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Dietary manipulation reveals an unexpected inverse relationship between fat mass and adipose 11β-hydroxysteroid dehydrogenase type 1

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    Rights statement: Published in final edited form as: Am J Physiol Endocrinol Metab. 2011 June ; 300(6): E1076–E1084. doi:10.1152/ajpendo.00531.2010.

    Accepted author manuscript, 1.58 MB, PDF document

Original languageEnglish
Pages (from-to)E1076-E1084
Number of pages9
JournalAmerican Journal of Physiology - Endocrinology And Metabolism
Issue number6
Publication statusPublished - Jun 2011


Increased dietary fat intake is associated with obesity, insulin resistance, and metabolic disease. In transgenic mice, adipose tissue-specific overexpression of the glucocorticoid-amplifying enzyme 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) exacerbates high-fat (HF) diet-induced visceral obesity and diabetes, whereas 11β-HSD1 gene knockout ameliorates this, favoring accumulation of fat in nonvisceral depots. Paradoxically, in normal mice HF diet-induced obesity (DIO) is associated with marked downregulation of adipose tissue 11β-HSD1 levels. To identify the specific dietary fats that regulate adipose 11β-HSD1 and thereby impact upon metabolic disease, we either fed mice diets enriched (45% calories as fat) in saturated (stearate), monounsaturated (oleate), or polyunsaturated (safflower oil) fats ad libitum or we pair fed them a low-fat (11%) control diet for 4 wk. Adipose and liver mass and glucocorticoid receptor and 11β-HSD1 mRNA and activity levels were determined. Stearate caused weight loss and hypoinsulinemia, partly due to malabsorption, and this markedly increased plasma corticosterone levels and adipose 11β-HSD1 activity. Oleate induced pronounced weight gain and hyperinsulinemia in association with markedly low plasma corticosterone and adipose 11β-HSD1 activity. Weight gain and hyperinsulinemia was less pronounced with safflower compared with oleate despite comparable suppression of plasma corticosterone and adipose 11β-HSD1. However, with pair feeding, safflower caused a selective reduction in visceral fat mass and relative insulin sensitization without affecting plasma corticosterone or adipose 11β-HSD1. The dynamic depot-selective relationship between adipose 11β-HSD1 and fat mass strongly implicates a dominant physiological role for local tissue glucocorticoid reactivation in fat mobilization.

    Research areas

  • 11-beta-Hydroxysteroid Dehydrogenase Type 1, Adipose Tissue, Adiposity, Animals, Body Composition, Corticosterone, Diet, Eating, Fatty Acids, Fatty Acids, Monounsaturated, Fatty Acids, Unsaturated, Feces, Gene Expression, Homeostasis, Insulin Resistance, Liver, Male, Mice, Mice, Inbred C57BL, RNA, Receptors, Glucocorticoid, Reverse Transcriptase Polymerase Chain Reaction, Weight Gain

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