Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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

In Basle in 1972 a diabetes survey was performed in subjects with increased risk of diabetes mellitus (overweight, age above 50, relatives of diabetics). For screening, the blood sugar was determined one hour after ingestion of 50 g of glucose. 404 males and 768 females (known diabetics excluded) were examined. One third of males and one quarter of females had a blood sugar value above 150 mg%. Blood sugar values of more than 200 mg% were found in 9% of the male and 7% of the female participants. A positive correlation existed between age and blood sugar values in males and females. Body weight and blood sugar value correlated only in females. However, in male subjects with pronounced obesity (Broca index greater than 1.23) there was a significantly higher incidence of blood sugar screening value above 150 mg% than in the rest of the males. It would appear that even slight overweight enhances glucose intolerance in females, whereas in males only marked overweight favours the manifestation of glucose intolerance. The cost of the detection of a new case of diabetes mellitus (blood sugar greater than 200 mg%) amounted to Sfr. 70.-. The Basle diabetes survey provides a model for successful conduct of a preventive program through cooperation of private organizations such as the local Medical Association and the local Diabetes Association.
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PMID:[Procedures for the early recognition of diabetics in Basle 1972. Contributions to the early diagnosis of diabetes mellitus by means of blood sugar analysis with special reference to the practical procedures under Swiss conditions]. 125 14

We investigated the influence of the diabetic state on the contractile response of longitudinal segments of isolated mesenteric vein to prostanoids and leukotriene (LT), and the contribution of the vascular endothelium to modulation of the contractile response was determined. The normal mesenteric vein and de-endothelialized veins of normal (ddY), diabetic KK-CAy and streptozotocin ddY mice (150 mg/kg, i.v., 6 weeks) were used. In the diabetic state, the contractions produced by noradrenaline (60 microM), high K+ solution (143.4 mM), and the thromboxane A2 analogue U-46619 (29 nM-29 mM) were not affected, and LTD4 (0.1 nM-1 microM)-induced contraction was suppressed. Contractions induced by prostaglandin (PG) E2 (0.2 microM-2 mM), PGF2 alpha (0.3 microM-0.3 mM) and the prostacyclin derivatives PGI2-Na (10-100 microM) and TRK-100 (0.2 microM-2 mM) were significantly enhanced in the presence of an intact vascular endothelium, but not in de-endothelialized segments. The increase in PGF2 alpha (0.28 mM) contractions was dependent on age (correlation coefficient r = 0.36, significant difference, P less than 0.05) and blood glucose (r = 0.88, significant difference, P less than 0.01), but was independent of obesity. The contractile response to PGD2 (0.3-0.9 mM) was enhanced in both intact and de-endothelialized segments. These results indicate that the diabetic state affects prostanoid responses in an endothelium-dependent manner, except for the PGD2 response, which is independent of the endothelium.
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PMID:Diabetes-induced enhancement of prostanoid-stimulated contraction in mesenteric veins of mice. 262 93

The role of dietary fat and fiber in energy restriction for the management of obesity was examined. Twelve male castrated dogs were energy restricted for 7 weeks by feeding 60% of their calculated maintenance energy requirements (MER = 1500 kcal/m2/d) for ideal body weight. Six dogs were restricted on a high-fat (35.4 kcal% from fat), low-fiber (2.9% dry matter basis [DMB]) diet while the other six dogs were restricted on a low-fat (24.5 kcal% from fat), high-fiber (27% DMB) diet. Compared with the high-fat, low-fiber diet, energy restriction on the low-fat, high-fiber diet resulted in significantly greater decreases in body fat (1472 +/- 166 vs. 853 +/- 176 g; p < 0.05) and total serum cholesterol concentrations (108.7 +/- 11.3 vs. 51.5 +/- 13.9 mg/dL; p < 0.005). Reductions in body weight (2.86 +/- 0.3 vs. 2.14 +/- 0.3 kg; p < 0.09), and mean arterial blood pressure (17.4 +/- 6.1 vs. 6.7 +/- 2.9 mmHg; p < 0.12) were also greater on the low-fat diet; however, these diet effects did not reach statistical significance. These data suggest that the fat and fiber content of the diet during energy restriction are important factors in the management of obesity.
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PMID:Differential metabolic effects of energy restriction in dogs using diets varying in fat and fiber content. 882 58

