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

This chapter summarises the results of a recent study which investigated the role of the hypothalamo-pituitary relay system in mediating the effects of photoperiod on seasonal cycles in: (a) body weight; (b) pelage growth; and (c) reproduction in Soay rams. Hypothalamo-pituitary disconnected (HPD) and the control rams were housed indoors under an artificial lighting regimen of alternating 16-weekly periods. These periods consisted of long (16L:8D) and short days (8L:16D) and lasted for more than 2 years. The: (i) body weight; (ii) voluntary food intake; (iii) pelage and horn growth; and (iv) variations in testicular diameter were measured routinely every 2-4 weeks. Twice-weekly blood samples were collected to monitor long-term changes in the blood concentrations of: (1) pituitary; (2) metabolic; and (3) reproductive hormones (prolactin, GH, alpha-MSH, beta-endorphin, ACTH, TSH, LH, FSH, cortisol, insulin, IGF1 and testosterone). In control rams there were clearly defined photoperiod-induced cycles in blood concentrations of prolactin, alpha-MSH, beta-endorphin, LH, FSH, insulin and testosterone and associated morphological changes consistent with causal relationships (e.g. prolactin versus wool and horn growth, alpha-MSH, beta-endorphin and insulin versus body weight/food intake, LH and FSH versus testis size). In the HPD rams there were no photoperiod-induced cycles in the concentrations of any of the pituitary hormones with the exception of prolactin which varied as in controls (10-fold higher under long days). There was a permanent increase in blood concentrations of alpha-MSH, beta-endorphin and insulin in the HPD animals and a decrease in the concentrations of GH (loss of pulsatility) and IGF1. These changes were associated with the development of obesity. The reproductive axis was inactivated (basal LH, FSH and testosterone) although there was residual cyclicity in the size of the testis associated with the changes in prolactin secretion. Overall, the results support the view that the melatonin signal which encodes photoperiod, acts in the hypothalamus to regulate some photoperiodic responses (alpha-MSH and beta-endorphin-body weight axis, gonadotrophin-gonadal axis) but acts in the pituitary gland to regulate other responses (prolactin-pelage axis). However, a functional hypothalamus is required to generate normal seasonal cycles in: (a) body weight; (b) food intake; (c) growth; (d) fattening; and (e) reproduction, to provide the internal coordination between different systems and to facilitate the temporal entrainment to environmental cues.
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PMID:Photo-neuroendocrine control of seasonal cycles in body weight, pelage growth and reproduction: lessons from the HPD sheep model. 982 1

Present knowledge on the effects of growth hormone (GH)/insulin-like growth hormone (IGF)1 deficiency on ageing and lifespan are reviewed. Evidence is presented that isolated GH deficiency (IGHD), multiple pituitary hormone deficiencies (MPHD) including GH, as well as primary IGE1 deficiency (GH resistance, Laron syndrome) present signs of early ageing such as thin and wrinkled skin, obesity, hyperglycemia and osteoporosis. These changes do not seem to affect the lifespan, as patients reach old age. Animal models of genetic MPHD (Ames and Snell mice) and GH receptor knockout mice (primary IGF1 deficiency) also have a statistically significant higher longevity compared to normal controls. On the contrary, mice transgenic for GH and acromegalic patients secreting large amounts of GH have premature death. In conclusion longstanding GH/IGF1 deficiency affects several parameters of the ageing process without impairing lifespan, and as shown in animal models prolongs longevity. In contrast high GH/IGF1 levels accelerate death.
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PMID:Effects of growth hormone and insulin-like growth factor 1 deficiency on ageing and longevity. 1185 84

