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

Am J Physiol Endocrinol Metab. 2011 Jun;300(6):E1076-84. doi: 10.1152/ajpendo.00531.2010. Epub 2011 Mar 15.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 11-beta-Hydroxysteroid Dehydrogenase Type 1 / biosynthesis*
  • 11-beta-Hydroxysteroid Dehydrogenase Type 1 / genetics
  • Adipose Tissue / enzymology*
  • Adipose Tissue / physiology*
  • Adiposity
  • Animals
  • Body Composition / physiology*
  • Corticosterone / metabolism
  • Diet*
  • Eating / drug effects
  • Fatty Acids / pharmacology
  • Fatty Acids, Monounsaturated / pharmacology
  • Fatty Acids, Unsaturated / pharmacology
  • Feces / chemistry
  • Gene Expression / drug effects
  • Homeostasis / drug effects
  • Homeostasis / physiology
  • Insulin Resistance / physiology
  • Liver / drug effects
  • Liver / enzymology
  • Male
  • Mice
  • Mice, Inbred C57BL
  • RNA / biosynthesis
  • RNA / genetics
  • Receptors, Glucocorticoid / biosynthesis
  • Receptors, Glucocorticoid / genetics
  • Reverse Transcriptase Polymerase Chain Reaction
  • Weight Gain / drug effects

Substances

  • Fatty Acids
  • Fatty Acids, Monounsaturated
  • Fatty Acids, Unsaturated
  • Receptors, Glucocorticoid
  • RNA
  • 11-beta-Hydroxysteroid Dehydrogenase Type 1
  • Corticosterone