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

Tak Yung Man, Zoi Michailidou, Adnan Gokcel, Lynne Ramage, Karen E. Chapman, Christopher J. Kenyon, Jonathan R. Seckl, Nicholas M. Morton

Research output: Contribution to journalArticlepeer-review

Abstract / Description of output

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

Keywords / Materials (for Non-textual outputs)

  • 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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