinct regulatory effects. 63 genes were identified as changed in expression depending primarily upon adipocyte size, including C/EBP-alpha, C/EBP-delta, superoxide dismutase 3, and the platelet-derived growth factor receptor. 48 genes were regulated primarily by impairment of insulin signaling, including transforming growth factor beta, interferon gamma, insulin-like growth factor I receptor, activating transcription factor 3, aldehyde dehydrogenase 2, and protein kinase Cdelta. These data suggest an intrinsic heterogeneity of adipocytes with differences in gene expression related to adipocyte size and insulin signaling.
 ...
PMID:Intrinsic heterogeneity in adipose tissue of fat-specific insulin receptor knock-out mice is associated with differences in patterns of gene expression. 1513 Nov 19

The insulin-like growth factor I (IGF-I) generation test has the potential to assess the ability of an individual to respond to an acute bolus of growth hormone (GH), in terms of IGF-I, IGF-binding protein 3 and acid-labile subunit responses. This article will discuss something of the history of the IGF-I generation test, and review some of the major studies to date. The IGF-I generation test was first used in adults by Lieberman et al., who studied the effects of ageing and oestrogen administration, and suggested that decreased responsiveness to GH occurs with increasing age and oral oestrogen administration. Our results, however, show that, while activity of the GH/IGF-I axis declines with age, peripheral responsiveness to GH is not affected. As in the Lieberman study, we found that oral oestrogen replacement reduces responses of GH-dependent peptides to GH stimulation in healthy post-menopausal women. Transdermal oestrogen administration also reduced responsiveness to GH, although to a lesser degree than orally administered oestrogen. In addition, utilizing a non-weight-based dose of GH we have demonstrated that obese individuals produce greater increases in IGF-I following an acute bolus of GH. In GH deficiency (GHD), data suggesting enhanced peripheral responsiveness should be interpreted with caution, and with awareness of differences between these groups in terms of age and obesity. The IGF-I generation test may allow a fresh approach to unanswered questions in the field of GHD, but as the IGF-I response to GH is not strictly associated with protein anabolism or clinical benefit, the question remains whether this test will predict the effect of longer-term GH administration.
 ...
PMID:The insulin-like growth factor I generation test in adults. 1576 Dec 32

Visceral obesity in men has been reported to be characterized by low testosterone (T) and insulin-like growth factor I (IGF-I) concentrations, the latter suggesting a relative growth hormone (GH) deficiency. Since T and GH-secretions are interrelated, men with visceral obesity were substituted with T for 14 days, and diurnal secretion pattern of GH as well as IGF-I concentrations, and metabolic variables were followed. Visceral obese men were characterized by a decreased total GH secretion and diminished peak amplitude, size, and number. T-substitution was followed by elevation of IGF-I levels. The IGF-I increase correlated with the elevation of T-concentration, and was most pronounced in men with the lowest concentrations of free T from the outset. There were no detectable changes in total quantity, amplitude, size or number of peaks of GH secretion. Glucose, chlolesterol and triglycerides as well as diastolic blood pressure decreased. There were no changes in thyroid or hematology variables. T-substitution of visceral obese men is followed by an elevation of IGF-I concentrations. It is suggested that this might be due either to minor, non-detectable increases in GH secretion, or to direct effects of T on IGF-I concentrations. The regulatory mechanisms by which T-administration are leading to metabolic and anthropometric improvements, might be direct effects of T, with or without mediation via GH secretion.
 ...
PMID:Growth hormone secretion after testosterone administration to men with visceral obesity. 1635 27

Laron syndrome (LS) is an autosomal recessive disease caused by deletions or mutations in the GH receptor gene leading to an inability of insulin-like growth factor I (IGF-I) generation. Among the major resulting body changes are dwarfism and obesity. The only effective treatment is daily administration of biosynthetic IGF-I. Body composition determination by DEXA (dual energy X-ray absorptiometry) of three girls with LS treated by IGF-I for 1, 3 and 11 1/2 years, respectively, revealed that concomitantly with the increase in growth there was a significant increase in body adipose tissue to double or triple the normal values. Due to the underdevelopment of the muscular and skeletal systems body mass index (BMI) did not accurately reflect the degree of obesity. In conclusion, IGF-I similar to insulin, exerts an adipogenic effect.
 ...
PMID:Long-term IGF-I treatment of children with Laron syndrome increases adiposity. 1644 22

