Recent advances in the role of cortisol and metabolic syndrome in age-related degenerative diseases

Martocchia, Antonio; Stefanelli, Manuela; Falaschi, Giulia Maria; Toussan, Lavinia; Ferri, Claudio; Falaschi, P.

doi:10.1007/s40520-015-0353-0

Cited by 41 publications

(24 citation statements)

References 58 publications

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“…S6). It has been suggested previously that cortisol levels or cortisol responses are increased during the aging process (45). Our data demonstrating that Foxa3 is induced by GCs combined with the evidence provided in our previous report indicating that Foxa3 levels increase in adipose tissues during aging (29) suggest a possible link between the effects of cortisol on Foxa3 levels in fat tissues and the induction of age-associated obesity.…”

Section: Discussionsupporting

confidence: 80%

Forkhead box A3 mediates glucocorticoid receptor function in adipose tissue

Mueller

2016

Proc. Natl. Acad. Sci. U.S.A.

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Glucocorticoids (GCs) are widely prescribed anti-inflammatory agents, but their chronic use leads to undesirable side effects such as excessive expansion of adipose tissue. We have recently shown that the forkhead box protein A3 (Foxa3) is a calorie-hoarding factor that regulates the selective enlargement of epididymal fat depots and suppresses energy expenditure in a nutritional- and age-dependent manner. It has been demonstrated that Foxa3 levels are elevated in adipose depots in response to high-fat diet regimens and during the aging process; however no studies to date have elucidated the mechanisms that control Foxa3’s expression in fat. Given the established effects of GCs in increasing visceral adiposity and in reducing thermogenesis, we assessed the existence of a possible link between GCs and Foxa3. Computational prediction analysis combined with molecular studies revealed that Foxa3 is regulated by the glucocorticoid receptor (GR) in preadipocytes, adipocytes, and adipose tissues and is required to facilitate the binding of the GR to its target gene promoters in fat depots. Analysis of the long-term effects of dexamethasone treatment in mice revealed that Foxa3 ablation protects mice specifically against fat accretion but not against other pathological side effects elicited by this synthetic GC in tissues such as liver, muscle, and spleen. In conclusion our studies provide the first demonstration, to our knowledge, that Foxa3 is a direct target of GC action in adipose tissues and point to a role of Foxa3 as a mediator of the side effects induced in fat tissues by chronic treatment with synthetic steroids.

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Section: Discussionsupporting

confidence: 80%

Forkhead box A3 mediates glucocorticoid receptor function in adipose tissue

Mueller

2016

Proc. Natl. Acad. Sci. U.S.A.

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“…10,15,18 In this review, special attention will be paid to CRP because it is the marker of inflammation that is most studied and most used for prediction of cardiovascular events.…”

Section: Inflammation: Can It Be Measured?mentioning

confidence: 99%

Síndrome metabólica, aterosclerose e inflamação: tríade indissociável?

et al. 2015

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Populations all over the world are increasingly inactive and are consuming increasing quantities of fats and sugars, which is generally linked to industrially processed foods. The consequences have rapidly manifest as an increase in overweight/obesity and in physiological and metabolic changes, such as the Metabolic Syndrome, which is a series of changes in glycemia, lipids and blood pressure. There is evidence of a close relationship between these changes and inflammatory processes, which can also be linked to oxidative stress. These conditions lead to the pathogenesis of vascular abnormalities or intensify metabolic processes that accompany the metabolic syndrome. The objective of this review is to compare the large number of bibliographic references that show correlations between components of the Metabolic Syndrome and increases in the mediators of inflammation. The publications reviewed were located using the Pubmed, Scopus, Lilacs and Scielo databases and the majority of the articles selected were published within the last 5 years.Keywords: metabolic syndrome ; arteriosclerosis; inflammation. ResumoObserva-se, nas populações mundiais, aumento do sedentarismo e aumento do consumo de gorduras e açúcares, sendo estes vinculados normalmente aos alimentos industrializados. A consequência disso rapidamente se manifestou no aumento do sobrepeso/obesidade e na instalação de alterações fisiológicas e metabólicas, como a Síndrome Metabólica, que é representada por alterações na glicemia, nos lipídeos e na pressão arterial. Há evidências de ligação estreita entre estas alterações e os processos inflamatórios, que também podem estar associados ao estresse oxidativo. Estas condições levam à patogênese das alterações vasculares ou intensificam os processos metabólicos que acompanham a Síndrome Metabólica. O objetivo desta revisão foi comparar as inúmeras referências literárias que mostram correlação entre os componentes da Síndrome Metabólica e o aumento dos mediadores de inflamação. Para isso, utilizou-se Pubmed, Scopus, Lilacs e Scielo como base de dados, sendo que os artigos selecionados dataram principalmente dos últimos cinco anos.Palavras-chave: síndrome metabólica; arteriosclerose; inflamação.

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“…Le cerveau joue un rôle central dans le contrôle des régulations métaboliques [40], et la présence de la 11βHSD1 dans l'hypothalamus suggère que cette enzyme pourrait jouer un rôle dans le contrôle de l'appétit [11]. La présence de la 11βHSD1 dans le cerveau est connue depuis au moins une vingtaine d'années [12], et son rôle dans certaines anomalies du fonctionnement cérébral est suspectée [41].…”

Section: Nouveaux Inhibiteurs De La 11βhsd1 En Développementunclassified

Cibler la voie métabolique du cortisol comme action thérapeutique dans le diabète de type 2

Scheen

2016

Médecine des Maladies Métaboliques

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RésuméLa 11β-hydroxystéroïde déshydrogénase de type 1 (11βHSD1) est une enzyme intervenant dans la transformation tissulaire de cortisone inactive en cortisol actif. Elle a été impliquée dans la physiopathologie de l'obésité abdominale, composante centrale du syndrome métabolique, une condition proche du syndrome de Cushing à certains égards. Des inhibiteurs synthétiques sélectifs de la 11βHSD1 ont été testés dans des essais préliminaires chez des patients diabétiques de type 2 ou hypertendus, mais avec des résultats mitigés, jugés insuffisants en comparaison des résultats obtenus avec d'autres classes de médicaments déjà disponibles. Une étude récente dans la stéatose hépatique a donné des résultats prometteurs chez des sujets en surpoids ou obèses non diabétiques. Alors que certains inhibiteurs de la 11βHSD1 ont été abandonnés, d'autres sont toujours en développement, ce qui témoigne de l'intérêt persistant pour cette approche thérapeutique innovante. Mots

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Recent advances in the role of cortisol and metabolic syndrome in age-related degenerative diseases

Cited by 41 publications

References 58 publications

Forkhead box A3 mediates glucocorticoid receptor function in adipose tissue

Forkhead box A3 mediates glucocorticoid receptor function in adipose tissue

Síndrome metabólica, aterosclerose e inflamação: tríade indissociável?

Cibler la voie métabolique du cortisol comme action thérapeutique dans le diabète de type 2

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