Nicholas M Morton

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The adverse metabolic consequences of obesity are best predicted by the quantity of visceral fat. Excess glucocorticoids produce visceral obesity and diabetes, but circulating glucocorticoid levels are normal in typical obesity. Glucocorticoids can be produced locally from inactive 11-keto forms through the enzyme 11beta hydroxysteroid dehydrogenase type 1(More)
Excess tissue glucocorticoid action may underlie the dyslipidemia, insulin resistance, and impaired glucose tolerance of the metabolic syndrome. 11beta-Hydroxysteroid dehydrogenase type 1 (11beta-HSD-1) catalyzes conversion of circulating inert 11-dehydrocorticosterone into active corticosterone, thus amplifying local intracellular glucocorticoid action,(More)
The metabolic syndrome (visceral obesity, insulin resistance, type 2 diabetes, and dyslipidemia) resembles Cushing's Syndrome, but without elevated circulating glucocorticoid levels. An emerging concept suggests that the aberrantly elevated levels of the intracellular glucocorticoid reamplifying enzyme 11 beta-hydroxysteroid dehydrogenase type 1 (11(More)
In obese humans and rodents there is increased expression of the key glucocorticoid (GC) regenerating enzyme, 11beta-hydroxysteroid dehydrogenase type 1 (11beta-HSD1), in adipose tissue. This increased expression appears to be of pathogenic importance because transgenic mice overexpressing 11beta-HSD1 selectively in adipose tissue exhibit a full metabolic(More)
Local glucocorticoid (GC) action depends on intracellular GC metabolism by 11beta-hydroxysteroid dehydrogenases (11betaHSDs). 11betaHSD1 activates GCs, while 11betaHSD2 inactivates GCs. Adipocyte-specific amplification of GCs through transgenic overexpression of 11betaHSD1 produces visceral obesity and the metabolic syndrome in mice. To determine whether(More)
The metabolic abnormalities found associated with high blood glucocorticoid levels (e.g. rare Cushing's syndrome) include insulin-resistance, visceral obesity, hypertension, dyslipidaemia and an increased risk of cardiovascular diseases. The same constellation of abnormalities is found in the highly prevalent idiopathic obesity/insulin-resistance(More)
OBJECTIVES: To investigate whether administration of leptin to rats during pregnancy and lactation affects placental 11β-hydroxysteroid dehydrogenase (11β-HSD2) activity and the susceptibility of their offspring to weight gain and insulin resistance.DESIGN: Pregnant rats fed on a low-protein diet were administered leptin or saline by subcutaneous minipump(More)
Leptin, encoded for by the mouse ob gene, regulates feeding behavior and energy metabolism. Its receptor (Ob-R) is encoded by the mouse diabetic (db) gene and is mutated in the db/db mouse so that it lacks the cytoplasmic domain. We show that the full-length leptin receptor (Ob-Rb), which is believed to transmit the leptin signal, is expressed in pancreatic(More)
Obesity is closely associated with the metabolic syndrome, a combination of disorders including insulin resistance, diabetes, dyslipidemia, and hypertension. A role for local glucocorticoid reamplification in obesity and the metabolic syndrome has been suggested. The enzyme 11beta-hydroxysteroid dehydrogenase type 1 (11beta-HSD1) regenerates active cortisol(More)
OBJECTIVES In ideopathic obesity, there is evidence that enhanced cortisol regeneration within abdominal subcutaneous adipose tissue may contribute to adiposity and metabolic disease. Whether the cortisol regenerating enzyme, 11beta-hydroxysteroid dehydrogenase type 1 (11betaHSD1), or glucocorticoid receptor (GRalpha) levels are altered in other adipose(More)