It has been suggested that television watching and physical activity are related to obesity. This association, however, has been investigated mainly in children. This study provided the opportunity to examine the relationship between television watching, physical activity, and body mass index in adult Pima Indians, a population with a high prevalence of obesity. Hours per day of television watched, past-year physical levels (MET-h/wk; leisure and occupational combined) and BMI (kg.m-2) were measured in 2452 men and women subjects 21-59 yr old. In adults between the ages of 21 and 39 yr, TV and physical activity levels were negatively correlated (r = -0.11 for men and -0.10 for women). Weaker associations were found between TV and BMI (r = 0.08 for men and 0.04 for women). There were no significant relationships among these variables in older adults (49-59 yr), possibly because of low reported levels of physical activity and TV. Multiple linear regression analysis revealed that physical activity and television watching in men and activity in women were significantly related to BMI. These data suggest that increasing activity levels and decreasing the time spent in sedentary behavior such as watching television should both be considered as potential intervention strategies in obesity prevention programs.
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PMID:Associations among physical activity, television watching, and obesity in adult Pima Indians. 924 90

Gonadotropin-releasing hormone (GnRH) is a key hypothalamic peptide that controls the secretion of pituitary gonadotropins, particularly luteinizing hormone (LH), and hence gonadal function. Hypothalamic GnRH is released in a pulsatile manner. In the female, the pattern of GnRH pulses, i.e., pulse frequency and amplitude, varies during different reproductive stages and among different species. Several central and peripheral signals modulate GnRH neuronal activities. Some of these signals are stimulatory to GnRH release, e.g., norepinephrine (NE) and neuropeptide Y (NPY); some are inhibitory, e.g., beta-endorphin and interleukin-1; others are both stimulatory and inhibitory, e.g., estradiol-17 beta (E2). The neuronal structures and chemical interactions that result in pulsatile GnRH release remain unresolved. However, the core of the so-called 'GnRH pulse-generator' likely involves NE and NE transporter (NET, the protein for pre-synaptic re-uptake of NE). Both secretion and re-uptake of NE may determine hypothalamic NE availability. Many of the GnRH-stimulating and GnRH-inhibiting signals may influence the 'pulse-generator' by acting on GnRH neurons as second level signals. Hypothalamic GnRH is also released in a "surge" manner that is triggered either by increasing levels of circulating steroids (E2 and progesterone) during the preovulatory period in spontaneous-ovulating species, or by coitus in induced-ovulating animals. The sequential steps and mechanisms by which the GnRH surge occurs after E2 or coitus are not clear. However, it is unlikely that the E2 or coital stimuli act directly on GnRH neurons; E2 receptors have not been found in GnRH cells whereas coital signals must stop in the brainstem before they reach the hypothalamus. The brainstem may be an extra-hypothalamic site where both E2 and coital stimuli are transformed into GnRH-stimulating signals. One such signal may be NE whose brainstem cell bodies send terminals into the hypothalamus. Evidence from our laboratory suggests that a hypothalamic NE surge occurs at the time of the preovulatory GnRH surge in both the monkey and rabbit. Moreover, gene expression of both tyrosine hydroxylase (the rate-limiting enzyme for NE synthesis) and NET (the rate-limiting factor for synaptic NE transmission) in the brainstem increases after E2 in the monkey and after coitus in the rabbit. Other hypothalamic and/or brainstem signals, i.e., NPY, galanin, beta-endorphin, nitrous oxide and gamma aminobutyric acid, are likely involved in generating, maintaining and/or modulating the GnRH surge process. A better understanding of the up-stream GnRH-regulating signals will help improve treatments for many reproductive disorders associated with stress, obesity, infection and aging.
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PMID:Neuroendocrine signals in the regulation of gonadotropin-releasing hormone secretion. 955 Dec 47