We have evaluated the possible association of polycystic ovary syndrome (PCOS) with 15 genomic variants previously described to influence insulin resistance, obesity, and/or type 2 diabetes mellitus. Seventy-two PCOS patients and 42 healthy controls were genotyped for 15 variants in the genes encoding for paraoxonase (three variants), plasma cell differentiation antigen glycoprotein, human sorbin and SH3 domain containing 1, plasminogen activator inhibitor-1, peroxisome proliferator-activated receptor-gamma2, protein tyrosine phosphatase 1B (two variants), adiponectin (two variants), IGF1, IGF2, IGF1 receptor, and IGF2 receptor. Compared with controls, PCOS patients were more frequently homozygous for the -108T variant in paraoxonase (36.6% vs. 9.5%; P = 0.002) and homozygous for G alleles of the ApaI variant in IGF2 (62.9% vs. 38.1%; P = 0.018). Paraoxonase is a serum antioxidant enzyme and, because -108T alleles result in decreased paraoxonase expression, this increase in oxidative stress might result in insulin resistance. G alleles of the ApaI variant in IGF2 may increase IGF2 expression, and IGF2 stimulates adrenal and ovarian androgen secretion. In conclusion, the paraoxonase -108 C-->T variant and the ApaI polymorphism in the IGF2 gene are associated with PCOS and might contribute to increased oxidative stress, insulin resistance, and hyperandrogenism in this prevalent disorder.
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PMID:Association of the polycystic ovary syndrome with genomic variants related to insulin resistance, type 2 diabetes mellitus, and obesity. 1518 Oct 35

Energy balance, or the ability to maintain body weight by balancing energy intake with energy expenditure, appears to be important in the etiology of colon cancer. One possible mechanism whereby energy balance may be associated with colorectal cancer is through its association with insulin. In our study, we evaluate the interaction between polymorphisms in 4 genes thought to be involved in insulin-related functions and components of energy balance with risk of colorectal cancer. Data from 2 population-based case-control studies of colon and rectal cancer conducted in Utah and Northern California were used to evaluate associations between body mass index (BMI), physical activity, energy intake and sucrose-to-fiber ratio and a CA repeat polymorphism of the IGF1 gene, the A/C polymorphism at nucleotide -202 of the IGFBP3, the G972R polymorphism of the IRS1 gene and the G1057D polymorphism of the IRS2 gene. A total of 1,346 incident colon cancer cases and 1,544 population-based controls and 952 incident rectal cancer cases and 1,205 controls were available for analysis. Inconsistent associations were identified between BMI, physical activity, energy intake and insulin-related genes. The 192/192 IGF1 genotype was associated with significant reduction in colon cancer risk among those with high physical activity (odds ratio [OR] 0.57; 95% confidence interval [CI] 0.39-0.83; p interaction 0.01). Although there was no significant pattern of interaction between either BMI or energy intake and polymorphisms assessed, specific sources of energy did appear to be more related to colon cancer risk in the presence of specific IRS2 and IGF1 genotypes. A high sucrose-to-fiber ratio increased risk of colon cancer in men who had the IRS2 DD genotype and among men who did not have the 192/192 IGF1 genotype. In summary, these data support the importance of components of energy balance in risk of colorectal cancer. Obesity, physical activity and energy intake appear to alter risk of colorectal cancer; however, the risk appears to be minimally influenced by genetic variants evaluated.
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PMID:Energy balance, insulin-related genes and risk of colon and rectal cancer. 1568 7

The contribution of leptin, as a possible link between osteoarthritis (OA) and obesity, was studied in cartilage and synovial fluid samples obtained from osteoarthritic patients. Its effect on cartilage was evaluated in rats after intraarticular injections of leptin. Leptin levels were measured in the synovial fluid samples by enzyme linked immunosorbent assay; leptin concentrations were correlated with the body mass index. Leptin was strongly expressed in osteophytes and OA cartilage, while, in normal cartilage, few chondrocytes produced leptin. The level of leptin expression was related to the grade of cartilage destruction and was in good relation with those of growth factors as IGF1 and TGFb. Studies in rats showed that intraarticular leptin injection stimulated anabolic functions of chondrocytes and induced the synthesis of leptin, IGF1 and TGFB in cartilage at both the chondrocytes and induced the synthesis of leptin, IGF1 and TGFB in cartilage at both the mRNA and protein levels. In conclusion, leptin may be a link between osteoarthritis and obesity, and may play a key role in cartilage metabolism. Leptin may contribute to the pathophysiology of OA.
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PMID:[Is leptin the missing link between osteoarthritis and obesity?]. 1597 87

