Hormonal
Elevated local glucocorticoid activity in adipose tissue, driven by increased 11beta-HSD1 enzyme expression, causes visceral obesity and metabolic syndrome features despite normal circulating cortisol levels.
Visceral obesity is driven by local enzyme activity (11beta-HSD1) converting inactive steroids into active cortisol within belly fat, not necessarily by high blood cortisol. This suggests that therapies targeting this specific enzyme in adipose tissue could treat metabolic syndrome and visceral obesity without affecting systemic hormone levels.
11beta-hydroxysteroid dehydrogenase type 1 (11beta-HSD1), at least in mature adipocytes and hepatocytes, converts inactive circulating 11-keto steroids into active glucocorticoids, amplifying local glucocorticoid action. 11beta-HSD1 is elevated in adipose tissue in obese humans and rodents, suggesting that adipose tissue glucocorticoid excess may explain the conundrum.
Why this rating
Supported by multiple lines of evidence including human observational studies, transgenic mouse models (overexpression and knockout), and biochemical assays.
Source
Glucocorticoids and 11beta-Hydroxysteroid Dehydrogenase in Adipose Tissue
Jonathan R. Seckl · Recent Progress in Hormone Research · 2004
DOI 10.1210/rp.59.1.359
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