Dietary treatment of pediatric obesity is a challenge given the need for adequate nutrients to support the maintenance of lean tissue and growth. The primary purpose of this investigation was to assess the effects of reduced energy intake on protein turnover in obese children aged 8 to 10 years. Following a 2-week baseline period, 16 subjects reduced energy intake during a 6-week intervention period. At baseline and following the intervention, 15N-glycine methodology was used to measure nitrogen flux (Q), protein synthesis (PS), protein breakdown (PB), and net turnover ([NET] PS - PB). Other criterion measures included resting metabolic rate (RMR), fat mass (FM), fat-free mass (FFM), urinary creatinine to height ratio (Cr:Ht), and nitrogen balance (NB). On average, subjects lost 2.2 +/- 0.3 kg, of which greater than 85% was FM. Decreased Q (P = .03) indicated downregulation of protein turnover in response to diet-induced weight loss. While PB did not change, NET declined slightly (P = .06) as a consequence of reduced PS (P = .03). Reductions in FFM (P = .09), Cr:Ht (P = .02), and NB (P = .03) accompanied alterations in protein turnover, but there was no change in the RMR. In conclusion, while short-term therapy promoted the loss of FM and did not compromise RMR, practitioners must be cautious when prescribing diets, given the observed changes in protein utilization and somatic protein status. Longitudinal studies are needed to further characterize the metabolic responses of obese children to long-term diet therapy.
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PMID:Effects of reduced energy intake on protein utilization in obese children. 986 70

We previously demonstrated that taste receptor cells (TRCs) respond to cis-polyunsaturated fatty acids (PUFAs) through an inhibition of delayed rectifying K channels (KDR), which may represent the transduction mechanism for dietary fat. To determine if there is a link between the sensitivity of fungiform TRCs to PUFAs and dietary fat preferences, we compared the PUFA-sensitivity of TRCs using patch clamp techniques from Osborne-Mendel (O-M) and S5B/Pl rats, which display dietary preferences for fat over carbohydrate and carbohydrate over fat, respectively. In isolated TRCs, the PUFAs, linoleic (C18:2), linolenic (C18:3) and arachidonic acid (C20:4) inhibit KDR in a concentration-dependent manner in both strains, while the unsaturated lauric acid (C12:0) was ineffective. KDR from TRCs of S5B/Pl rats were significantly more sensitive to inhibition by all three PUFAs (10 microM) than were TRCs from O-M rats. We are currently investigating whether this differential responsiveness is due to (i) the relative affinity of the interaction between cis-PUFAs and the delayed rectifying K channels or (ii) the relative density of delayed rectifying K channels in the two rat strains. Whatever the mechanism, these data suggest an inverse correlation between peripheral gustatory sensitivity to PUFAs and the dietary preference for fat. This finding may provide insight into the mechanism for sensing dietary fat that allows the S5B rats to reduce fat intake on a high-fat diet and avoid the obesity which results when O-M rats eat a high-fat diet.
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PMID:Dietary fat preferences are inversely correlated with peripheral gustatory fatty acid sensitivity. 992 99

Polycystic ovary syndrome (PCOS) is a common endocrine disorder of women, characterized by hyperandrogenism and chronic anovulation. It is a leading cause of female infertility and is associated with polycystic ovaries, hirsutism, obesity, and insulin resistance. We tested a carefully chosen collection of 37 candidate genes for linkage and association with PCOS or hyperandrogenemia in data from 150 families. The strongest evidence for linkage was with the follistatin gene, for which affected sisters showed increased identity by descent (72%; chi(2) = 12.97; nominal P = 3.2 x 10(-4)). After correction for multiple testing (33 tests), the follistatin findings were still highly significant (P(c) = 0.01). Although the linkage results for CYP11A were also nominally significant (P = 0.02), they were no longer significant after correction. In 11 candidate gene regions, at least one allele showed nominally significant evidence for population association with PCOS in the transmission/disequilibrium test (chi(2) >/= 3.84; nominal P < 0.05). The strongest effect in the transmission/disequilibrium test was observed in the INSR region (D19S884; allele 5; chi(2) = 8.53) but was not significant after correction. Our study shows how a systematic screen of candidate genes can provide strong evidence for genetic linkage in complex diseases and can identify those genes that should have high (or low) priority for further study.
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PMID:Thirty-seven candidate genes for polycystic ovary syndrome: strongest evidence for linkage is with follistatin. 1041 66

