11 beta-Hydroxysteroid dehydrogenase type 1: relevance of its modulation in the pathophysiology of obesity, the metabolic syndrome and type 2 diabetes mellitus

• Tipo: Outra Publicação em Revista Científica Internacional
• Data: 2012

Autores

Pereira, CD (Autor) Outra; Azevedo, I (Autor) Outra; Monteiro, R (Autor) FMUP; Martins, MJ (Autor) FMUP

Revista

Título: Diabetes, Obesity and Metabolism

Vol. 14

Páginas: 869-881

ISSN: 1462-8902

Editora: Wiley-Blackwell

Indexação

ISI Web of Knowledge - 69 Citações

Scopus - 79 Citações

Classificação Científica

FOS: Ciências médicas e da saúde > Medicina clínica

Outras Informações

ID Authenticus: P-002-53N

DOI: 10.1111/j.1463-1326.2012.01582.x

Abstract (EN): Recent evidence strongly argues for a pathogenic role of glucocorticoids and 11 beta-hydroxysteroid dehydrogenase type 1 (11 beta-HSD1) in obesity and the metabolic syndrome, a cluster of risk factors for atherosclerotic cardiovascular disease and type 2 diabetes mellitus (T2DM) that includes insulin resistance (IR), dyslipidaemia, hypertension and visceral obesity. This has been partially prompted not only by the striking clinical resemblances between the metabolic syndrome and Cushing's syndrome (a state characterized by hypercortisolism that associates with metabolic syndrome components) but also from monogenic rodent models for the metabolic syndrome (e. g. the leptin-deficient ob/ob mouse or the leptin-resistant Zucker rat) that display overall increased secretion of glucocorticoids. However, systemic circulating glucocorticoids are not elevated in obese patients and/or patients with metabolic syndrome. The study of the role of 11 beta-HSD system shed light on this conundrum, showing that local glucocorticoids are finely regulated in a tissue-specific manner at the pre-receptor level. The system comprises two microsomal enzymes that either activate cortisone to cortisol (11 beta-HSD1) or inactivate cortisol to cortisone (11 beta-HSD2). Transgenic rodent models, knockout (KO) for HSD11B1 or with HSD11B1 or HSD11B2 overexpression, specifically targeted to the liver or adipose tissue, have been developed and helped unravel the currently undisputable role of the enzymes in metabolic syndrome pathophysiology, in each of its isolated components and in their prevention. In the transgenic HSD11B1 overexpressing models, different features of the metabolic syndrome and obesity are replicated. HSD11B1 gene deficiency or HSD11B2 gene overexpression associates with improvements in the metabolic profile. In face of these demonstrations, research efforts are now being turned both into the inhibition of 11 beta-HSD1 as a possible pharmacological target and into the role of dietary habits on the establishment or the prevention of the metabolic syndrome, obesity and T2DM through 11 beta-HSD1 modulation. We intend to review and discuss 11 beta-HSD1 and obesity, the metabolic syndrome and T2DM and to highlight the potential of its inhibition for therapeutic or prophylactic approaches in those metabolic diseases.

Idioma: Inglês

Tipo (Avaliação Docente): Científica

Nº de páginas: 13