A Glucocorticoid Receptor Gene Marker Is Associated with Abdominal Obesity, Leptin, and Dysregulation of the Hypothalamic‐Pituitary‐Adrenal Axis

Rosmond, Roland; Chagnon, Yvon C.; Holm, Göran; Chagnon, Monique; Pérusse, Louis; Lindell, Kajsa; Carlsson, Björn; Bouchard, Claude; Björntorp, Per

doi:10.1038/oby.2000.24

Cited by 216 publications

(177 citation statements)

References 28 publications

(47 reference statements)

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“…There is growing evidence that both stress and glucocorticoids contribute to the etiology of cardiovascular disease; however, the role of glucocorticoids in the stress response has long been a matter of debate (1,3,5,13,15,28,30,31,35,36,38,39,42,48,49,52,58,61,65,67,68,70,71). Recent research has led to the general hypothesis that stress-induced increases in glucocorticoids act in the brain to prepare the organism for future events (12,52).…”

Section: Perspectivesmentioning

confidence: 99%

“…Acute stress rapidly increases blood pressure, heart rate, plasma glucocorticoid concentration, and blood glucose levels (8), while chronic or repeated stress is associated with increases in baseline blood pressure and glucocorticoids (17). Chronically elevated glucocorticoids increase morbidity and mortality from cardiovascular disease and alterations in the glucocorticoid receptor (GR), and in glucocorticoid metabolizing enzymes are associated with hypertension and cardiovascular disease in humans (28,30,35,36,39,48,49,61,65,67,70,71). Thus, chronic stress-induced elevations in glucocorticoids likely contribute to the adverse effects of stress on cardiovascular health.…”

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confidence: 99%

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Chronic blockade of hindbrain glucocorticoid receptors reduces blood pressure responses to novel stress and attenuates adaptation to repeated stress

Bechtold

Patel²,

Hochhaus³

et al. 2009

American Journal of Physiology-Regulatory, Integrative and Comp

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Exogenous glucocorticoids act within the hindbrain to enhance the arterial pressure response to acute novel stress. Here we tested the hypothesis that endogenous glucocorticoids act at hindbrain glucocorticoid receptors (GR) to augment cardiovascular responses to restraint stress in a model of stress hyperreactivity, the borderline hypertensive rat (BHR). A 3-to 4-mg pellet of the GR antagonist mifepristone (Mif) was implanted over the dorsal hindbrain (DHB) in WistarKyoto (WKY) and BHRs. Control pellets consisted of either sham DHB or subcutaneous Mif pellets. Rats were either subjected to repeated restraint stress (chronic stress) or only handled (acute stress) for 3-4 wk, then all rats were stressed on the final day of the experiment. BHR showed limited adaptation of the arterial pressure response to restraint, and DHB Mif significantly (P Յ 0.05) attenuated the arterial pressure response to restraint in both acutely and chronically stressed BHR. In contrast, WKY exhibited a substantial adaptation of the pressure response to repeated restraint that was significantly reversed by DHB Mif. DHB Mif and chronic stress each significantly increased baseline plasma corticosterone concentration and adrenal weight and reduced the corticosterone response to stress in all rats. We conclude that endogenous corticosterone acts via hindbrain GR to enhance the arterial pressure response to stress in BHR, but to promote the adaptation of the arterial pressure response to stress in normotensive rats. Endogenous corticosterone also acts in the hindbrain to restrain corticosterone at rest but to maintain the corticosterone response to stress in both BHR and WKY rats. corticosterone; brain; nucleus of the solitary tract; hypothalamicpituitary-adrenal axis; chronic stress EXAGGERATED CARDIOVASCULAR responses to acute stress and chronic stress increase the risk for hypertension and cardiovascular disease (1,3,13,15,31,38,42,58,68). Acute stress rapidly increases blood pressure, heart rate, plasma glucocorticoid concentration, and blood glucose levels (8), while chronic or repeated stress is associated with increases in baseline blood pressure and glucocorticoids (17). Chronically elevated glucocorticoids increase morbidity and mortality from cardiovascular disease and alterations in the glucocorticoid receptor (GR), and in glucocorticoid metabolizing enzymes are associated with hypertension and cardiovascular disease in humans (28,30,35,36,39,48,49,61, 65,67,70,71). Thus, chronic stress-induced elevations in glucocorticoids likely contribute to the adverse effects of stress on cardiovascular health.The mechanisms by which glucocorticoids modulate cardiovascular stress responses are not fully understood. A review by Sapolsky et al. (52) concluded that glucocorticoids act permissively to enhance the arterial pressure response to many physical stressors, in part by supporting the peripheral effects of catecholamines. Other studies indicate that chronic, systemic elevations in glucocorticoids enhance cardiovascular and catecholamine re...