Nonesterified fatty acids (NEFAs) are acutely liberated during lipolysis and are chronically elevated in pathological conditions, such as insulin resistance, hypertension, and obesity, which are known risk factors for atherosclerosis. The purpose of this study was to investigate the effect and mechanism of action of NEFAs on the epithelial growth factor (EGF) receptor (EGFR). In the ECV-304 endothelial cell line, unsaturated fatty acids triggered a time- and dose-dependent tyrosine phosphorylation of EGFR (polyunsaturated fatty acids [PUFAs] were the most active), whereas saturated FAs were inactive. Although less potent than PUFAs, oleic acid (OA) was used because it is prominent in the South European diet and is only slightly oxidizable (thus excluding oxidation derivatives). EGFR is activated by OA independent of any autocrine secretion of EGF or other related mediators. OA-induced EGFR autophosphorylation triggered EGFR signaling pathway activation (as assessed through coimmunoprecipitation of SH2 proteins such as SHC, GRB2, and SHP-2) and subsequent p42/p44 mitogen-activated protein kinase (as shown by the use of EGFR- deficient B82L and EGFR- transduced B82LK(+) cell lines). OA induced in vitro both autophosphorylation and activation of intrinsic tyrosine kinase of immunopurified EGFR, thus suggesting that EGFR is a primary target of OA. EGFR was also activated by mild surfactants, Tween-20 and Triton X-100, both in vitro (on immunopurified EGFR) and in intact living cells, thus indicating that EGFR is sensitive to amphiphilic molecules. These data suggest that EGFR is activated by OA and PUFAs, acts as a sensor for unsaturated fatty acids (and amphiphilic molecules), and is a potential transducer by which diet composition may influence vascular wall biology.
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PMID:Activation of epithelial growth factor receptor pathway by unsaturated fatty acids. 1055 35

We evaluated whether our previous reports of increased postmenopausal breast cancer risk with higher body mass index (BMI) or of reduced premenopausal and postmenopausal breast cancer risk with higher physical activity levels varied according to the tumor's estrogen receptor (ER) and progesterone receptor (PR) status. Participants enrolled in either of two population-based case-control studies in Los Angeles County, California: one of premenopausal women (ages < or = 40 years), and one of postmenopausal women (ages 55-64 years). Case participants were diagnosed for the first time with in situ or invasive breast cancer from 7/1/83 through 12/31/88 (premenopausal women) or from 3/1/87 through 12/31/89 (postmenopausal women). Joint ER/PR status was collected for 424 premenopausal and 760 postmenopausal case participants. The analysis included 714 premenopausal and 1091 postmenopausal age-matched, race-matched (white or Hispanic), parity-matched (premenopausal women only), and residential neighborhood-matched control participants. Among the postmenopausal women, obesity was associated with an increased odds of ER+/PR+ breast cancer (odds ratio, 2.45 for women in the highest versus the lowest body mass index quartile; 95% confidence interval, 1.73-3.47). Body mass index was associated with neither ER-/PR- tumors among the postmenopausal women nor with any ER/PR subgroup among the premenopausal women. For both premenopausal and postmenopausal women, higher recreational physical activity levels (> or = 17.6 MET-hours/week versus no activity) were associated with a 30-60% reduction in risk of nearly all ER/PR subtypes, although the associations were generally of borderline statistical significance. Examining these potentially modifiable breast cancer risk factors by tumor ER and PR status may provide us with greater insight into breast cancer etiology and the mechanisms underlying the risk factor associations.
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PMID:Body size, physical activity, and breast cancer hormone receptor status: results from two case-control studies. 1091 38


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