High fructose diets increase 11β-hydroxysteroid dehydrogenase type 1 in liver and visceral adipose in rats within 24-h exposure.
The increased prevalence of overweight and obesity in the United States during the past three decades coincides with a trend of increased sugar intake, especially fructose, leading to speculation that the two trends may be linked. The enzyme 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1), that regulates intracellular tissue-specific glucocorticoid levels, is increased in adipose and suppressed in liver of obese humans and animals. Hexose-6-phosphate dehydrogenase (H6PDH) is colocalized with 11β-HSD1 and generates nicotinamide adenosine dinucleotide phosphate, the required cofactor for 11β-HSD1 reductase activity that converts inert glucocorticoid metabolite into active hormone. We examined the acute effects of ad lib access to 16% solutions of sucrose, fructose, or glucose and chow and water. Diets high in fructose, but not glucose or sucrose increased 11β-HSD1 mRNA within 24 h in liver and adipose by greater than two- and threefold, respectively (P ≤ 0.05). After 1 week, hepatic 11β-HSD1 mRNA and protein were suppressed by >60% in all sugar-fed groups, a phenomenon not previously reported in the absence of obesity. Sucrose- and fructose-fed rats had higher plasma triglycerides than did control or glucose-fed rats at both 24 h and 1 week (P ≤ 0.02), consistent with previously reported effects of fructose on lipid metabolism. We conclude that high-sugar diets initiate glucocorticoid dysregulation associated with obesity prior to the onset of phenotypic changes, and that high fructose diets specifically induce changes in 11β-HSD1 within 24-h exposure.
Department of Nutrition and Food Science, University of Maryland, College Park, Maryland, USA.
Edra
E
London
Thomas W
TW
Castonguay
D043205:11-beta-Hydroxysteroid Dehydrogenase Type 1 / Q000378:metabolism*; D000818:Animals; D004032:Diet; D005632:Fructose / Q000494:pharmacology*; D050152:Intra-Abdominal Fat / Q000201:enzymology* / Q000473:pathology; D050356:Lipid Metabolism; D008099:Liver / Q000201:enzymology* / Q000473:pathology; D008297:Male; D009765:Obesity / Q000201:enzymology* / Q000473:pathology; D051381:Rats; D017207:Rats, Sprague-Dawley; D013549:Sweetening Agents / Q000494:pharmacology*; D013997:Time Factors
D013549:Sweetening Agents; D005632:Fructose; D043205:11-beta-Hydroxysteroid Dehydrogenase Type 1