Epidemiologic evidence suggests obese premenopausal women experience a reduced risk of breast cancer. The mechanism underlying this protection is not fully understood although it is well documented that abdominal obesity may impair ovulatory function and reduce gonadal steroidogenesis. We measured levels of several metabolic markers that are modified by obesity [measured by body mass index (BMI, (weight (kg)/height (m2)))] and play a role in the reproductive axis, including, leptin, insulin-like growth factor I (IGF-I), insulin-like growth factor binding protein 3 (IGFBP3), C-peptide and prolactin in 233 cases and 251 controls participating in a retrospective study of breast cancer in young women conducted in the Seattle/Puget Sound region between 1990 and 1992. Consistent with the finding of a reduced risk with increasing BMI, risks declined with leptin levels, although to a lesser degree with odds ratios (OR) for the highest vs. lowest quartile of BMI=0.34 (95% C.I. 0.3-0.8) and for leptin=0.71 (95% C.I. 0.5-1.3). IGF-I, IGFBP3, C-peptide and prolactin were not related to breast cancer risk in a dose-dependent manner. With the possible exception of leptin, our findings do not suggest that these markers explain the breast cancer protection provided by obesity in premenopausal women.
 ...
PMID:Interrelationships between serum leptin, IGF-1, IGFBP3, C-peptide and prolactin and breast cancer risk in young women. 1650 16

The aim of the present study was to evaluate the mediating role played by obesity on the relationship of free insulin-like growth factor I (IGF-I) and IGF-binding protein-3 (IGFBP-3) with muscle strength and physical performance. Data were from baseline evaluation of the ilSIRENTE Study. Muscle strength was measured by hand grip strength. Physical performance was assessed using the walking speed and the 0-3 Short Physical Performance Battery (SPPB) score. Based on its median value, free IGF-I was categorized in the following two groups: low IGF-I (IGF-I <0.65 ng/ml; n = 174) and high IGF-I (IGF-I > or =0.65 ng/ml; n = 175). Similarly, IGFBP-3 was categorized in the following two groups: low IGFBP-3 (IGFBP-3 <4,319.9 ng/ml; n = 174) and high IGFBP-3 (IGFBP-3 > or =4,319.9 ng/ml; n = 175). Body mass index (BMI) was categorized as follows: <25 kg/m(2) (n = 160), 25-29.9 kg/m(2) (n = 133), > or =30 kg/m(2) (n = 56). Mean age of the 349 participants was 85.8 yr, and 234 (67%) were women. After adjusting for potential confounders, no significant association of IGF-I and IGFBP-3 with study outcomes was observed. After the study sample was stratified by BMI groups, compared with participants with low IGF-I level, those with high IGF-I level had a significantly better grip strength [35.2 +/- 1.6 vs. 29.2 +/- 2.0 (SE) kg, P = 0.03], walking speed (0.55 +/- 0.04 vs. 0.40 +/- 0.04 m/s, P = 0.01), and SPPB score (1.9 +/- 0.1 vs. 1.5 +/- 0.1 m/s, P = 0.01) but only in the group with BMI > or =30 kg/m(2) and not in other BMI groups. A statistically significant interaction between BMI and IGF-I level was observed on all study outcomes. By contrast, no association was observed between IGFBP-3 and study outcomes, independently of BMI. In conclusion, high IGF-I level is associated with better physical function in older persons with obesity, but not in nonobese subjects.
 ...
PMID:Body mass index, free insulin-like growth factor I, and physical function among older adults: results from the ilSIRENTE study. 1668 49

Nutrition is an important regulator of the tempo of growth and obesity is usually associated with tall childhood stature and earlier pubertal development. Several longitudinal studies have demonstrated that timing of puberty is most closely linked to infancy weight gain: suggesting an early window for programming of growth and development. Earlier puberty in the UK MRC 1946 birth cohort was related to smaller size at birth and rapid growth between 0 and 2 years. Rapid early weight gain leads to taller childhood stature and higher insulin-like growth factor I (IGF-I) levels, possibly through early induction of growth hormone (GH) receptor numbers, and such children are also at risk of childhood obesity. In the Avon Longitudinal Study of Parents and Children, rapid infancy weight gain was associated with increased risk of obesity at 5 and 8 years, with evidence of insulin resistance, exaggerated adrenarche and reduced levels of sex hormone binding globulin (SHBG). Potentially the elevated IGF-I and adrenal androgen levels, increased aromatase activity and increased 'free' sex steroid levels consequent to lower SHBG levels could all promote activity of the GnRH pulse generator. In addition obese children have higher leptin levels, a proven permissive factor in initiating LH pulsatility. Obesity could also affect the rate of progression through puberty as nutrition and SHBG may act respectively as an accelerator and brake on peripheral sex steroid action. Early weight gain and early pubertal development might also be associated with loss of the pubertal growth spurt perhaps through obesity-related suppression of GH secretion. Trans-generational recurrence of low birth weight, early catch-up weight gain, earlier menarche, and shorter adult stature have been observed in women, and could contribute to the strong heritability in age at menarche.
 ...
PMID:Early and late weight gain and the timing of puberty. 1682 79


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>