Polymorphisms affecting insulin-like growth factors (IGF), their binding proteins (IGFBP), insulin receptor substrates (IRS), and other IGF regulatory molecules may affect growth, obesity, and obesity-related diseases, including cancer. The objective of this study was to better describe the associations between several IGF pathway variants and body size. Hispanic (n = 462) and non-Hispanic White (n = 1,702) women were recruited as controls in collaborative population-based case-control studies in Arizona, New Mexico, Colorado, Utah, and California. Body size measurements were taken by trained interviewers; genotypes were determined for the IGF1 CA repeat, the IGFBP3 -202 C > A substitution, the IRS1 G972R and IRS2 G1057D substitutions, and the vitamin D receptor (VDR) BsmI and FokI polymorphisms. Two associations were observed that were consistent in both Hispanics and non-Hispanic Whites: IGF1 CA repeat alleles of length other than 19 were associated with higher mean waist-to-hip ratios (WHR), P = 0.01, and women who carried an IGFBP3 A allele, compared with women with the CC genotype, more often reported high birthweight (odds ratio, 1.9; 95% confidence interval, 1.1-3.2). We observed trends for associations between IGFBP3 A allele and taller height, IRS1R allele, and smaller WHR, and VDR FokI ff genotype and larger WHR; each of these trends was present in only one ethnic group, and heterogeneity of effect by ethnicity was detected. These results provide evidence that IGF pathway polymorphisms have functional effects on growth and central obesity and indicate that genotype-phenotype relationships are ethnic specific.
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PMID:Insulin-like growth factor pathway polymorphisms associated with body size in Hispanic and non-Hispanic white women. 1603 Jan 20

Polycystic ovary syndrome (PCOS) is a common heterogenous endocrine disorder associated with amenorrhoea (or oligomenorrhoea), hyperandrogenism, hirsutism, obesity, insulin resistance, and an approximately 7-fold increased risk of type 2 diabetes mellitus (NIDDM - non-insulin dependent diabetes mellitus). It is a leading cause of female infertility. The prevalence of PCOS among reproductive-age women has been estimated at 4%-12%. Familial aggregation of this syndrome is well established. There are also ethnic and racial variations in the prevalence of the syndrome and its symptoms. Multiple biochemical pathways have been implicated in the pathogenesis of PCOS. Several genes from these pathways have been tested include genes involved in steroid hormone biosynthesis and metabolism (StAR, CYP11, CYP17, CYP19 HSD17B1-3, HSD3B1-2), gonadotropin and gonadal hormones action (ACTR1, ACTR2A-B, FS, INHA, INHBA-B, INHC, SHBG, LHCGR, FSHR, MADH4, AR), obesity and energy regulation (MC4R, OB, OBR, POMC, UCP2-3), insulin secretion and action (IGF1, IGF1R, IGFBPI1-3, INS VNTR, IR, INSL, IRS1-2, PPARG) and many others. Most women with PCOS, both obese and lean, have a degree of insulin resistance. The minisatellite of insulin gene (INS VNTR), especially class III alleles and III/III genotypes might not only determine the predisposition to anovulatory PCOS but also the concomitant risk for development of type 2 diabetes. The function of the insulin receptor (IR) is probably normal in woman with PCOS. However abnormal serine phosphorylation in the receptor may impair signal transduction accounting for a post-binding defect in insulin action. Serine phosphorylation is also involved in the postranslational regulation of 17,20-lyase activity (CYP17). There may be a common aetiology for both insulin resistance and hyperandrogenism. Polymorphic alleles of both IRS-1 and IRS-2 (insulin receptor substrate 1 - 2), alone or in combination, may have a functional impact on the insulin-resistant component of PCOS. There is no evidence to suggest that follistatin gene polymorphisms play a role in the pathogenesis of insulin resistance in PCOS women. PCOS appears to be associated with the absence of the four-repeat-units allele in a polymorphic region of pentanucleotide (TTTTA)n repeats within CYP11A gene, which encodes cytochrome P450scc. It has been hypothesized that up-regulation of this enzyme could lead to increased androgen production. There is no evidence of any association of alleles of CYP19 gene (encoding cytochrome P450arom) with PCOS. Association exists between androgen receptor gene (AR) polymorphisms an androgens action in PCOS. Increased hirustism and decreased CAG repeat length within AR gene has been also demonstrated in women with normal testosterone levels. Expression of estrogen receptor (ERs) as well as 5-alpha-reeducates (SRD5A1-2 genes) activity was analysed in granulosa (GC) and theca cells (TC). The results of this study demonstrate that there are significant alterations in the expression of ERalpha and ERbeta in PCOS that may be related to abnormal follicular development. On the other hand elevated SRD5A activity in polycystic ovaries supported the hypothesis that 5-alpha-reduced androgens may play a role in the pathogenesis of the syndrome. The genetic aetiology of PCOS remains unknown. There are a number of interlinking factors that affects expression of PCOS. Single cause of PCOS is unlikely. Other possible mechanisms in pathogenesis of PCOS are discussed.
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PMID:[Genetic aspects of polycystic ovary syndrome]. 1635 Jul 21