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Section: Perspectivesmentioning

confidence: 99%

mentioning

confidence: 99%

Chronic blockade of hindbrain glucocorticoid receptors reduces blood pressure responses to novel stress and attenuates adaptation to repeated stress

Bechtold

Patel²,

Hochhaus³

et al. 2009

American Journal of Physiology-Regulatory, Integrative and Comp

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“…The interaction between glucocorticoid and insulin is a very important signal for regulating long-term energy metabolism [64]. In particular, NR3C1, the downstream gene of HSD11B2, has been reported to be associated with glucocorticoid resistance, eating disorder and obesity [58,66]. Therefore, it is highly possible that HSD11B2 is related to eating disorder.…”

Section: Discussionmentioning

confidence: 99%

EDdb: A web resource for eating disorder and its application to identify an extended adipocytokine signaling pathway related to eating disorder

Zhao

2013

Sci. China Life Sci.

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Eating disorder is a group of physiological and psychological disorders affecting approximately 1% of the female population worldwide. Although the genetic epidemiology of eating disorder is becoming increasingly clear with accumulated studies, the underlying molecular mechanisms are still unclear. Recently, integration of various high-throughput data expanded the range of candidate genes and started to generate hypotheses for understanding potential pathogenesis in complex diseases. This article presents EDdb (Eating Disorder database), the first evidence-based gene resource for eating disorder. Fifty-nine experimentally validated genes from the literature in relation to eating disorder were collected as the core dataset. Another four datasets with 2824 candidate genes across 601 genome regions were expanded based on the core dataset using different criteria (e.g., protein-protein interactions, shared cytobands, and related complex diseases). Based on human protein-protein interaction data, we reconstructed a potential molecular sub-network related to eating disorder. Furthermore, with an integrative pathway enrichment analysis of genes in EDdb, we identified an extended adipocytokine signaling pathway in eating disorder. Three genes in EDdb (ADIPO (adiponectin), TNF (tumor necrosis factor) and NR3C1 (nuclear receptor subfamily 3, group C, member 1)) link the KEGG (Kyoto Encyclopedia of Genes and Genomes) "adipocytokine signaling pathway" with the BioCarta "visceral fat deposits and the metabolic syndrome" pathway to form a joint pathway. In total, the joint pathway contains 43 genes, among which 39 genes are related to eating disorder. As the first comprehensive gene resource for eating disorder, EDdb (http://eddb.cbi.pku.edu.cn) enables the exploration of gene-disease relationships and cross-talk mechanisms between related disorders. Through pathway statistical studies, we revealed that abnormal body weight caused by eating disorder and obesity may both be related to dysregulation of the novel joint pathway of adipocytokine signaling. In addition, this joint pathway may be the common pathway for body weight regulation in complex human diseases related to unhealthy lifestyle. eating disorder, database, adipocytokine signaling pathway, pathway analysis Citation:Zhao M, Li X M, Qu H. EDdb: A web resource for eating disorder and its application to identify an extended adipocytokine signaling pathway related to eating disorder.

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“…; associated with cortisol levels (BclI) 34,35 ADRA2A Chromosome 10q25 ADRA2ADraI 6.3/6.3+6.3/6.7 (30%) 6.7/6.7 (70%) Unknown (DraI)…”

Section: Discussionmentioning

confidence: 99%

Contribution of several candidate gene polymorphisms in the determination of adiposity changes: results from the Québec Family Study

et al. 2007

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Background: Several candidate genes have been associated with obesity, but very few studies have tested more than one gene simultaneously. Methods: In this study, 15 polymorphisms in 10 candidate genes of obesity were tested for association with changes in adiposity measured over a period of 6-10 years in a maximum of 332 adult subjects with a wide range of adiposity (17.5obody mass index (BMI)o55.6 kg/m 2 ) from the Québec Family Study. Stepwise regression models were used to identify the combination of genes explaining changes in adiposity after adjustment for age (initial value), gender, initial value of the adiposity variable and duration of follow-up. Analyses were carried out in the whole sample and repeated while stratifying on age (o40 and X40 years). Results: In the whole sample, the variance in age-related adiposity changes explained by the candidate gene polymorphisms ranged from 3.1% (BMI, Po0.05) to 8.5% (fat mass (FM), Pp0.0005). The genes retained in the prediction model for changes in FM were leptin (Pp0.05), guanine nucleotide binding protein b3 (Pp0.05), adrenergic receptor b3 (Pp0.05), neuromedin b (Pp0.05) and peroxisome proliferator-activated receptor-g2 (Pp0.10). The effects of the genes were significant in both age groups, but the genes contributing to adiposity changes were different and their effects were stronger in the younger than in the older age group. Conclusion: This study suggests that models including genetic information from several candidate gene polymorphisms can significantly contribute to the changes in adiposity over time, that different genes may act at different ages and that genetic information could be useful for the identification of individuals at high risk for gaining body fat over time.

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A Glucocorticoid Receptor Gene Marker Is Associated with Abdominal Obesity, Leptin, and Dysregulation of the Hypothalamic‐Pituitary‐Adrenal Axis

Cited by 216 publications

References 28 publications

Chronic blockade of hindbrain glucocorticoid receptors reduces blood pressure responses to novel stress and attenuates adaptation to repeated stress

Chronic blockade of hindbrain glucocorticoid receptors reduces blood pressure responses to novel stress and attenuates adaptation to repeated stress

EDdb: A web resource for eating disorder and its application to identify an extended adipocytokine signaling pathway related to eating disorder

Contribution of several candidate gene polymorphisms in the determination of adiposity changes: results from the Québec Family Study

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