title: Effects of proportions of dietary macronutrients on glucocorticoid metabolism in diet-induced obesity in rats.
abstract: Tissue glucocorticoid levels in the liver and adipose tissue are regulated by regeneration of inactive glucocorticoid by 11beta-hydroxysteroid dehydrogenase type 1 (11beta-HSD1) and inactivation by 5alpha- and 5beta-reductases. A low carbohydrate diet increases hepatic 11beta-HSD1 and reduces glucocorticoid metabolism during weight loss in obese humans. We hypothesized that similar variations in macronutrient proportions regulate glucocorticoid metabolism in obese rats. Male Lister Hooded rats were fed an obesity-inducing ad libitum 'Western' diet (37% fat, n = 36) for 22 weeks, then randomised to continue this diet (n = 12) or to switch to either a low carbohydrate (n = 12) or a moderate carbohydrate (n = 12) diet for the final 8 weeks. A parallel lean control group were fed an ad libitum control diet (10% fat, n = 12) throughout. The low and moderate carbohydrate diets decreased hepatic 11beta-HSD1 mRNA compared with the Western diet (both 0.7+/-0.0 vs 0.9+/-0.1 AU; p<0.01), but did not alter 11beta-HSD1 in adipose tissue. 5Alpha-reductase mRNA was increased on the low carbohydrate compared with the moderate carbohydrate diet. Compared with lean controls, the Western diet decreased 11beta-HSD1 activity (1.6+/-0.1 vs 2.8+/-0.1 nmol/mcg protein/hr; p<0.001) and increased 5alpha-reductase and 5beta-reductase mRNAs (1.9+/-0.3 vs 1.0+/-0.2 and 1.6+/-0.1 vs 1.0+/-0.1 AU respectively; p<0.01) in the liver, and reduced 11beta-HSD1 mRNA and activity (both p<0.01) in adipose tissue. Although an obesity-inducing high fat diet in rats recapitulates the abnormal glucocorticoid metabolism associated with human obesity in liver (but not in adipose tissue), a low carbohydrate diet does not increase hepatic 11beta-HSD1 in obese rats as occurs in humans.
authors.affiliation: Centre for Cardiovascular Sciences, Queen's Medical Research Institute, University of Edinburgh, Edinburgh, United Kingdom. roland.stimson@ed.ac.uk
authors.forename: Roland H
authors.initials: RH
authors.lastname: Stimson
authors.forename: Gerald E
authors.initials: GE
authors.lastname: Lobley
authors.forename: Ioanna
authors.initials: I
authors.lastname: Maraki
authors.forename: Nicholas M
authors.initials: NM
authors.lastname: Morton
authors.forename: Ruth
authors.initials: R
authors.lastname: Andrew
authors.forename: Brian R
authors.initials: BR
authors.lastname: Walker
mesh_terms: D013741:3-Oxo-5-alpha-Steroid 4-Dehydrogenase / Q000235:genetics; D000818:Animals; D004032:Diet; D005938:Glucocorticoids / Q000378:metabolism*; D009765:Obesity / Q000209:etiology / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics; D051381:Rats
chemical_list: D005938:Glucocorticoids; D012333:RNA, Messenger; D013741:3-Oxo-5-alpha-Steroid 4-Dehydrogenase