We hypothesize that the peroxisome proliferator-activated receptor-gamma (PPARgamma) is associated with colorectal cancer given its association with insulin, diabetes, obesity, and inflammation. In this study, we evaluated the association between colorectal cancer and specific tumor mutations and the Pro12Ala (P12A) PPARgamma polymorphism. We also evaluated interactions between the PPARgamma gene and other insulin-related genes and use of aspirin and non-steroidal anti-inflammatory drug use. Data were available from 1,577 cases of colon cancer that were matched to 1,971 population-based controls and 794 cases of rectal cancer that were matched to 1,001 population-based controls. Colon tumors from the case subjects were evaluated for p53 and Ki-ras mutations and microsatellite instability (MSI). Insulin-related genes evaluated were the Bsm1, polyA, and Fok1 polymorphisms of the VDR gene; the G972R IRS1 polymorphism; the G1057D IRS2 polymorphism; the 19CA repeat polymorphism of the IGF1 gene; and the -200A>C IGFBP3 polymorphism. The odds ratio (OR) between the PA/AA genotypes and proximal tumors was 0.83 (95% CI: 0.69-1.01); for distal tumors was 1.00 (95% CI: 0.83-1.21); and for rectal tumors was 1.04 (95% CI: 0.86-1.25). Evaluation of specific types of tumor mutations showed that colon cancer cases with the PA or AA genotypes were less likely to have p53 tumor mutations (OR 0.78; 95% CI: 0.62-0.99), specifically transition mutations (OR 0.74; 95% CI: 0.56-0.97). Colon cancer cases also were less likely to have a tumor with MSI if they had the PA or AA PPARgamma genotype (OR 0.68; 95% CI: 0.47-0.98); differences in Ki-ras mutations were not seen in colon tumors by PPARgamma genotype. Those who did not take ibuprofen-type drugs and had the PA or AA genotypes were at a significantly greater risk of rectal cancer (OR 2.11; 95% CI: 1.52-2.92; p interaction 0.03) than people with the PP genotype regardless of ibuprofen-type drug use. There was a significant interaction between the -200A>C IGFBP3 polymorphism and the Pro12Ala PPARgamma polymorphism and risk of colon cancer (p for interaction = 0.02) with individuals being at significantly lower risk if they had both the CC IGFBP3 genotype and the PA/AA PPARgamma genotype. For rectal cancer there was a significant interaction between the Bsm1/polyA polymorphisms (p = 0.001) of the VDR gene and the PA/AA Pro12Ala PPARgamma polymorphism with the highest risk group being those with both the PA/AA Pro12Ala PPARgamma and the BB/SS VDR genotypes. These data suggest that PPARgamma may be associated with many aspects of colorectal cancer including insulin- and inflammation-related mechanisms.
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PMID:PPARgamma and colon and rectal cancer: associations with specific tumor mutations, aspirin, ibuprofen and insulin-related genes (United States). 1648 31

Despite enormous medical progress during the past few decades, the last years of life are still accompanied by increasing ill health and disability. The ability to maintain active and independent living for as long as possible is a crucial factor for ageing healthily and with dignity. The most important and drastic gender differences in aging are related to the reproductive organs. In distinction to the course of reproductive ageing in women, with the rapid decline in sex hormones expressed by the cessation of menses, men experience a slow and continuous decline. This decline in endocrine function involves: a decrease of testosterone, dehydro epiandrosterone (DHEA), oestrogens, thyroid stimulating hormone (TSH), growth hormone (GH), IGF1, and melatonin. The decrease of sex hormones is concomitant with a temporary increase of luteinizing hormone (LH) and follicle-stimulating hormone (FSH). In addition sex hormone binding globulins (SHBG) increase with age resulting in further lowering the concentrations of free biologically active androgens. These hormonal changes are directly or indirectly associated with changes in body constitution, fat distribution (visceral obesity), muscle weakness, osteopenia, osteoporosis, urinary incontinence, loss of cognitive functioning, reduction in well being, depression, as well as sexual dysfunction. The laboratory and clinical findings of partial endocrine deficiencies in the aging male will be described and discussed in detail. With the prolongation of life expectancy both women and men today live 1/3 of their life with endocrine deficiencies. Interventions such as hormone replacement therapy may alleviate the debilitating conditions of secondary partial endocrine deficiencies by preventing the preventable and delaying the inevitable.
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PMID:Endocrinology of the aging male. 1658 70

Obesity is associated with insulin resistance in skeletal muscle; accordingly, weight loss dramatically improves insulin action. We sought to identify molecular remodeling of muscle commensurate with weight loss that could explain improvements in insulin action. Muscle from morbidly obese women was studied before and after gastric bypass surgery. Gastric bypass surgery significantly reduced body mass by approximately 45% and improved insulin action. We then assessed mRNA profiles using a stringent statistical analysis (statistical concordance with three probe set algorithms), with validation in a cross-sectional study of lean (n = 8) vs. morbidly obese (n = 8) muscle. Growth factor receptor-bound protein 14 (GRB14), glycerol-3-phosphate dehydrogenase 1 (GPD1), and growth differentiation factor 8 (GDF8; myostatin) significantly decreased approximately 2.4-, 2.2-, and 2.4-fold, respectively, after weight loss (gastric bypass). Increased expression of these transcripts was associated with increased obesity in the cross-sectional group (lean vs. morbidly obese muscle). Each transcript was validated by real-time quantitative RT-PCR assays in both study groups. Using Ingenuity Pathway Analysis, we show that all three transcripts are involved in the same regulatory network including AKT1, IGF1, TNF, PPARG, and INS. These results suggest that GRB14, GPD1, and GDF8 are weight loss-responsive genes in skeletal muscle and that the observed transcriptional modulation of these would be expected to improve insulin signaling, decrease triglyceride synthesis, and increase muscle mass, respectively, with weight loss. Thus our data provide a possible regulatory pathway involved in the development of insulin resistance in the morbidly obese state, and improvement of insulin resistance with weight loss.
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PMID:GRB14, GPD1, and GDF8 as potential network collaborators in weight loss-induced improvements in insulin action in human skeletal muscle. 1684 34


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